Skip to main content

Advertisement

SpringerLink
Log in

Mesenchymal stromal cells (MSCs): science and f(r)iction

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Due to their multi-lineage differentiation capacity, support of haematopoiesis, immunomodulation and secretion of proregenerative factors, mesenchymal stem/stromal cells (MSCs) are in the focus of intense research since decades. The literature is replete with reports on their potential in preclinical model systems. However, the heterogeneity of the primary cell population as starting material and the diverse protocols for isolation and cultivation are hampering progress in their clinical application. Consensus on common standards and harmonised isolation and characterisation protocols are important to ensure safety and efficacy. This review focuses on the recent scientific evidence of clinically relevant properties and on the speculative cardiomyogenic and hepatic differentiation potential of MSCs. Special emphasis is put on the importance of standardisation and harmonisation in clinical-scale manufacturing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Caplan AI (1991) Mesenchymal stem cells. J Orthop Res 9:641–650

    Article  PubMed  CAS  Google Scholar 

  2. Salem HK, Thiemermann C (2010) Mesenchymal stromal cells: current understanding and clinical status. Stem Cells 28:585–596

    PubMed  CAS  Google Scholar 

  3. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    Article  PubMed  CAS  Google Scholar 

  4. Bernardo ME, Pagliara D, Locatelli F (2011) Mesenchymal stromal cell therapy: a revolution in Regenerative Medicine? Bone Marrow Transplant 47:164–171

    Article  PubMed  Google Scholar 

  5. Crisan M, Yap S, Casteilla L, Chen CW, Corselli M, Park TS, Andriolo G, Sun B, Zheng B, Zhang L et al (2008) A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell 3:301–313

    Article  PubMed  CAS  Google Scholar 

  6. Bieback K, Brinkmann I (2010) Mesenchymal stromal cells from human perinatal tissues: from biology to cell therapy. World J Stem Cells 2:81–92

    PubMed  Google Scholar 

  7. Wagner W, Wein F, Seckinger A, Frankhauser M, Wirkner U, Krause U, Blake J, Schwager C, Eckstein V, Ansorge W et al (2005) Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood. Exp Hematol 33:1402–1416

    Article  PubMed  CAS  Google Scholar 

  8. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24:1294–1301

    Article  PubMed  CAS  Google Scholar 

  9. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317

    Article  PubMed  CAS  Google Scholar 

  10. Giordano A, Galderisi U, Marino IR (2007) From the laboratory bench to the patient's bedside: an update on clinical trials with mesenchymal stem cells. J Cell Physiol 211:27–35

    Article  PubMed  CAS  Google Scholar 

  11. Koc ON, Gerson SL, Cooper BW, Dyhouse SM, Haynesworth SE, Caplan AI, Lazarus HM (2000) Rapid hematopoietic recovery after coinfusion of autologous-blood stem cells and culture-expanded marrow mesenchymal stem cells in advanced breast cancer patients receiving high-dose chemotherapy. J Clin Oncol 18:307–316

    PubMed  CAS  Google Scholar 

  12. Philippe B, Luc S, Valerie PB, Jerome R, Alessandra BR, Louis C (2010) Culture and use of mesenchymal stromal cells in phase I and II clinical trials. Stem Cells Int 2010:503593

    PubMed  Google Scholar 

  13. Bieback K, Kinzebach S, Karagianni M (2011) Translating research into clinical scale manufacturing of mesenchymal stromal cells. Stem Cells Int 2010:193519

    PubMed  Google Scholar 

  14. Bauer-Kreisel P, Goepferich A, Blunk T (2010) Cell-delivery therapeutics for adipose tissue regeneration. Adv Drug Deliv Rev 62:798–813

    Article  PubMed  CAS  Google Scholar 

  15. Zhang X, Zhang C, Tang T, Qu Z, Lou J, Dai K (2008) Immunomodulatory and osteogenic differentiation effects of mesenchymal stem cells by adenovirus-mediated coexpression of CTLA4Ig and BMP2. J Orthop Res 26:314–321

