AMNIOTIC FLUID STEM CELLS

MESENCHIMAL STEM CELLS IN HUMAN APPLICATION

AMNIOTIC FLUID STEM CELLS

MESENCHIMAL STEM CELLS IN HUMAN APPLICATION







A SCIENTIFIC PAPERS REVIEW





Introduction
This issue rappresents a collection of the most important articles related on amniotic fluid stem cells, mesenchymal stem cells and clinical trials. The review includes articles published in 2009, 2008, 2007 and 2006.The summary carries title, scientific paper, publication date, authors and promoting organization. The abstract of each article is reported.

In particular, among clinical trials articles we would like to point out the following:

o “Application of stem cells in bone repair.” (n. 65)
o “Mesenchymal stem cells for treatment of steroid-resistant, severe, acutegraft-versus-host disease: a phase II study.” (n.73)
o “Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy.” (n.74)
o “Dental pulp stem cells: a promising tool for bone regeneration.” (n. 78)
o “Biologic characteristics of mesenchymal stromal cells and their clinical applications in pediatric patients.” (n.80)
o “Therapeutic applications of mesenchymal stromal cells.” (n.86)
o “Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study” (n.97)

Among articles regarding amniotic fluid stem cells:
o “Human Amniotic Fluid Mesenchymal Stem Cells in combination with hyperbaric oxygen augment peripheral nerve regeneration” (n.14)
o “Production of hepatocyte-like cells from human amnion” (n.35)
o “Neuronal characteristics of amniotic fluid derived cells after adenoviral transformation” (n.39)
o “Non-invasive longitudinal tracking of human amniotic fluid stem cells in the mouse heart.” (n.40)
o “Human amniotic fluid stem cells can integrate and differentiate into epithelial lung lineages.” (n.49)
o “High transduction efficiency of human amniotic fluid stem cells mediated by adenovirus vectors.” (n.55)
o “Differentiation of human amniotic fluid stem cells into cardiomyocytes through embryonic body formation” (n.57)
o “Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application” (n.81)
o “Chondrogenic differentiation of amniotic fluid-derived stem cells.” (n.90)
o “Mesenchymal cells from human amniotic fluid survive and migrate after transplantation into adult rat brain.” (n.94)

Mesenchymal stem cells articles :
o “Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy” (n.1)
o “Transplantation of mesenchymal stem cells within a poly(lactide-co-{varepsiolon}-caprolactone) scaffold improves cardiac function in a rat myocardial infarction model” (n.3)
o “Hyperthermia-treated msenchymal stem cells exert antitumor effects on human carcinoma cell line” (n.15)
o “Human adipose-derived mesenchymal stem cells reduce inflammatory and T-cell responses and induce regulatoru T cells in vitro in rheumatoid arthritis” (n. 28)
o “Contribution of stem cells to kidney repair” (n.34)
o “Potential role of culture mediums for successful isolation and neuronal differentiation of amniotic fluid stem cells.” (n.61)
o “Cryopreserved amniotic fluid-derived cells: a lifelong autologous fetal stem cell source for heart valve tissue engineering” (n.63)
o “Preclinical regulatory validation of a 3-stage amniotic mesenchymal stem cell manufacturing protocol.” (n. 68)
o “Characterization of human amniotic fluid stem cells and their pluripotential capability” (n.83)

At the end some comparative studies:
o “Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells” (n.37)
o “Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: a comparative study.” (n.51)
o “Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells.” (n.88)



TRADUZIONE IN ITALIANO: Introduzione
In questo fascicolo sono stati raccolti gli articoli più significativi relativi alle cellule staminali da liquido amniotico, alle cellule staminali mesenchimali e ai loro trials clinici.
La rassegna copre a ritroso i primi mesi del 2009, l’anno appena trascorso, il 2007 e il 2006; l’indice generale riporta i titoli delle ricerche, la rivista scientifica sulla quale è stato pubblicato, la data di pubblicazione, gli autori e l’ente promotore.
Per ogni articolo viene poi riportato l’abstrat. Tra quelli raccolti, si evidenziano nei trials clinici i seguenti articoli:
o “Applicazione delle cellule staminali per la riparazione ossea” (n. 65)
o “Cellule staminali mesenchimali per il trattamento di pazienti con resistenza steroidea e malattia da rigetto nei confronti dell’ospite: studi di fase 2” (n.73)
o “La terapia cellulare mediante staminali mesenchimali ritarda la progressione del deficit neurologico in pazienti con atrofia del sistema multiplo” (n.74)
o “Cellule staminali dalla polpa dentaria: un promettente “attrezzo” per la rigenerazione ossea” (n. 78)
o “Caratteristiche biologiche delle cellule stromali mesenchimali ed applicazioni cliniche in pazienti pediatrici” (n.80)
o “Applicazioni terapeutiche delle cellule stromali mesenchimali” (n.86)
o “Come la terapia con le cellule staminali mesenchimali è di aiuto per i pazienti con sclerosi multipla?” (n.97)
Inoltre tra le pubblicazioni riguardo le cellule staminali da liquido amniotico e della membrana amniotica, si segnalano:
o “Le cellule staminali mesenchimali del liquido amniotico in combinazione con ossigeno iperbarico aumentano la rigenerazione nervosa periferica” (n.14)
o “Produzione di cellule simil-epatocitiche dall’amnio umano” (n.35)
o “Caratteristiche neuronali delle cellule derivanti dal liquido amniotico dopo trasformazione adenovirale” (n.39)
o “Monitoraggio longitudinale non invasivo delle cellule staminali provenienti dal liquido amniotico nel cuore di topo.” (n.40)
o “Le cellule staminali da liquido amniotico possono integrarsi e differenziarsi nelle linee epiteliali polmonari.” (n.49)
o “Alta efficienza di trasduzione delle cellule staminali del liquido amniotico mediata da vettori di adenovirus.” (n.55)
o “Differenziazione in cardiomiociti delle cellule staminali del liquido amniotico attraverso la formazione di corpi embrionici” (n.57)
o “Cellule stromali mesenchimali multipotenti dal liquido amniotico: una solida prospettiva per l’applicazione clinica” (n.81)
o “Differenziazione condrogenica delle cellule staminali derivanti dal liquido amniotico.” (n.90)
o “Le cellule mesenchimali del liquido amniotico sopravvivono e migrano dopo trapianto nel cervello di ratto adulto.” (n.94)
Tra i numerosi articoli delle cellule staminali mesenchimali sono da evidenziare:
o “Cellule staminali mesenchimali in tessuto connettivo ingegnerizzato e nella medicina rigenerativa: applicazioni nella riparazione della cartilagene e nella terapia dell’osteoartrite.” (n.1)
o “Il trapianto di cellule staminali mesenchimali con una struttura di PLCL aumenta la funzionalità cardiaca nel cuore infartuato di ratto” (n.3)
o “Cellule staminali mesenchimali trattate al calore esercitano un effetto anitumorale nella linea cellulare di carcinoma umano” (n.15)
o “Le cellule staminali mesenchimali umane derivanti dal tessuto adiposo riducono l’infiammazione, la risposta dei linfociti T e inducono la regolazione delle cellule T in vitro” (n. 28)
o “Contributo delle cellule staminali nella riparazione renale” (n.34)
o “Ruolo potenziale dei miediums di cultura nell’isolamento e nella differenziazione neuronale delle cellule staminali di liquido amniotico” (n.61)
o “Crioconservazione di cellule amniotiche: una fonte di cellule staminali fetali per tessuti ingegnerizzati delle valvole cardiache” (n.63)
o “Validazione preclinica di stadio 3 del protocollo di manipolazione delle cellule staminali mesenchimali amniotiche” (n. 68)
o “Caratterizzazione delle cellule staminali da liquido amniotico e loro capacità di pluripotenza” (n.83)
Infine, alcuni studi comparativi:
o “Comparazione delle cellule staminali mesenchimali della placenta con le cellule staminali mesenchimali del midollo osseo” (n.37)
o “Caratterizzazione e differenziazione epatogenica delle cellule staminali mesenchimali del liquido amniotico e del midollo osseo umano: uno studio comparativo.” (n.51)
o “Caratterizzazione molecolare e proteo mica delle cellule staminali mesenchimali umane derivanti dal liquido amniotico: comparazione con le cellule staminali mesenchimali del midollo osseo.” (n.88)





























1. Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy.
Histol Histopathol. 2009 Mar;
Mobasheri A, Csaki C, Clutterbuck AL, Rahmanzadeh M, Shakibaei M.
Division of Veterinary Medicine, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom.

