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Expansion of Mesenchymal Stem/Stromal Cells under Xenogenic-Free Culture Conditions

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Mesenchymal Stem Cells - Basics and Clinical Application I

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 129))

Abstract

Mesenchymal Stem/Stromal cells (MSCs) are increasingly applied in cell-based regenerative medicine. To yield clinically relevant cell doses, ex vivo expansion of MSCs is required to be compliant with good manufacturing practice (GMP) guidelines. A lack of standardization and harmonization seems to hamper rapid progress in the translational phase. Most protocols still use fetal bovine serum (FBS) to expand MSCs. However, the high lot-to-lot variability, risk of contamination and immunization call for xenogenic-free culture conditions. Chemically defined media are the ultimate achievement in terms of standardization. These media, however, need to maintain all key cellular and therapy-relevant features of MSCs. Because of the numerous constituents of FBS, the development of such chemically defined media with an optimal composition of the few essential factors is only beginning. Meanwhile, various human blood-derived components are under investigation, including human plasma, human serum, human umbilical cord blood serum and human platelet derivatives such as platelet lysate.

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References

  1. Agata H, Watanabe N, Ishii Y et al (2009) Feasibility and efficacy of bone tissue engineering using human bone marrow stromal cells cultivated in serum-free conditions. Biochem Biophys Res Commun 382:353–358

    CAS  Google Scholar 

  2. Arthur A, Zannettino A, Gronthos S (2009) The therapeutic applications of multipotential mesenchymal/stromal stem cells in skeletal tissue repair. J Cell Physiol 218:237–245

    CAS  Google Scholar 

  3. Astori G, Soncin S, Lo Cicero V et al (2010) Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products. Am J Transl Res 2:285–295

    Google Scholar 

  4. Avanzini MA, Bernardo ME, Cometa AM et al (2009) Generation of mesenchymal stromal cells in the presence of platelet lysate: a phenotypic and functional comparison of umbilical cord blood- and bone marrow-derived progenitors. Haematologica 94:1649–1660

    CAS  Google Scholar 

  5. Belford DA, Rogers ML, Regester GO et al (1995) Milk-derived growth factors as serum supplements for the growth of fibroblast and epithelial cells. In Vitro Cell Dev Biol Anim 31:752–760

    CAS  Google Scholar 

  6. Bernardo ME, Avanzini MA, Perotti C et al (2007) Optimization of in vitro expansion of human multipotent mesenchymal stromal cells for cell-therapy approaches: further insights in the search for a fetal calf serum substitute. J Cell Physiol 211:121–130

    CAS  Google Scholar 

  7. Bernardo ME, Cometa AM, Pagliara D et al (2011) Ex vivo expansion of mesenchymal stromal cells. Best Pract Res Clin Haematol 24:73–81

    CAS  Google Scholar 

  8. Bernardo ME, Pagliara D, Locatelli F (2012) Mesenchymal stromal cell therapy: a revolution in regenerative medicine? Bone Marrow Transplant 47:164–171

    CAS  Google Scholar 

  9. Bieback K, Ha VA, Hecker A et al (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

    CAS  Google Scholar 

  10. Bieback K, Hecker A, Kocaomer A et al (2009) Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells 27:2331–2341

    CAS  Google Scholar 

  11. Bieback K, Hecker A, Schlechter T et al (2012) Replicative aging and differentiation potential of human adipose tissue-derived mesenchymal stromal cells expanded in pooled human or fetal bovine serum. Cytotherapy

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  14. Breitbach M, Bostani T, Roell W et al (2007) Potential risks of bone marrow cell transplantation into infarcted hearts. Blood 110:1362–1369

    CAS  Google Scholar 

  15. Bruder SP, Jaiswal N, Haynesworth SE (1997) Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. J Cell Biochem 64:278–294

    CAS  Google Scholar 

  16. Brunner D, Frank J, Appl H et al (2010) Serum-free cell culture: the serum-free media interactive online database. ALTEX 27:53–62

    Google Scholar 

  17. Burns JS, Abdallah BM, Guldberg P et al (2005) Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells. Cancer Res 65:3126–3135

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  19. Caplan AI (1994) The mesengenic process. Clin Plast Surg 21:429–435

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  21. Chase LG, Lakshmipathy U, Solchaga LA, Rao MS, Vemuri MC (2010) A novel serum-free medium for the expansion of human mesenchymal stem cells: Stem Cell Res Ther 1:8

    Google Scholar 

  22. Chatzistamatiou T, Kokkinos T, Papassavas A , Stavropoulos-Giokas C (2007) Cord blood serum: an efficient media supplement for maintaining cord blood derived mesenchymal stem cells cultures. Tissue Antigens. 65:524−525

    Google Scholar 

  23. Cheng H, Qiu L, Ma J et al (2011) Replicative senescence of human bone marrow and umbilical cord derived mesenchymal stem cells and their differentiation to adipocytes and osteoblasts. Mol Biol Rep 38:5161–5168