    Article  PubMed  CAS  Google Scholar 

  16. Lee SJ, Kang SW, Do HJ, Han I, Shin DA, Kim JH, Lee SH (2010) Enhancement of bone regeneration by gene delivery of BMP2/Runx2 bicistronic vector into adipose-derived stromal cells. Biomaterials 31:5652–5659

    Article  PubMed  CAS  Google Scholar 

  17. Brey D, Motlekar N, Diamond S, Mauck R, Garino J, Burdick J (2011) High-throughput screening of a small molecule library for promoters and inhibitors of mesenchymal stem cell osteogenic differentiation. Biotechnol Bioeng 108:163–237

    Article  PubMed  CAS  Google Scholar 

  18. Mendez-Ferrer S, Michurina TV, Ferraro F, Mazloom AR, Macarthur BD, Lira SA, Scadden DT, Ma'ayan A, Enikolopov GN, Frenette PS (2010) Mesenchymal and haematopoietic stem cells form a unique bone marrow niche. Nature 466:829–834

    Article  PubMed  CAS  Google Scholar 

  19. Cook MM, Futrega K, Osiecki M, Kabiri M, Kul B, Rice A, Atkinson K, Brooke G, Doran M (2012) Micromarrows-three-dimensional coculture of hematopoietic stem cells and mesenchymal stromal cells. Tissue Eng Part C Methods 18:319–328

    Article  PubMed  CAS  Google Scholar 

  20. Jing D, Fonseca AV, Alakel N, Fierro FA, Muller K, Bornhauser M, Ehninger G, Corbeil D, Ordemann R (2010) Hematopoietic stem cells in co-culture with mesenchymal stromal cells—modeling the niche compartments in vitro. Haematologica 95:542–550

    Article  PubMed  CAS  Google Scholar 

  21. Wagner W, Saffrich R, Wirkner U, Eckstein V, Blake J, Ansorge A, Schwager C, Wein F, Miesala K, Ansorge W et al (2005) Hematopoietic progenitor cells and cellular microenvironment: behavioral and molecular changes upon interaction. Stem Cells 23:1180–1191

    Article  PubMed  CAS  Google Scholar 

  22. Wagner W, Roderburg C, Wein F, Diehlmann A, Frankhauser M, Schubert R, Eckstein V, Ho AD (2007) Molecular and secretory profiles of human mesenchymal stromal cells and their abilities to maintain primitive hematopoietic progenitors. Stem Cells 25:2638–2647

    Article  PubMed  CAS  Google Scholar 

  23. Wagner W, Wein F, Roderburg C, Saffrich R, Faber A, Krause U, Schubert M, Benes V, Eckstein V, Maul H et al (2007) Adhesion of hematopoietic progenitor cells to human mesenchymal stem cells as a model for cell–cell interaction. Exp Hematol 35:314–325

    Article  PubMed  CAS  Google Scholar 

  24. Walenda T, Bork S, Horn P, Wein F, Saffrich R, Diehlmann A, Eckstein V, Ho AD, Wagner W (2010) Co-culture with mesenchymal stromal cells increases proliferation and maintenance of haematopoietic progenitor cells. J Cell Mol Med 14:337–350

    Article  PubMed  CAS  Google Scholar 

  25. Wuchter P, Boda-Heggemann J, Straub BK, Grund C, Kuhn C, Krause U, Seckinger A, Peitsch WK, Spring H, Ho AD et al (2007) Processus and recessus adhaerentes: giant adherens cell junction systems connect and attract human mesenchymal stem cells. Cell Tissue Res 328:499–514