2. Effect of mesenchymal stem cells and platelet-rich plasma on the healing of standardized bone defets in the alveolar ridge: a comparative histomorphometric study in minipigs
J Oral Maxillofac Surg. 2009 Feb;
Pieri F, Lucarelli E, Corinaldesi G, Fini M, Aldini NN, Giardino R, Donati D, Marchetti C.
Department of Odontostomatological Sciences, University of Bologna, Bologna, Italy.
3. Transplantation of mesenchymal stem cells within a poly(lactide-co-{varepsiolon}-caprolactone) scaffold improves cardiac function in a rat myocardial infarction model
Eur J Heart Fail. 2009 Feb,
Jin J, Jeong SI, Shin YM, Lim KS, Shin HS, Lee YM, Koh HC, Kim KS.
Division of Cardiology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-ku, Seoul 133-791, South Korea.

4. Mesenchymal stem remain host-derived independent of the source of the stem-cell graft and conditioning regimen used
Transplantation. 2009 Jan 27;
Bartsch K, Al-Ali H, Reinhardt A, Franke C, Hudecek M, Kamprad M, Tschiedel S, Cross M, Niederwieser D, Gentilini C.
Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany.
5. Evaluation of the osteogenic potential and vascilarization of 3D poly(3)hydroxybutyrate scaffolds subcutaneously implanted in nude rats.
J Biomed Mater Res A. 2009 Jan 23.
Rentsch C, Rentsch B, Breier A, Hofmann A, Manthey S, Scharnweber D, Biewener A, Zwipp H.
Department of Trauma and Reconstructive Surgery, University Hospital Carl Gustav Carus Dresden, Fetscher Strasse 74, 01307 Dresden, Germany.

6. Mesenchymal progenitor cells derived from traumatized human muscle
J Tissue Eng Regen Med. 2009 Jan 23.
Jackson WM, Aragon AB, Djouad F, Song Y, Koehler SM, Nesti LJ, Tuan RS.
Cartilage Biology and Orthopaedic Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.

7. Perfusion affects the tissue developmental patterns of human mesenchymal stem cells in 3D scaffolds.
J Cell Physiol. 2009 Jan 23.
Zhao F, Grayson WL, Ma T, Irsigler A.
Department of Chemical and Biomedical Engineering, Florida State University, Tallahassee, Florida.

8. Secretome from mesenchymal stem cells induces angiogenesis via Cyr61
J Cell Physiol. 2009 Jan 23.
Estrada R, Li N, Sarojini H, An J, Lee MJ, Wang E.
Gheens Center on Aging, University of Louisville School of Medicine, Louisville, Kentucky.
9. Effect of Ceramide on Mesenchymal Stem Cell Differentiation Toward Adipocytes
Appl Biochem Biotechnol. 2009 Jan 23.
Xu F, Yang CC, Gomillion C, Burg KJ.
Institute of Biological Interfaces of Engineering, Department of Bioengineering, College of Science and Engineering, Clemson University, Clemson, SC, 29634, USA.
10. Expression of a functional epidermal growth factor receptor on human adipose-derived mesenchymal stem cells and its signaling mechanism
Eur J Cell Biol. 2009 Jan 22.
Baer PC, Schubert R, Bereiter-Hahn J, Plößer M, Geiger H.
Division of Nephrology, Department of Internal Medicine III, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
11. Ghrelin inhibits early osteogenic differentiation of C3H10T1/2 cells by suppressing Runx2 expression and enhancing PPAR gamma and C/EBPalpha expression
J Cell Biochem. 2009 Jan 21.
Kim SW, Choi OK, Jung JY, Yang JY,Cho SW,Shin CS, Park KS, Kim SY
Department of Internal Medicine, Seoul National University, College of Medicine, Seoul, South Korea.
12. Development of mesenchymal stem cells partially originate from the neural crest
Biochem Biophys Res Commun. 2009 Jan 20.
Morikawa S, Mabuchi Y, Niibe K, Suzuki S, Nagoshi N, Sunabori T, Shimmura S, Nagai Y, Nakagawa T, Okano H, Matsuzaki Y.
Department of Physiology, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan; Department of Dentistry and Oral Surgery, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan.
13. Application of a new chair-side method for the harvest of mesenchymal stem cells in a patient with nonunion of a fracture of the atrophic mandible – a case report
J Craniomaxillofac Surg. 2009 Jan 18.
Wongchuensoontorn C, Liebehenschel N, Schwarz U, Schmelzeisen R, Gutwald R, Ellis E 3rd, Sauerbier S.
Department of Oral and Maxillofacial Surgery, Srinakharinwirot University Bangkok, Thailand.
14. Human Amniotic Fluid Mesenchymal Stem Cells in Combination wth Hyperbaric Oxygen Augment Peripheral Nerve Regeneration
Neurochem Res. 2009 Jan 17.
Pan HC, Chin CS, Yang DY, Ho SP, Chen CJ, Hwang SM, Chang MH, Cheng FC.
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan.

15. Hyperthermia-treated msenchymal stem cells exert antitumor effects on human carcinoma cell line
Cancer. 2009 Jan 15;
Cho JA, Park H, Kim HK, Lim EH, Seo SW, Choi JS, Lee KW.
Adult Stem Cell Research Institute, Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.

16. Human mesenchymal stem cells inhibit cancer cell proliferation by secreting DKK-1
Leukemia. 2009 Jan 15.
Zhu Y, Sun Z, Han Q, Liao L, Wang J, Bian C, Li J, Yan X, Liu Y, Shao C, Zhao RC.
1Center for Tissue Engineering, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, Peoples Republic of China.
17. Early modulation of inflammation by mesenchymal stem cell after acute kidney injury
Int Immunopharmacol. 2009 Jan 13.
Semedo P, Palasio CG, Oliveira CD, Feitoza CQ, Gonçalves GM, Cenedeze MA, Wang PM, Teixeira VP, Reis MA, Pacheco-Silva A, Câmara NO.
Division of Nephrology, Federal University of São Paulo, São Paulo (UNIFESP), Brazil.

18. Comparative characterization of mesenchymal stem cells from eGFP transgenic and non-transgenic mice
BMC Cell Biol. 2009 Jan 13;
Ripoll CB, Bunnell BA.