    CAS  Google Scholar 

  24. Crespo-Diaz R, Behfar A, Butler GW et al (2011) Platelet lysate consisting of a natural repair proteome supports human mesenchymal stem cell proliferation and chromosomal stability. Cell Transplant 20:797–811

    Google Scholar 

  25. Dahl JA, Duggal S, Coulston N et al (2008) Genetic and epigenetic instability of human bone marrow mesenchymal stem cells expanded in autologous serum or fetal bovine serum. Int J Dev Biol 52:1033–1042

    CAS  Google Scholar 

  26. Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884

    CAS  Google Scholar 

  27. Dominici M, Le Blanc K, Mueller I et al (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy 8:315–317

    CAS  Google Scholar 

  28. Doucet C, Ernou I, Zhang Y et al (2005) Platelet lysates promote mesenchymal stem cell expansion: a safety substitute for animal serum in cell-based therapy applications. J Cell Physiol 205:228–236

    CAS  Google Scholar 

  29. Dugrillon A, Eichler H, Kern S et al (2002) Autologous concentrated platelet-rich plasma (cprp) for local application in bone regeneration. Int J Oral Maxillofac Surg 31:615–619

    CAS  Google Scholar 

  30. Eastment CT, Sirbasku DA (1980) Human platelet lysate contains growth factor activities for established cell lines derived from various tissues of several species. In Vitro 16:694–705

    CAS  Google Scholar 

  31. EMEA (2003) Note for guidance on the use of bovine serum in the manufacture of human medicinal products. EMEA CPMP/BWP/1793/02.

    Google Scholar 

  32. Fan X, Liu T, Liu Y et al (2009) Optimization of primary culture condition for mesenchymal stem cells derived from umbilical cord blood with factorial design. Biotechnol Prog 25:499–507

    CAS  Google Scholar 

  33. Fekete N, Gadelorge M, Furst D, Maurer C, Dausend J, Fleury-Cappellesso S, Mailander V, Lotfi R, Ignatius A, Sensebe L, Bourin P, Schrezenmeier H, Rojewski MT (2012) Platelet lysate from whole blood-derived pooled platelet concentrates and apheresis-derived platelet concentrates for the isolation and expansion of human bone marrow mesenchymal stromal cells: production process, content and identification of active components. Cytotherapy 14:540–554

    CAS  Google Scholar 

  34. Filipic B, Shehata M, Toth S et al (2002) Novel serum replacement based on bovine ocular fluid: a useful tool for cultivation of different animal cells in vitro. ALTEX 19:15–20

    Google Scholar 

  35. Friedenstein AJ, Deriglasova UF, Kulagina NN et al (1974) Precursors for fibroblasts in different populations of hematopoietic cells as detected by the in vitro colony assay method. Exp Hematol 2:83–92

    CAS  Google Scholar 

  36. Friedenstein AJ, Petrakova KV, Kurolesova AI et al (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6:230–247

    CAS  Google Scholar 

  37. Gastens MH, Goltry K, Prohaska W et al (2007) Good manufacturing practice-compliant expansion of marrow-derived stem and progenitor cells for cell therapy. Cell Transplant 16:685–696

    Google Scholar 

  38. Gronthos S, Simmons PJ (1995) The growth factor requirements of stro-1-positive human bone marrow stromal precursors under serum-deprived conditions in vitro. Blood 85:929–940

    CAS  Google Scholar 

  39. Gruber R, Karreth F, Kandler B et al (2004) Platelet-released supernatants increase migration and proliferation, and decrease osteogenic differentiation of bone marrow-derived mesenchymal progenitor cells under in vitro conditions. Platelets 15:29–35

    CAS  Google Scholar 

  40. Hartmann I, Hollweck T, Haffner S et al (2010) Umbilical cord tissue-derived mesenchymal stem cells grow best under gmp-compliant culture conditions and maintain their phenotypic and functional properties. J Immunol Methods 363:80–89

    CAS  Google Scholar 

  41. Heiskanen A, Satomaa T, Tiitinen S et al (2007) N-Glycolylneuraminic acid xenoantigen contamination of human embryonic and mesenchymal stem cells is substantially reversible. Stem Cells 25:197–202

    CAS  Google Scholar 

  42. Honn KV, Singley JA, Chavin W (1975) Fetal bovine serum: a multivariate standard. Proc Soc Exp Biol Med 149:344–347

    CAS  Google Scholar 

  43. Horwitz EM, Le Blanc K, Dominici M et al (2005) Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy 7:393–395

    CAS  Google Scholar 

  44. Horwitz EM, Prockop DJ, Fitzpatrick LA et al (1999) Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med 5:309–313

    CAS  Google Scholar 

  45. Horwitz EM, Prockop DJ, Gordon PL et al (2001) Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 97:1227–1231

    CAS  Google Scholar 

  46. Hosseinkhani H, Hosseinkhani M, Kobayashi H (2006) Proliferation and differentiation of mesenchymal stem cells using self-assembled peptide amphiphile nanofibers. Biomed Mater 1:8–15