    Article  PubMed  Google Scholar 

  26. Ho AD, Wagner W, Franke W (2008) Heterogeneity of mesenchymal stromal cell preparations. Cytotherapy 10:320–330

    Article  PubMed  CAS  Google Scholar 

  27. Wuchter P, Saffrich R, Wagner W, Wein F, Schubert MS, Eckstein V, Ho AD (2008) Human hematopoietic stem cells and leukemic cells form cadherin-catenin based junctional complexes with mesenchymal stromal cells. Blood 112:491

    Google Scholar 

  28. Wuchter P, Saffrich R, Giselbrecht S, Ho AD, Gottwald E (2011) Novel 3D-model for the hematopoietic stem cell niche using MSC in a KITChip based bioreactor. Blood (ASH Annual Meeting Abstracts) 118:1331

    Google Scholar 

  29. Le Blanc K, Tammik L, Sundberg B, Haynesworth SE, Ringden O (2003) Mesenchymal stem cells inhibit and stimulate mixed lymphocyte cultures and mitogenic responses independently of the major histocompatibility complex. Scand J Immunol 57:11–20

    Article  PubMed  Google Scholar 

  30. Krampera M (2011) Mesenchymal stromal cell 'licensing': a multistep process. Leukemia 25:1408–1414

    Article  PubMed  CAS  Google Scholar 

  31. Krampera M (2011) Mesenchymal stromal cells: more than inhibitory cells. Leukemia 25:565–566

    Article  PubMed  CAS  Google Scholar 

  32. Uccelli A, Moretta L, Pistoia V (2008) Mesenchymal stem cells in health and disease. Nat Rev Immunol 8:726–736

    Article  PubMed  CAS  Google Scholar 

  33. Tyndall A, Pistoia V (2009) Mesenchymal stem cells combat sepsis. Nat Med 15:18–20

    Article  PubMed  CAS  Google Scholar 

  34. Waterman RS, Tomchuck SL, Henkle SL, Betancourt AM (2010) A new mesenchymal stem cell (MSC) paradigm: polarization into a pro-inflammatory MSC1 or an Immunosuppressive MSC2 phenotype. PLoS One 5:e10088

    Article  PubMed  Google Scholar 

  35. Aggarwal S, Pittenger MF (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105:1815–1822

    Article  PubMed  CAS  Google Scholar 

  36. Le Blanc K, Ringden O (2005) Use of mesenchymal stem cells for the prevention of immune complications of hematopoietic stem cell transplantation. Haematologica 90:438

    PubMed  Google Scholar 

  37. Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M et al (2008) Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:1579–1586

    Article  PubMed  Google Scholar 

  38. Garcia-Olmo D, Herreros D, Pascual I, Pascual JA, Del-Valle E, Zorrilla J, De-La-Quintana P, Garcia-Arranz M, Pascual M (2009) Expanded adipose-derived stem cells for the treatment of complex perianal fistula: a phase II clinical trial. Dis Colon Rectum 52:79–86

    Article  PubMed  Google Scholar 

  39. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O et al (2010) Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 67:1187–1194

    Article  PubMed  Google Scholar 

  40. Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Yu Z, Li B, Xu C, Li Y et al (2008) The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 22:593–599

    Article  PubMed  CAS  Google Scholar 

  41. Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F 3rd (2011) Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells 29:11–19

    Article  PubMed  CAS  Google Scholar 

  42. Caplan AI, Correa D (2011) The MSC: an injury drugstore. Cell Stem Cell 9:11–15

    Article  PubMed  CAS  Google Scholar 

  43. Park KS, Kim YS, Kim JH, Choi B, Kim SH, Tan AH, Lee MS, Lee MK, Kwon CH, Joh JW et al (2010) Trophic molecules derived from human mesenchymal stem cells enhance survival, function, and angiogenesis of isolated islets after transplantation. Transplantation 89:509–517

    PubMed  CAS  Google Scholar 

  44. Gnecchi M, He H, Liang OD, Melo LG, Morello F, Mu H, Noiseux N, Zhang L, Pratt RE, Ingwall JS et al (2005) Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11:367–368