19. The use of human mesenchymal stem cell-derived feeder cells for the cultivation of transplantable epithelial sheets.
Invest Ophthalmol Vis Sci. 2009 Jan 10.
Omoto M, Miyashita H, Shimmura S, Higa K, Kawakita T, Yoshida S, McGrogan M, Shimazaki J, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

20. In vitro dexamethasone pretreatment enhances bone formation of human mesenchymal stem cells in vivo
J Orthop Res. 2009 Jan 9.
Song IH, Caplan AI, Dennis JE.
Department of Orthopedics, Case Western Reserve University, Cleveland, Ohio.
21. Migration potential and gene expression profile of human mesenchymal stem cells induced by CCL25
Exp Cell Res. 2009 Jan 8.
Binger T, Stich S, Andreas K, Kaps C, Sezer O, Notter M, Sittinger M, Ringe J.
Tissue Engineering Laboratory and Berlin-Brandenburg Center for Regenerative Therapies, Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, CCM, Tucholskystr. 2, 10117 Berlin, Germany.
22. Stem cell sources to treat diabetes
J Cell Biochem. 2009 Jan 7
Furth ME, Atala A.
Department of Urology and Wake Forest, Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157.
23.Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopouetic stem cells in Fancg-/- mice in vivo.
Blood. 2009 Jan 7.
Li Y, Chen S, Yuan J, Yang Y, Li J, Ma J, Wu X, Freund M, Pollok K, Hanenberg H, Goebel WS, Yang FC. Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN, United States.
24. Synthesis of a Tissue-Engineered Periosteum with Acellular Dermal Matrix and Cultured Mesenchymal Stem Cells
Tissue Eng Part A. 2009 Jan 6.
Schönmeyr B, Clavin N, Avraham T, Longo V, Mehrara BJ.
Division of Plastic and Reconstructive Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York.
25. Telomerase Immortalized Human Amnion- and Adipose-Derived Mesenchymal Stem Cells: Maintenance of Differentiation and Immonomodulatori Charcteristics
Tissue Eng Part A. 2009 Jan 6.
Wolbank S, Stadler G, Peterbauer A, Gillich A, Karbiener M, Streubel B, Wieser M, Katinger H, van Griensven M, Redl H, Gabriel C, Grillari J, Grillari-Voglauer R.
1 Red Cross Blood Transfusion Service of Upper Austria , Linz, Austria ., 2 Austrian Cluster for Tissue Regeneration , Vienna/Linz, Austria ., 3 Ludwig Boltzmann Institute for Experimental and Clinical Traumatology/AUVA Research Center , Vienna/Linz, Austria ., 4 Bio-Products & Bio-Engineering AG , Vienna, Austria ., 5 Department of Biotechnology, Institute of Applied Microbiology, University of Natural Resources and Applied Life Sciences , Vienna, Austria ., 6 Department of Pathology, Medical University of Vienna , Vienna, Austria .
26. Pressure and Distortion Regulate Human Mesenchymal Stem Cell Gene Expression
Ann Biomed Eng. 2009 Jan 6.
Haudenschild AK, Hsieh AH, Kapila S, Lotz JC.
UCSF/UCB Joint Graduate Group in Bioengineering, San Francisco, CA, USA.
27. Umbilical cord mesenchymal stem cells: role of regulatory genes in their differentiation to osteoblasts
Ciavarella S, Dammacco F, De Matteo M, Loverro G, Silvestris F.
Stem Cells Dev. 2009 Jan 6.
University of Bari Medical School, Department of Internal Medicine and Clinical Oncology, Bari, Bari, Italy;
28. Human adipose-derived mesenchymal stem cells reduce inflammatory and T-cell responses and induce regulatoru T cells in vitro in rheumatoid arthritis
Ann Rheum Dis. 2009 Jan 5
Gonzalez-Rey E, Gonzalez MA, Varela N, O'Valle F, Hernandez-Cortes P, Rico L, Büscher D, Delgado M.
School of Medicine, Seville University, Seville, Spain.
29. Why are MSCs therapeutic? New data: new insight
J Pathol. 2009 Jan;
Caplan AI.
Skeletal Research Center, Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
30. Development of sarcomas in mice implanted with mesenchymal stem cells seeded onto bioscaffolds
Carcinogenesis. 2009 Jan; Epub 2008 Oct 9.
Tasso R, Augello A, Carida' M, Postiglione F, Tibiletti MG, Bernasconi B, Astigiano S, Fais F, Truini M, Cancedda R, Pennesi G.
Department of Oncology, Biology and Genetics, University of Genova.
31. Fetal mesenchymal stem cells:isolation, properties and potential use in perinatology and regenerative medicine.
BJOG. 2009 Jan;
Gucciardo L, Lories R, Ochsenbein-Kölble N, Done' E, Zwijsen A, Deprest J.
Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, Leuven, Belgium.
32. Multi- and inter- disciplinary science in personalized delivery of stem cells for tissue repair
Curr Stem Cell Res Ther. 2009 Jan;
Heinrich AC, Patel SA, Reddy BY, Milton R, Rameshwar P.
UMDNJ-New Jersey Medical School, 185 South Orange Ave., Newark, NJ 07103, USA.
33. Comparative proteomic analysis of human mesenchymal and embryonic stem cells: towards the definition of a mesenchymal stem cell proteomic signature
Proteomics. 2009 Jan;
Roche S, Delorme B, Oostendorp RA, Barbet R, Caton D, Noel D, Boumediene K, Papadaki HA, Cousin B, Crozet C, Milhavet O, Casteilla L, Hatzfeld J, Jorgensen C, Charbord P, Lehmann S.
CNRS, Institut de Génétique Humaine, UPR1142, Montpellier, France.
34. Contribution of stem cells to kidney repair
Curr Stem Cell Res Ther. 2009 Jan;4(1):2-8.
Bussolati B, Hauser PV, Carvalhosa R, Camussi G.
Cattedra di Nefrologia, Dipartimento di Medicina Interna, Ospedale Maggiore S. Giovanni Battista, Corso Dogliotti 14, Turin, Italy.
35. Production of hepatocyte-like cells from human amnion
Methods Mol Biol. 2009;
Miki T, Marongiu F, Ellis EC, Dorko K, Mitamura K, Ranade A, Gramignoli R, Davila J, Strom SC.
Departments of Pathology and Surgery and McGowan Institute for Regenerative Medicine, University of Pittsburgh, USA.
36. Tissue-engineered skin containing mesenchymal stem cellsimproves burn wounds.
Artif Organs. 2008 Dec;
Liu P, Deng Z, Han S, Liu T, Wen N, Lu W, Geng X, Huang S, Jin Y. Department of Oral Histology and Pathology, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi, China.
37. Comparison of human placenta- and bone marrow-derived multipotent mesenchymal stem cells.
Stem Cells Dev. 2008 Dec;
Barlow S, Brooke G, Chatterjee K, Price G, Pelekanos R, Rossetti T, Doody M, Venter D, Pain S, Gilshenan K, Atkinson K.
Adult Stem Cell Laboratory, Biotherapy Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.
38. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice.
Cell Mol Immunol. 2008 Dec;
Zhou K, Zhang H, Jin O, Feng X, Yao G, Hou Y, Sun L.
Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Jiangsu, China.
39. Neuronal characteristics of amniotic fluid derived cells after adenoviral transformation
Cell Biol Int. 2008 Dec; Epub 2008 Sep 25.
Arnhold S, Post C, Glüer S, Hoopmann M, Wenisch S, Volpers C, Addicks K.
Department of Veterinary Anatomy, Histology and Embryology, Justus-Liebig, University of Giessen, Frankfurter Street 98, 35392 Giessen, Germany.
40. Non-invasive longitudinal tracking of human amniotic fluid stem cells in the mouse heart.
Stem Cells Dev. 2008 Dec;