    Article  PubMed  CAS  Google Scholar 

  45. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE (2004) Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 109:1543–1549

    Article  PubMed  CAS  Google Scholar 

  46. Bonfield TL, Nolan Koloze MT, Lennon DP, Caplan AI (2010) Defining human mesenchymal stem cell efficacy in vivo. J Inflamm (Lond) 7:51

    Article  Google Scholar 

  47. Fatar M, Stroick M, Griebe M, Marwedel I, Kern S, Bieback K, Giesel FL, Zechmann C, Kreisel S, Vollmar F et al (2008) Lipoaspirate-derived adult mesenchymal stem cells improve functional outcome during intracerebral hemorrhage by proliferation of endogenous progenitor cells stem cells in intracerebral hemorrhages. Neurosci Lett 443:174–178

    Article  PubMed  CAS  Google Scholar 

  48. Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98:1076–1084

    Article  PubMed  CAS  Google Scholar 

  49. Dezawa M, Ishikawa H, Itokazu Y, Yoshihara T, Hoshino M, Takeda S, Ide C, Nabeshima Y (2005) Bone marrow stromal cells generate muscle cells and repair muscle degeneration. Science 309:314–317

    Article  PubMed  CAS  Google Scholar 

  50. Makino S, Fukuda K, Miyoshi S, Konishi F, Kodama H, Pan J, Sano M, Takahashi T, Hori S, Abe H et al (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103:697–705

    Article  PubMed  CAS  Google Scholar 

  51. Choi YH, Kurtz A, Stamm C (2011) Mesenchymal stem cells for cardiac cell therapy. Hum Gene Ther 22:3–17

    Article  PubMed  CAS  Google Scholar 

  52. Rickelt S (2012) Plakophilin-2: a cell-cell adhesion plaque molecule of selective and fundamental importance in cardiac functions and tumor cell growth. Cell Tissue Res. doi:10.1007/s00441-011-1314-3

  53. Borrmann CM, Grund C, Kuhn C, Hofmann I, Pieperhoff S, Franke WW (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. II. Colocalizations of desmosomal and fascia adhaerens molecules in the intercalated disk. Eur J Cell Biol 85:469–485

    Article  PubMed  CAS  Google Scholar 

  54. Franke WW, Borrmann CM, Grund C, Pieperhoff S (2006) The area composita of adhering junctions connecting heart muscle cells of vertebrates. I. Molecular definition in intercalated disks of cardiomyocytes by immunoelectron microscopy of desmosomal proteins. Eur J Cell Biol 85:69–82

    Article  PubMed  CAS  Google Scholar 

  55. Franke WW, Schumacher H, Borrmann CM, Grund C, Winter-Simanowski S, Schlechter T, Pieperhoff S, Hofmann I (2007) The area composita of adhering junctions connecting heart muscle cells of vertebrates. III. Assembly and disintegration of intercalated disks in rat cardiomyocytes growing in culture. Eur J Cell Biol 86:127–142

    Article  PubMed  CAS  Google Scholar 

  56. Moll R, Holzhausen HJ, Mennel HD, Kuhn C, Baumann R, Taege C, Franke WW (2006) The cardiac isoform of alpha-actin in regenerating and atrophic skeletal muscle, myopathies and rhabdomyomatous tumors: an immunohistochemical study using monoclonal antibodies. Virchows Arch 449:175–191

    Article  PubMed  CAS  Google Scholar 

  57. Pieperhoff S, Borrmann C, Grund C, Barth M, Rizzo S, Franke WW (2010) The area composita of adhering junctions connecting heart muscle cells of vertebrates. VII. The different types of lateral junctions between the special cardiomyocytes of the conduction system of ovine and bovine hearts. Eur J Cell Biol 89:365–378