Delo DM, Olson J, Baptista PM, D'Agostino RB Jr, Atala A, Zhu JM, Soker S.
Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157, USA.
41. Preliminary studies on repairing osteochondral defects in the rabbit knee joint by using porous PA66/n-HA combination mesenchymal stem cells
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2008 Dec;
Wu J, Yang T, Liu Y, Guo T, Mu Y, Li Y.
Department of Orthopaedics, West China Hospital of Sichuan University, Chengdu 610041, China.
42. Mesenchymal stem cells from human umbilical cords ameliorate mouse hepatic injury in vivo.
Liver Int. 2008 Dec 29.
Yan Y, Xu W, Qian H, Si Y, Zhu W, Cao H, Zhou H, Mao F.
School of Medical Technology, Jiangsu University, Jiangsu, China.
43. The free fatty acid metabolome in cerebral ischemia following human mesenchymal stem cell transplantation in rats.
Clin Chim Acta. 2008 Dec 25.
Paik MJ, Li WY, Ahn YH, Lee PH, Choi S, Kim KR, Kim YM, Bang OY, Lee G.
Institute for Neuroregeneration and Stem Cell Research, Ajou University School of Medicine, Suwon, South Korea.
44. Ability of polyurethane foams to support cell proliferation and the differentiation of MSCs into osteoblasts.
Acta Biomater. 2008 Dec 24.
Zanetta M, Quirici N, Demarosi F, Tanzi MC, Rimondini L, Farè S.
Department of Bioengineering, Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133 Milan, Italy.
45. Mesenchymal stem cells: the fibroblasts' new clothes?
Haematologica. 2008 Dec 23.
Haniffa MA, Collin MP, Buckley CD, Dazzi F.
Hematological Sciences.
46. Stem Cell Therapy for the Kidney?
Am J Ther. 2008 Dec 15.
Zubko R, Frishman W.
1Department of Medicine, Oregon Health Sciences University, Portland, OR; and 2Department of Medicine, New York Medical College-Westchester Medical Center, Valhalla, NY.
47. Baculovirus-transduced mouse amniotic fluid-derived stem cells maintain differentiation potential.
Ann Hematol. 2008 Dec 6.
Liu ZS, Xu YF, Feng SW, Li Y, Yao XL, Lu XL, Zhang C.
Department of Neurology, First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road 2, Guangzhou, 510080, People's Republic of China.
48. Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials.
Br J Haematol. 2008 Dec 5.
Brooke G, Rossetti T, Pelekanos R, Ilic N, Murray P, Hancock S, Antonenas V, Huang G, Gottlieb D, Bradstock K, Atkinson K.
Adult Stem Cell Laboratory, Biotherapy Program, Mater Medical Research Institute, Brisbane, Queesland, Australia.
49. Human amniotic fluid stem cells can integrate and differentiate into epithelial lung lineages.
Stem Cells. 2008 Nov; Epub 2008 Aug 21.
Carraro G, Perin L, Sedrakyan S, Giuliani S, Tiozzo C, Lee J, Turcatel G, De Langhe SP, Driscoll B, Bellusci S, Minoo P, Atala A, De Filippo RE, Warburton D.
Developmental Biology, Regenerative Medicine and Surgery Program, Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine and School of Dentistry, Los Angeles, California 90027, USA.
50. Stem cells in urology.
Nat Clin Pract Urol. 2008 Nov; Epub 2008 Oct 14.
Aboushwareb T, Atala A.
Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
51. Characterization and hepatogenic differentiation of mesenchymal stem cells from human amniotic fluid and human bone marrow: a comparative study.
Cell Biol Int. 2008 Nov; Epub 2008 Aug 20
Zheng YB, Gao ZL, Xie C, Zhu HP, Peng L, Chen JH, Chong YT.
Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, PR China.
52. Human amniotic fluid stem cells can integrate and differentiate into epithelial lung lineages.
Stem Cells. 2008 Nov; Epub 2008 Aug 21.
Carraro G, Perin L, Sedrakyan S, Giuliani S, Tiozzo C, Lee J, Turcatel G, De Langhe SP, Driscoll B, Bellusci S, Minoo P, Atala A, De Filippo RE, Warburton D.
Developmental Biology, Regenerative Medicine and Surgery Program, Saban Research Institute, Children's Hospital Los Angeles, Keck School of Medicine and School of Dentistry, Los Angeles, California 90027, USA.
53. Isolation of human mesenchymal stem cells from third-trimester amniotic fluid.
Int J Gynaecol Obstet. 2008 Nov; Epub 2008 Aug 29.
You Q, Cai L, Zheng J, Tong X, Zhang D, Zhang Y.
Stem Cell Investigation Center, Department of Gynecology and Obstetrics, Harbin Medical University, Heilongjiang, China.
54. Potential of mesenchymal stem cells as immune therapy in solid-organ transplantation.
Transpl Int. 2008 Nov 1.
Crop M, Baan C, Weimar W, Hoogduijn M.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
55. High transduction efficiency of human amniotic fluid stem cells mediated by adenovirus vectors.
Stem Cells Dev. 2008 Oct;
Grisafi D, Piccoli M, Pozzobon M, Ditadi A, Zaramella P, Chiandetti L, Zanon GF, Atala A, Zacchello F, Scarpa M, De Coppi P, Tomanin R.
Gene Therapy Laboratory and Centre for Rare Diseases, Department of Pediatrics, University of Padova, Padova, Italy.
56. Deleted in Azoospermia-Like (DAZL) gene-expressing cells in human amniotic fluid: a new source for germ cells research?
Fertil Steril. 2008 Sep; Epub 2007 Nov 26.
Stefanidis K, Loutradis D, Koumbi L, Anastasiadou V, Dinopoulou V, Kiapekou E, Lavdas AA, Mesogitis S, Antsaklis A.
Laboratory of Stem Cells, Division of Reproductive Medicine, 1st Department of Obstetrics and Gynecology, Alexandra Maternity Hospital, University of Athens Medical School, Athens, Greece.
57. Differentiation of human amniotic fluid stem cells into cardiomyocytes through embryonic body formation
Sheng Wu Gong Cheng Xue Bao. 2008 Sep;
Wang H, Chen S, Cheng X, Dou Z, Wang H.
Northwest A & F University, College of Veterinary Medicine, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Shaanxi Stem Cell Engineering and Technology Research Center, Yangling 712100, China.
58. Human amniotic fluid stem cells: a new perspective.
Amino Acids. 2008 Aug; Epub 2007 Aug 21
Siegel N, Rosner M, Hanneder M, Freilinger A, Hengstschläger M.
Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Vienna, Austria.
59. Stem/progenitor cells in lung development, injury repair, and regeneration.
Proc Am Thorac Soc. 2008 Aug 15;
Warburton D, Perin L, Defilippo R, Bellusci S, Shi W, Driscoll B.
Developmental Biology, Regenerative Medicine and Surgery Program, Saban Research Institute, Children's Hospital Los Angeles, 4661 Sunset Boulevard, Los Angeles CA 90027, USA.
60. Combination of G-CSF Administration and Human Amniotic Fluid Mesenchymal Stem Cell Transplantation Promotes Peripheral Nerve Regeneration.
Neurochem Res. 2008 Aug 9.
Pan HC, Chen CJ, Cheng FC, Ho SP, Liu MJ, Hwang SM, Chang MH, Wang YC.
Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan,
61. Potential role of culture mediums for successful isolation and neuronal differentiation of amniotic fluid stem cells.
Int J Immunopathol Pharmacol. 2008 Jul-Sep;
Orciani M, Emanuelli M, Martino C, Pugnaloni A, Tranquilli AL, Di Primio R.
Department of Molecular Pathology and Innovative Therapies, Histology Section, Marche Polytechnic University, Ancona, Italy.