    Article  PubMed  CAS  Google Scholar 

  58. Pieperhoff S, Franke WW (2007) The area composita of adhering junctions connecting heart muscle cells of vertebrates. IV. Coalescence and amalgamation of desmosomal and adhaerens junction components—late processes in mammalian heart development. Eur J Cell Biol 86:377–391

    Article  PubMed  CAS  Google Scholar 

  59. Pieperhoff S, Schumacher H, Franke WW (2008) The area composita of adhering junctions connecting heart muscle cells of vertebrates. V. The importance of plakophilin-2 demonstrated by small interference RNA-mediated knockdown in cultured rat cardiomyocytes. Eur J Cell Biol 87:399–411

    Article  PubMed  CAS  Google Scholar 

  60. Seeger TS, Frank D, Rohr C, Will R, Just S, Grund C, Lyon R, Luedde M, Koegl M, Sheikh F et al (2010) Myozap, a novel intercalated disc protein, activates serum response factor-dependent signaling and is required to maintain cardiac function in vivo. Circ Res 106:880–890

    Article  PubMed  CAS  Google Scholar 

  61. Gaebel R, Furlani D, Sorg H, Polchow B, Frank J, Bieback K, Wang W, Klopsch C, Ong LL, Li W et al (2011) Cell origin of human mesenchymal stem cells determines a different healing performance in cardiac regeneration. PLoS One 6:e15652

    Article  PubMed  CAS  Google Scholar 

  62. Choi YH, Nasseri B, Stamm C (2011) Cardiac cell therapy and bypass surgery. Curr Pharm Des 17:3348–3355

    PubMed  CAS  Google Scholar 

  63. Vulliet PR, Greeley M, Halloran SM, MacDonald KA, Kittleson MD (2004) Intra-coronary arterial injection of mesenchymal stromal cells and microinfarction in dogs. Lancet 363:783–784

    Article  PubMed  Google Scholar 

  64. Christ B, Dollinger MM (2011) The generation of hepatocytes from mesenchymal stem cells and engraftment into the liver. Curr Opin Org Transplant 16:69–75

    Google Scholar 

  65. Seo MJ, Suh SY, Bae YC, Jung JS (2005) Differentiation of human adipose stromal cells into hepatic lineage in vitro and in vivo. Biochem Biophys Res Commun 328:258–264

    Article  PubMed  CAS  Google Scholar 

  66. Aurich H, Sgodda M, Kaltwasser P, Vetter M, Weise A, Liehr T, Brulport M, Hengstler JG, Dollinger MM, Fleig WE et al (2009) Hepatocyte differentiation of mesenchymal stem cells from human adipose tissue in vitro promotes hepatic integration in vivo. Gut 58:570–581

    Article  PubMed  CAS  Google Scholar 

  67. Zemel R, Bachmetov L, Ad-El D, Abraham A, Tur-Kaspa R (2009) Expression of liver-specific markers in naive adipose-derived mesenchymal stem cells. Liver Int 29:1326–1337

    Article  PubMed  CAS  Google Scholar 

  68. Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Takayama T, Takahashi M et al (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106:756–763

    Article  PubMed  CAS  Google Scholar 

  69. Straub BK, Rickelt S, Zimbelmann R, Grund C, Kuhn C, Iken M, Ott M, Schirmacher P, Franke WW (2011) E-N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells. J Cell Biol 195:873–887

    Article  PubMed  CAS  Google Scholar 

  70. Haridass D, Yuan Q, Becker PD, Cantz T, Iken M, Rothe M, Narain N, Bock M, Norder M, Legrand N et al (2009) Repopulation efficiencies of adult hepatocytes, fetal liver progenitor cells, and embryonic stem cell-derived hepatic cells in albumin-promoter-enhancer urokinase-type plasminogen activator mice. Am J Pathol 175:1483–1492