62. Adult stem cells and their trans-differentiation potential-perspectives and therapeutic applications.
J Mol Med. 2008 Jul 16.
Hombach-Klonisch S, Panigrahi S, Rashedi I, Seifert A, Alberti E, Pocar P, Kurpisz M, Schulze-Osthoff K, Mackiewicz A, Los M.
Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Canada.
63. Cryopreserved amniotic fluid-derived cells: a lifelong autologous fetal stem cell source for heart valve tissue engineering.
J Heart Valve Dis. 2008 Jul;
Schmidt D, Achermann J, Odermatt B, Genoni M, Zund G, Hoerstrup SP.
Clinic for Cardiovascular Surgery, Department of Surgical Research, University, University Hospital, Zurich, Switzerland.

64. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes.
Diabetes. 2008 Jul;
Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH.
Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

65. Application of stem cells in bone repair.

Skeletal Radiol. 2008 Jul; Kandel, Rita R
Waese EY, Kandel RA, Stanford WL.
Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, Canada M5S 3G9.
66. Updates on stem cells and their applications in regenerative medicine.
J Tissue Eng Regen Med. 2008 Jun;
Bajada S, Mazakova I, Richardson JB, Ashammakhi N.
Institute for Science and Technology in Medicine, Keele University, Staffordshire, UK.

67. Placental mesenchymal and cord blood stem cell therapy for dilated cardiomyopathy.
Reprod Biomed Online. 2008 Jun;
Ichim TE, Solano F, Brenes R, Glenn E, Chang J, Chan K, Riordan NH.
Medistem Laboratories Inc., 2027 E Cedar Street Suite 102 Tempe, AZ 85281, USA.
68. Preclinical regulatory validation of a 3-stage amniotic mesenchymal stem cell manufacturing protocol.
J Pediatr Surg. 2008 Jun;
Steigman SA, Armant M, Bayer-Zwirello L, Kao GS, Silberstein L, Ritz J, Fauza DO.
Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.

69. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells.
Pain Physician. 2008 May-Jun;
Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D.
Regenerative Sciences Inc (RSI), Centeno-Schultz Clinic, Westminster, CO 80020, USA

70. Oxytocin receptor- and Oct-4-expressing cells in human amniotic fluid.

Gynecol Endocrinol. 2008 May;
Stefanidis K, Loutradis D, Anastasiadou V, Bletsa R, Kiapekou E, Drakakis P, Beretsos P, Elenis E, Mesogitis S, Antsaklis A.
Laboratory of Stem Cells, Division of Reproductive Medicine, Alexandra Maternity Hospital, Athens, Greece.

71. Regenerative medicine for heart failure
Nippon Rinsho. 2008 May;
Nagaya N, Kitamura S.
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute.

72. Human amniotic epithelial cells ameliorate behavioral dysfunction and reduce infarct size in the rat middle cerebral artery occlusion model.
Shock. 2008 May;
Liu T, Wu J, Huang Q, Hou Y, Jiang Z, Zang S, Guo L.
Genetic Engineering Group, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
73. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study.
Lancet. 2008 May 10;
Comment in:
Lancet. 2008 May 10;
Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O; Developmental Committee of the European Group for Blood and Marrow Transplantation.
Haematology Centre and Centre of Allogeneic Stem Cell Transplantation, Division of Clinical Immunology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
74. Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy.
Clin Pharmacol Ther. 2008 May; Epub 2007 Sep 26.
Comment in:
Clin Pharmacol Ther. 2008 May;
Lee PH, Kim JW, Bang OY, Ahn YH, Joo IS, Huh K.
Department of Neurology, Ajou University College of Medicine, Suwon, South Korea.

75. Liver stem cells: a scientific and clinical perspective.
J Gastroenterol Hepatol. 2008 May;
Dan YY, Yeoh GC.
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Hospital, Singapore.
76. Stem cell and regenerative science applications in the development of bioengineering of renal tissue.
Pediatr Res. 2008 May;
Perin L, Giuliani S, Sedrakyan S, DA Sacco S, De Filippo RE.
Children's Hospital Los Angeles, Division of Urology, Saban Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.
77. Sources of stem cells for regenerative medicine.
Stem Cell Rev. 2008 Spring;
Hipp J, Atala A. Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157, USA.

78. Dental pulp stem cells: a promising tool for bone regeneration.
Stem Cell Rev. 2008 Spring;
D'Aquino R, Papaccio G, Laino G, Graziano A.
Dipartimento di Discipline Odontostomatologiche, Ortodontiche e Chirurgiche, Secondo Ateneo di Napoli (Italy), Naples, Italy.
79. Heart regeneration: what cells to use and how?
Curr Opin Pharmacol. 2008 Apr;8(2):211-8. Epub 2008 Mar 4.
Tousoulis D, Briasoulis A, Antoniades C, Stefanadi E, Stefanadis C.
A' Cardiology Department, Athens University Medical School, Athens, Greece. drtousoulis@hotmail.com

80. Biologic characteristics of mesenchymal stromal cells and their clinical applications in pediatric patients.
J Pediatr Hematol Oncol. 2008 Apr;
Pelagiadis I, Dimitriou H, Kalmanti M.
Department of Pediatric Hematology-Oncology, University Hospital of Heraklion, University of Crete Medical School, Heraklion, Crete, Greece.

81. Multipotent mesenchymal stromal cells from amniotic fluid: solid perspectives for clinical application.

Haematologica. 2008 Mar; Epub 2008 Feb 11.
Sessarego N, Parodi A, Podestà M, Benvenuto F, Mogni M, Raviolo V, Lituania M, Kunkl A, Ferlazzo G, Bricarelli FD, Uccelli A, Frassoni F.
Centro Cellule Staminali e Terapia Cellulare, Ospedale San Martino, L.go R. Benzi 10, 16132 Genova Italy.
82. Different cardiovascular potential of adult- and fetal-type mesenchymal stem cells in a rat model of heart cryoinjury.
Cell Transplant. 2008;
Iop L, Chiavegato A, Callegari A, Bollini S, Piccoli M, Pozzobon M, Rossi CA, Calamelli S, Chiavegato D, Gerosa G, De Coppi P, Sartore S.
Department of Biomedical Sciences, University of Padua School of Medicine, Padua, Italy.
83. Characterization of human amniotic fluid stem cells and their pluripotential capability
Methods Cell Biol. 2008;
Perin L, Sedrakyan S, Da Sacco S, De Filippo R.
Childrens Hospital Los Angeles, Saban Research Institute, Developmental Biology Program, Keck School of Medicine, University of Southern California, USA.
84. Comparative characterization of cultured human term amnion epithelial and mesenchymal stromal cells for application in cell therapy
Cell Transplant. 2008
Bilic G, Zeisberger SM, Mallik AS, Zimmermann R, Zisch AH. Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland.
85. Adult mesenchymal stromal stem cells for therapeutic applications.
Minim Invasive Ther Allied Technol. 2008;
Spitkovsky D, Hescheler J.
Institute of Neurophysiology, University of Cologne, Cologne, Germany.
86. Therapeutic applications of mesenchymal stromal cells.
Semin Cell Dev Biol. 2007 Dec; Epub 2007 Sep 18.
Brooke G, Cook M, Blair C, Han R, Heazlewood C, Jones B, Kambouris M, Kollar K, McTaggart S, Pelekanos R, Rice A, Rossetti T, Atkinson K. Adult Stem Cell Laboratory, Biotherapy Program, Mater Medical Research Institute, Brisbane, Queensland, Australia.
87. Stem cells in amniotic fluid as new tools to study human genetic diseases.
Stem Cell Rev. 2007 Dec;
Siegel N, Rosner M, Hanneder M, Valli A, Hengstschläger M.
Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria
88. Molecular and proteomic characterization of human mesenchymal stem cells derived from amniotic fluid: comparison to bone marrow mesenchymal stem cells.
Stem Cells Dev. 2007 Dec;
Roubelakis MG, Pappa KI, Bitsika V, Zagoura D, Vlahou A, Papadaki HA, Antsaklis A, Anagnou NP. Cell and Gene Therapy Laboratory, Centre of Basic Research II, Biomedical Research Foundation of the Academy of Athens (BRF), Athens, Greece.