    Article  PubMed  CAS  Google Scholar 

  71. Mohamadnejad M, Pournasr B, Bagheri M, Aghdami N, Shahsavani M, Hosseini LA, Taghiabadi E, Azizi H, Heidari I, Akhlaghpoor S et al (2010) Transplantation of allogeneic bone marrow mesenchymal stromal cell-derived hepatocyte-like cells in homozygous familial hypercholesterolemia. Cytotherapy 12:566–568

    Article  PubMed  Google Scholar 

  72. Kanazawa H, Fujimoto Y, Teratani T, Iwasaki J, Kasahara N, Negishi K, Tsuruyama T, Uemoto S, Kobayashi E (2011) Bone marrow-derived mesenchymal stem cells ameliorate hepatic ischemia reperfusion injury in a rat model. PLoS One 6:e19195

    Article  PubMed  CAS  Google Scholar 

  73. van Poll D, Parekkadan B, Cho CH, Berthiaume F, Nahmias Y, Tilles AW, Yarmush ML (2008) Mesenchymal stem cell-derived molecules directly modulate hepatocellular death and regeneration in vitro and in vivo. Hepatology 47:1634–1643

    Article  PubMed  Google Scholar 

  74. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  PubMed  CAS  Google Scholar 

  75. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131:861–872

    Article  PubMed  CAS  Google Scholar 

  76. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318:1917–1920

    Article  PubMed  CAS  Google Scholar 

  77. Park IH, Zhao R, West JA, Yabuuchi A, Huo H, Ince TA, Lerou PH, Lensch MW, Daley GQ (2008) Reprogramming of human somatic cells to pluripotency with defined factors. Nature 451:141–146

    Article  PubMed  CAS  Google Scholar 

  78. Bieback K, Schallmoser K, Klüter H, Strunk D (2008) Clinical protocols for the isolation and expansion of mesenchymal stromal cells. Transfus Med Hemother 35:286–294

    PubMed  Google Scholar 

  79. Shibata K, Aoyama T, Shima Y, Fukiage K, Otsuka S, Furu M, Kohno Y, Ito K, Fujibayashi S, Neo M et al (2007) Expression of the p16INK4A gene is associated closely with senescence of human mesenchymal stem cells and is potentially silenced by DNA methylation during in vitro expansion. Stem cells (Dayton, Ohio) 25:2371–2453

    Article  CAS  Google Scholar 

  80. Wagner W, Horn P, Castoldi M, Diehlmann A, Bork S, Saffrich R, Benes V, Blake J, Pfister S, Eckstein V et al (2008) Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One 3:e2213

    Google Scholar 

  81. Bieback K, Hecker A, Schlechter T, Hofmann I, Brousos N, Redmer T, Besser D, Klüter H, Müller AM, Becker M (2012) Replicative aging and differentiation potential of human adipose tissue-derived mesenchymal stromal cells expanded in pooled human or fetal bovine serum. Cytotherapy 14:570–583

    Article  PubMed  CAS  Google Scholar 

  82. Wagner W, Feldmann RE Jr, Seckinger A, Maurer MH, Wein F, Blake J, Krause U, Kalenka A, Burgers HF, Saffrich R et al (2006) The heterogeneity of human mesenchymal stem cell preparations—evidence from simultaneous analysis of proteomes and transcriptomes. Exp Hematol 34:536–548

    Article  PubMed  CAS  Google Scholar 

  83. Wagner W, Ho AD (2007) Mesenchymal stem cell preparations—comparing apples and oranges. Stem Cell Rev 3:239–248

    Article  PubMed  Google Scholar 

  84. Tarte K, Gaillard J, Lataillade JJ, Fouillard L, Becker M, Mossafa H, Tchirkov A, Rouard H, Henry C, Splingard M et al (2010) Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood 115:1549–1553

    Article  PubMed  CAS  Google Scholar 

  85. Ra JC, Shin IS, Kim SH, Kang SK, Kang BC, Lee HY, Kim YJ, Jo JY, Yoon EJ, Choi HJ et al (2011) Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev 20:1297–1308