89. Renal differentiation of amniotic fluid stem cells.
Cell Prolif. 2007 Dec;
Perin L, Giuliani S, Jin D, Sedrakyan S, Carraro G, Habibian R, Warburton D, Atala A, De Filippo RE.
Childrens Hospital Los Angeles, Saban Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90027, USA.
90. Chondrogenic differentiation of amniotic fluid-derived stem cells.
J Mol Histol. 2007 Oct; Epub 2007 Aug 1.
Kolambkar YM, Peister A, Soker S, Atala A, Guldberg RE.
Wallace H Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
91. Isolation and differentiation of human mesenchymal stem cells obtained from second trimester amniotic fluid; experiments at Chang Gung Memorial Hospital.
Chang Gung Med J. 2007 Sep-Oct;
Peng HH, Wang TH, Chao AS, Chang SD.
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, Chang Gung University College of Medicine, Taoyuan, Taiwan.

92. Biochemical heterogeneity of mesenchymal stem cell populations: clues to their therapeutic efficacy.
Cell Cycle. 2007 Sep; Epub 2007 Sep 24.
Phinney DG. Center for Gene Therapy, Tulane University Health Sciences Center, New Orleans, Louisiana, USA.
93. Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeuticapplications in regenerative medicine and cancer therapies.
Clin Pharmacol Ther. 2007 Sep;Epub 2007 Aug 1.
Mimeault M, Hauke R, Batra SK.
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA.

94. Mesenchymal cells from human amniotic fluid survive and migrate after transplantation into adult rat brain.
Cell Biol Int. 2007 Aug; Epub 2007 Feb 9.
Cipriani S, Bonini D, Marchina E, Balgkouranidou I, Caimi L, Grassi Zucconi G, Barlati S.Department of Cellular and Environmental Biology, University of Perugia, Via Elce di sotto, 06123 Perugia, Italy.

95. Tissue engineering from human mesenchymal amniocytes: a prelude to clinical trials.
J Pediatr Surg. 2007 Jun;
Kunisaki SM, Armant M, Kao GS, Stevenson K, Kim H, Fauza DO.
Department of Surgery, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.

96. Engineering tissues, organs and cells.
J Tissue Eng Regen Med. 2007 Mar-Apr;
Atala A. Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
97. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study.
Iran J Immunol. 2007 Mar;
Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, Alimoghaddom K, Talebian F, Hooshmand F, Ghavamzadeh A, Nikbin B.
Hematology-Oncology & BMT Research Center, Tehran, Iran.

98. Human amniotic fluid-derived stem cells have characteristics of multipotent stem cells.
Cell Prolif. 2007 Feb;
Kim J, Lee Y, Kim H, Hwang KJ, Kwon HC, Kim SK, Cho DJ, Kang SG, You J.
Department of Biotechnology, College of Natural Science, Seoul Women's University, Nowon-Gu, Seoul, Korea.
99. Isolation of amniotic stem cell lines with potential for therapy.
Nat Biotechnol. 2007 Jan; Epub 2007 Jan 7.
Comment in:
Nat Biotechnol. 2007 Jan;
Nat Biotechnol. 2007 Nov;
Nat Biotechnol. 2008 Mar;
De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A.Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1094, USA.

100. Mesenchymal stem cells: a new versatile therapeutic option
Rev Med Liege. 2007;
Baron F, Gothot A.
Service d'Hématologie clinique, CHU Sart Tilman, Liège, Belgique.

101. A real-time PCR approach to evaluate adipogenic potential of amniotic fluid-derived human mesenchymal stem cells.
Stem Cells Dev. 2006 Oct;
De Gemmis P, Lapucci C, Bertelli M, Tognetto A, Fanin E, Vettor R, Pagano C, Pandolfo M, Fabbri A.
BIRD Europe Institute, Vicenza, Italy.

102. The role of stem cells in physiology, pathophysiology, and therapy of the liver.
Stem Cell Rev. 2006;
Sharma AD, Cantz T, Manns MP, Ott M.Department of Gastroenterology, Hepatology, Endocrinology, Center of Internal Medicine, Hannover Medical School, Hannover, Germany.

103. Amniotic fluid and placental stem cells.
Methods Enzymol. 2006;
Delo DM, De Coppi P, Bartsch G Jr, Atala A.
Wake Forest University School of Medicine, Wake Forest Institute for Regenerative Medicine, Winston-Salem, NC, USA.










1. Histol Histopathol. 2009 Mar;
Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy.
Mobasheri A, Csaki C, Clutterbuck AL, Rahmanzadeh M, Shakibaei M.
Division of Veterinary Medicine, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, Loughborough, United Kingdom. ali.mobasheri@nottingham.ac.uk
Defects of load-bearing connective tissues such as articular cartilage, often result from trauma, degenerative or age-related disease. Osteoarthritis (OA) presents a major clinical challenge to clinicians due to the limited inherent repair capacity of articular cartilage. Articular cartilage defects are increasingly common among the elderly population causing pain, reduced joint function and significant disability among affected patients. The poor capacity for self-repair of chondral defects has resulted in the development of a large variety of treatment approaches including Autologous Chondrocyte Transplantation (ACT), microfracture and mosaicplasty methods. In ACT, a cartilage biopsy is taken from the patient and articular chondrocytes are isolated. The cells are then expanded after several passages in vitro and used to fill the cartilage defect. Since its introduction, ACT has become a widely applied surgical method with good to excellent clinical outcomes. More recently, classical ACT has been combined with tissue engineering and implantable scaffolds for improved results. However, there are still major problems associated with the ACT technique which relate mainly to chondrocyte de-differentiation during the expansion phase in monolayer culture and the poor integration of the implants into the surrounding cartilage tissue. Novel approaches using mesenchymal stem cells (MSCs) as an alternative cell source to patient derived chondrocytes are currently on trial. MSCs have shown significant potential for chondrogenesis in animal models. This review article discusses the potential of MSCs in tissue engineering and regenerative medicine and highlights their potential for cartilage repair and cell-based therapies for osteoarthritis and a range of related osteoarticular disorders.




2. J Oral Maxillofac Surg. 2009 Feb;
Effect of mesenchymal stem cells and platelet-rich plasma on the healing of standardized bone defects in the alveolar ridge: a comparative histomorphometric study in minipigs.
Pieri F, Lucarelli E, Corinaldesi G, Fini M, Aldini NN, Giardino R, Donati D, Marchetti C.
Department of Odontostomatological Sciences, University of Bologna, Bologna, Italy. checcopieri@yahoo.it
PURPOSE: The purpose of this study was to test the effect of the combination of mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) incorporated into a fluorohydroxyapatite (FHA) scaffold on bone regeneration in cylindrical defects in the edentulous mandibular ridge of minipigs. MATERIALS AND METHODS: Two mandibular premolar teeth were extracted bilaterally in 8 adult minipigs. After 2 months, 4 standardized defects of 3.5 mm diameter and 8 mm depth were created in each root site. The defects were randomly grafted with autogenous mandibular bone, FHA alone, PRP-FHA, or MSCs-PRP-FHA. A resorbable collagen membrane was placed over the defect area and the flaps were sutured. The animals were sacrificed 3 months later and biopsy samples were taken from the defect sites for histologic and histomorphometric assessment. RESULTS: There was no evidence of inflammation or adverse tissue reaction with either treatment. MSCs-PRP-FHA-treated sites showed new vital bone between residual grafting particles. PRP-FHA- and FHA-treated sites showed residual particles in a background of marrow soft tissue with a moderate quantity of newly formed bone. Autogenous bone (46.97%) and MSCs-PRP-FHA (45.28%) produced a significantly higher amount of vital bone than PRP-FHA (37.95%), or FHA alone (36.03%). Further, the MSCs-PRP-FHA-treated defects showed a significantly higher percentage of contact between graft particles and newly formed bone compared with PRP-FHA and FHA group (59.23% vs 48.37% and 46.43%, respectively). CONCLUSIONS: Our results suggest that, in this animal model, the addition of MSCs to PRP-FHA enhances bone formation after 3 months.





3. Eur J Heart Fail. 2009 Feb
Transplantation of mesenchymal stem cells within a poly(lactide-co-{varepsilon}-caprolactone) scaffold improves cardiac function in a rat myocardial infarction model.
Jin J, Jeong SI, Shin YM, Lim KS, Shin HS, Lee YM, Koh HC, Kim KS.
Division of Cardiology, College of Medicine, Hanyang University, 17 Haengdang-dong, Seongdong-ku, Seoul 133-791, South Korea.
AIMS: Cardiac tissue engineering has been proposed as an appropriate method to repair myocardial infarction (MI). Evidence suggests that a cell with scaffold combination was more effective than a cell-only implant. Nevertheless, to date, there has been no research into elastic biodegradable poly(lactide-co-epsilon-caprolactone) (PLCL) scaffolds. The aim of this study was to investigate the effect of mesenchymal stem cells (MSCs) with elastic biodegradable PLCL scaffold transplants in a rat MI model. METHODS AND RESULTS: Ten days after inducing MI through the cryoinjury method, a saline control, MSC, PLCL scaffold, or MSC-seeded PLCL scaffold was transplanted onto the hearts. Four weeks after transplantation, cardiac function and histology were evaluated. Transplanted MSCs survived and differentiated into cardiomyocytes in the injured region. Left ventricular ejection fraction in the MSC + PLCL group increased by 23% compared with that in the saline group; it was also higher in the MSC group. The infarct area in the MSC + PLCL group was decreased by 29% compared with that in the saline group; it was also reduced in the MSC group. CONCLUSION: Mesenchymal stem cells plus PLCL should be an excellent combination for cardiac tissue engineering.


4. Transplantation. 2009 Jan 27;
Mesenchymal stem cells remain host-derived independent of the source of the stem-cell graft and conditioning regimen used.
Bartsch K, Al-Ali H, Reinhardt A, Franke C, Hudecek M, Kamprad M, Tschiedel S, Cross M, Niederwieser D, Gentilini C.
Department of Hematology and Oncology, University of Leipzig, Leipzig, Germany. Kristina.Bartsch@medizin.uni-leipzig.de
BACKGROUND: Human bone marrow contains hematopoietic stem cells and stroma cells known as mesenchymal stem cells (MSC). MSC are cells with the morphological features of fibroblasts, which, in addition to their nursing function for hematopoietic stem cells, retain the ability to differentiate into cartilage, bone, fat, muscle, and tendon and have an important immunmodulatory function. To understand in more detail hematopoietic engraftment and immune modulation after hematopoietic cell transplantation, we investigated the ability of donor MSC to engraft after hematopoietic cell transplantation in dependency to the conditioning regimen (myeloablative vs. reduced intensity) and source of the graft (bone marrow vs. peripheral blood). METHODS: Bone marrow MSC of 12 patients were analyzed, a median of 23.4 (range 0.9-137.8) months after human leukocyte antigen matched but gender mismatched bone marrow transplantation after myeloablative conditioning (n=4) or peripheral blood cell transplantation after myeloablative (n=4) or reduced intensity conditioning (n=4). MSC were characterized by morphology, positivity for CD 105+, CD73+, CD 44+, and CD 90+, and by their capacity to differentiate into adipocytic and osteogenic cells. Recipient and donor origins were determined by fluorescent in situ hybridization for sex chromosomes. RESULTS: While overall blood and bone marrow chimerism was 100% donor type, MSC remained in all patients of recipient origin (>96%). There was no difference between patients receiving bone marrow and peripheral blood grafts, nor was any difference observed between patients receiving full intensity in comparison with reduced intensity conditioning. CONCLUSIONS: We conclude that MSC remain of host type irrespective of the conditioning regimen and graft source.








5. J Biomed Mater Res A. 2009 Jan 23.
Evaluation of the osteogenic potential and vascularization of 3D poly(3)hydroxybutyrate scaffolds subcutaneously implanted in nude rats.
Rentsch C, Rentsch B, Breier A, Hofmann A, Manthey S, Scharnweber D, Biewener A, Zwipp H.
Department of Trauma and Reconstructive Surgery, University Hospital Carl Gustav Carus Dresden, Fetscher Strasse 74, 01307 Dresden, Germany.
The aim of this study was to evaluate the osteogenic potential and the vascularization of embroidered, tissue engineered, and cell-seeded 3D poly(3)hydroxybutyrate (PHB) scaffolds in nude rats. Collagen I (coll I)- and collagen I/chondroitin sulfate (coll I/CS)-coated PHB scaffolds were seeded with human mesenchymal stem cells (hMSCs). Proliferation and differentiation were characterized by different biochemical assays in vitro. For animal experiments, the cells were cultivated on coll I- or coll I/CS-coated scaffolds and either expanded or osteogenically differentiated. Scaffolds were piled up to create a 3D scaffold pad and implanted subcutaneously into nude rats. In vitro hMSC showed proliferation and differentiation on PHB scaffolds. Alkaline phosphatase (ALP) and calcium increased in the differentiation medium and in the presence of coll I/CS. In vivo blood vessels were found in the scaffold-stack. Histological/immunohistological analyses of explanted scaffolds showed osteogenic markers such as osteopontin, osteonectin, and coll I around the PHB fibers. Coll I/CS-coated scaffolds with expanded hMSC showed higher values of ALP and calcium than the other combinations. Embroidered PHB scaffolds, coated with extracellular matrix components, provided an adequate environment and, therefore, a template for hMSC which could be differentiated in osteogenic direction. (c) 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2009.