    Article  PubMed  CAS  Google Scholar 

  86. Mannello F, Tonti GA (2007) Concise review: no breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold! Stem Cells 25:1603–1609

    Article  PubMed  CAS  Google Scholar 

  87. Bieback K, Ha VA, Hecker A, Grassl M, Kinzebach S, Solz H, Sticht C, Klüter H, Bugert P (2010) Altered gene expression in human adipose stem cells cultured with fetal bovine serum compared to human supplements. Tissue Eng Part A 16:3467–3484

    Article  PubMed  CAS  Google Scholar 

  88. Bieback K, Hecker A, Kocaomer A, Lannert H, Schallmoser K, Strunk D, Klüter H (2009) Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells 27:2331–2341

    Article  PubMed  CAS  Google Scholar 

  89. Kocaoemer A, Kern S, Klüter H, Bieback K (2007) Human AB serum and thrombin-activated platelet-rich plasma are suitable alternatives to fetal calf serum for the expansion of mesenchymal stem cells from adipose tissue. Stem Cells 25:1270–1278

    Article  PubMed  CAS  Google Scholar 

  90. Perez-Simon JA, Lopez-Villar O, Andreu EJ, Rifon J, Muntion S, Campelo MD, Sanchez-Guijo FM, Martinez C, Valcarcel D, Canizo CD (2011) Mesenchymal stem cells expanded in vitro with human serum for the treatment of acute and chronic graft-versus-host disease: results of a phase I/II clinical trial. Haematologica 96:1072–1076

    Article  PubMed  Google Scholar 

  91. Honmou O, Houkin K, Matsunaga T, Niitsu Y, Ishiai S, Onodera R, Waxman SG, Kocsis JD (2011) Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke. Brain 134:1790–1807

    Article  PubMed  Google Scholar 

  92. von Bonin M, Stolzel F, Goedecke A, Richter K, Wuschek N, Holig K, Platzbecker U, Illmer T, Schaich M, Schetelig J et al (2009) Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 43:245–251

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by research funds of the German Federal Ministry of Education and Research (START-MSC 1 and 2: 01GN0531 and 01GN0939). We would like to thank Daniela Griffiths for proofreading.

Author disclosure statement

No competing financial interests exist.

Author information

Authors and Affiliations

  1. Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, German Red Cross Blood Service Baden-Württemberg-Hessen, Heidelberg University, Mannheim, Germany

    Karen Bieback & Harald Klüter

  2. Department of Medicine V, Heidelberg University, Heidelberg, Germany

    Patrick Wuchter & Anthony D. Ho

  3. Max-Delbrück-Center for Molecular Medicine, Signaling in Embryonic Stem Cells, Berlin, Germany

    Daniel Besser

  4. Helmholtz Group for Cell Biology, German Cancer Research Center (DKFZ), Heidelberg, Germany

    Werner Franke

  5. MSZ in the Center for Experimental Molecular Medicine (ZEMM), University of Würzburg, Würzburg, Germany

    Matthias Becker & Albrecht Müller

  6. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School and Twincore Centre for Experimental and Clinical Infection Research, Hannover, Germany

    Michael Ott & Martin Pacher

  7. Centre for Biomaterial Development, Institute of Polymer Research, Helmholtz Zentrum Geesthacht, Teltow, Germany

    Nan Ma

  8. Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany

    Christof Stamm

Authors
  1. Karen Bieback
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick Wuchter
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Besser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Werner Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthias Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Michael Ott
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Martin Pacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Nan Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Christof Stamm
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Harald Klüter
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Albrecht Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Anthony D. Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

for the START-MSC consortium

Corresponding author

Correspondence to Karen Bieback.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bieback, K., Wuchter, P., Besser, D. et al. Mesenchymal stromal cells (MSCs): science and f(r)iction. J Mol Med 90, 773–782 (2012). https://doi.org/10.1007/s00109-012-0915-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-012-0915-y

Keywords

Search

Navigation