6. J Tissue Eng Regen Med. 2009 Jan 23.
Mesenchymal progenitor cells derived from traumatized human muscle.
Jackson WM, Aragon AB, Djouad F, Song Y, Koehler SM, Nesti LJ, Tuan RS.
Cartilage Biology and Orthopaedic Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA.
Mesenchymal stem cells (MSCs) derived from adult tissues are an important candidate cell type for cell-based tissue engineering and regenerative medicine. Currently, clinical applications for MSCs require additional surgical procedures to harvest the autologous MSCs (i.e. from bone marrow) or commercial allogeneic alternatives. We have recently identified a population of mesenchymal progenitor cells (MPCs) in traumatized muscle tissue that has been surgically debrided from traumatic orthopaedic extremity wounds. The purpose of this study was to evaluate whether MPCs derived from traumatized muscle may provide a clinical alternative to bone-marrow MSCs, by comparing their morphology, proliferation capacity, cell surface epitope profile and differentiation capacity. After digesting the muscle tissue with collagenase, the MPCs were enriched by a direct plating technique. The morphology and proliferation rate of the muscle-derived MPCs was similar to bone-marrow derived MSCs. Both populations expressed cell surface markers characteristic for MSCs (CD 73, CD 90 and CD105), and did not express markers typically absent on MSCs (CD14, CD34 and CD45). After 21 days in specific differentiation media, the histological staining and gene expression of the MPCs and MSCs was characteristic for differentiation into osteoblasts, chondrocytes and adipocytes, but not into myoblasts. Our findings demonstrate that traumatized muscle-derived MPCs exhibit a similar phenotype and resemble MSCs derived from the bone marrow. MPCs harvested from traumatized muscle tissue may be considered for applications in tissue engineering and regenerative medicine following orthopaedic trauma requiring circumferential debridement. Copyright (c) 2009 John Wiley & Sons, Ltd.








7. J Cell Physiol. 2009 Jan 23.
Perfusion affects the tissue developmental patterns of human mesenchymal stem cells in 3D scaffolds.
Zhao F, Grayson WL, Ma T, Irsigler A.
Department of Chemical and Biomedical Engineering, Florida State University, Tallahassee, Florida.
Human mesenchymal stem cells (hMSCs) developed in three-dimensional (3D) scaffolds are significantly affected by culture conditions. We hypothesized that the hydrodynamic forces generated in perfusion bioreactors significantly affected hMSC functionality in 3D scaffolds by shaping the extracellular matrix (ECM) proteins. In this study, hMSCs were grown in 3D poly(ethylene terephthalate) (PET) scaffolds in static and a parallel perfusion system under similar initial conditions for up to 35 days. Results demonstrated that even at very low media velocities (O [10(-4) cm/sec]), perfusion cultures affected the ability of hMSCs to form an organized ECM network as illustrated by the immunostaining of collagen I and laminin fibrous structure. The change in the ECM microenvironment consequently influenced the nuclear shape. The hMSCs grown at the lower surface of static culture displayed a 15.2 times higher nuclear elongation than those at the upper surface, whereas cells grown in the perfusion bioreactor displayed uniform spherical nuclei on both surfaces. The difference in ECM organization and nuclear morphology associated with gene expression and differentiation characteristics of hMSCs. The cells exhibited lower CFU-F colony forming ability and decreased expressions of stem-cell genes of Rex-1 and Oct-4, implying a less primitive stem-cell phenotype was maintained in the perfusion culture relative to the static culture conditions. The significantly higher expression level of osteonectin gene in the perfusion culture at day 28 indicated an upregulation of osteogenic ability of hMSCs. The study highlights the critical role of dynamic culture conditions on 3D hMSC construct development and properties. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.





8. J Cell Physiol. 2009 Jan 23.
Secretome from mesenchymal stem cells induces angiogenesis via Cyr61.
Estrada R, Li N, Sarojini H, An J, Lee MJ, Wang E.
Gheens Center on Aging, University of Louisville School of Medicine, Louisville, Kentucky.
It is well known that bone marrow-derived mesenchymal stem cells (MSCs) are involved in wound healing and regeneration responses. In this study, we globally profiled the proteome of MSCs to investigate critical factor(s) that may promote wound healing. Cysteine-rich protein 61 (Cyr61) was found to be abundantly present in MSCs. The presence of Cyr61 was confirmed by immunofluorescence staining and immunoblot analysis. Moreover, we showed that Cyr61 is present in the culture medium (secretome) of MSCs. The secretome of MSCs stimulates angiogenic response in vitro, and neovascularization in vivo. Depletion of Cyr61 completely abrogates the angiogenic-inducing capability of the MSC secretome. Importantly, addition of recombinant Cyr61 polypeptides restores the angiogenic activity of Cyr61-depleted secretome. Collectively, these data demonstrate that Cyr61 polypeptide in MSC secretome contributes to the angiogenesis-promoting activity, a key event needed for regeneration and repair of injured tissues. J. Cell. Physiol. (c) 2009 Wiley-Liss, Inc.









9. Appl Biochem Biotechnol. 2009 Jan 23.
Effect of Ceramide on Mesenchymal Stem Cell Differentiation Toward Adipocytes.
Xu F, Yang CC, Gomillion C, Burg KJ.
Institute of Biological Interfaces of Engineering, Department of Bioengineering, College of Science and Engineering, Clemson University, Clemson, SC, 29634, USA.
Proinflammatory cytokines such as tumor necrosis factor (TNF) alpha are well known to inhibit adipocyte differentiation. TNF-alpha triggers ceramide synthesis through binding of TNF-alpha to its p55 receptor. Therefore, ceramide is implicated in many of the multiple signaling pathways initiated by TNF-alpha. In breast tissue engineering, it is important to know how to modulate adipocyte differentiation of the stem cells with exogenous additives like ceramide in vitro. We hypothesized that stem cell adipogenesis could be retained in TNF-alpha-treated preadipocytes in which ceramide synthesis was blocked and that exogenous ceramide could inhibit adipocyte differentiation. We first studied the effect of ceramide synthase inhibitor, Fumonisin B2, on the adipogenesis of murine mesenchymal stem cells (D1 cells), treated with TNF-alpha. We then studied the effect of specific exogenous C6-ceramide on D1 cell viability and differentiation. It was found that 1 ng/ml of TNF-alpha significantly inhibited D1 cell adipogenesis. Cells treated with 5 muM of Fumonisin B2 were able to undergo adipogenesis, even when treated with TNF-alpha. High concentrations of exogenous C6-ceramide (>50 muM) had an inhibitory effect, not only on the pre-confluent proliferation of the D1 cells but also on the post-confluent cell viability. High concentrations of C6-ceramide (>50 muM) also inhibited mitotic clonal expansion when D1 cell differentiation was induced by the addition of an adipogenic hormonal cocktail. C6-ceramide at low concentrations (10-25 muM) inhibited lipid production in D1 cells, demonstrated by decreased levels of both total triglyceride content and specific fatty acid composition percentages. Genetic expression of peroxisome proliferator-activated receptor (PPAR) gamma and aP2 in D1 cells was reduced by C6-ceramide treatment. CCAAT/enhancer-binding protein (C/EBP) beta levels in D1 cells were reduced by C6-ceramide treatment during early differentiation; PPARgamma and aP2 protein levels were reduced at terminal differentiation. C6-ceramide at lower concentrations also decreased lipid accumulation of differentiating D1 cells. Our results suggest that ceramide synthase inhibitor retains the adipogenic potential of TNF-alpha-treated mesenchymal stem cells, while exogenous ceramide at lower concentrations inhibit the adipogenesis of mesenchymal stem cells. Ceramide, therefore, could be a modulator candidate in breast tissue engineering strategies.



10. Eur J Cell Biol. 2009 Jan 22.
Expression of a functional epidermal growth factor receptor on human adipose-derived mesenchymal stem cells and its signaling mechanism.
Baer PC, Schubert R, Bereiter-Hahn J, Plößer M, Geiger H.
Division of Nephrology, Department of Internal Medicine III, Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany.
Adult stem cells act as a pluripotent source of regenerative cells during tissue injury. Despite expanded research in stem cell biology, understanding how growth and migration of adipose-derived adult mesenchymal stem cells (ASC) are governed by interactions with growth factors is very limited. One important property of ASC is the