    CAS  Google Scholar 

  47. Ito K, Yamada Y, Nagasaka T et al (2005) Osteogenic potential of injectable tissue-engineered bone: a comparison among autogenous bone, bone substitute (bio-Oss), platelet-rich plasma, and tissue-engineered bone with respect to their mechanical properties and histological findings. J Biomed Mater Res A 73:63–72

    Google Scholar 

  48. Janetzko K, Bugert P (2011) Pathogen reduction in blood products: what’s behind these techniques? Transfus Med Hemother 38:5–6

    Google Scholar 

  49. Jung J, Moon N, Ahn JY et al (2009) Mesenchymal stromal cells expanded in human allogenic cord blood serum display higher self-renewal and enhanced osteogenic potential. Stem Cells Dev 18:559–571

    CAS  Google Scholar 

  50. Kilian O, Flesch I, Wenisch S et al (2004) Effects of platelet growth factors on human mesenchymal stem cells and human endothelial cells in vitro. Eur J Med Res 9:337–344

    CAS  Google Scholar 

  51. Klopp AH, Gupta A, Spaeth E et al (2011) Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells 29:11–19

    CAS  Google Scholar 

  52. Kobayashi T, Watanabe H, Yanagawa T et al (2005) Motility and growth of human bone-marrow mesenchymal stem cells during ex vivo expansion in autologous serum. J Bone Joint Surg Br 87:1426–1433

    CAS  Google Scholar 

  53. Koc ON, Gerson SL, Cooper BW et al (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

    CAS  Google Scholar 

  54. Kocaoemer A, Kern S, Klüter H et al (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

    CAS  Google Scholar 

  55. Ksiazek K (2009) A comprehensive review on mesenchymal stem cell growth and senescence. Rejuvenation Res 12:105–116

    CAS  Google Scholar 

  56. Lange C, Cakiroglu F, Spiess AN et al (2007) Accelerated and safe expansion of human mesenchymal stromal cells in animal serum-free medium for transplantation and regenerative medicine. J Cell Physiol 213:18–26

    CAS  Google Scholar 

  57. Lazennec G, Jorgensen C (2008) Concise review: adult multipotent stromal cells and cancer: risk or benefit? Stem Cells 26:1387–1394

    CAS  Google Scholar 

  58. Le Blanc K, Frassoni F, Ball L 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

    Google Scholar 

  59. Le Blanc K, Rasmusson I, Sundberg B et al (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363:1439–1441

    Google Scholar 

  60. Le Blanc K, Samuelsson H, Gustafsson B et al (2007) Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells. Leukemia 21:1733–1738

    Google Scholar 

  61. Le Blanc K, Tammik L, Sundberg B et al (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

    Google Scholar 

  62. Lepperdinger G, Brunauer R, Jamnig A et al (2008) Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies? Exp Gerontol 43:1018–1023

    CAS  Google Scholar 

  63. Lin HT, Tarng YW, Chen YC et al (2005) Using human plasma supplemented medium to cultivate human bone marrow-derived mesenchymal stem cell and evaluation of its multiple-lineage potential. Transplant Proc 37:4504–4505

    Google Scholar 

  64. 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

    CAS  Google Scholar 

  65. Marx RE (2004) Platelet-rich plasma: evidence to support its use. J Oral Maxillofac Surg 62:489–496

    Google Scholar 

  66. Mizuno N, Shiba H, Ozeki Y et al (2006) Human autologous serum obtained using a completely closed bag system as a substitute for foetal calf serum in human mesenchymal stem cell cultures. Cell Biol Int 30:521–524

    CAS  Google Scholar 

  67. Muller AM, Davenport M, Verrier S et al (2009) Platelet lysate as a serum substitute for 2D static and 3D perfusion culture of stromal vascular fraction cells from human adipose tissue. Tissue Eng Part A 15:869–875

    CAS  Google Scholar 

  68. Ng F, Boucher S, Koh S et al (2008) PDGF, TGF-beta, and FGF signaling is important for differentiation and growth of mesenchymal stem cells (MSCs): transcriptional profiling can identify markers and signaling pathways important in differentiation of MSCs into adipogenic, chondrogenic, and osteogenic lineages. Blood 112:295–307

    CAS  Google Scholar 

  69. Nimura A, Muneta T, Koga H et al (2008) Increased proliferation of human synovial mesenchymal stem cells with autologous human serum: comparisons with bone marrow mesenchymal stem cells and with fetal bovine serum. Arthritis Rheum 58:501–510

    CAS  Google Scholar 

  70. Pakkanen R (1994) Bovine colostrum ultrafiltrate supplemented with adult bovine serum and transferrin: an effective fbs substitute for cultivation of Vero and CHO-K1 cells. In Vitro Cell Dev Biol Anim 30A:295–299

    CAS  Google Scholar 

  71. Pazos P, Boveri M, Gennari A et al (2004) Culturing cells without serum: lessons learnt using molecules of plant origin. ALTEX 21:67–72

    Google Scholar 

  72. Perez-Ilzarbe M, Diez-Campelo M, Aranda P et al (2009) Comparison of ex vivo expansion culture conditions of mesenchymal stem cells for human cell therapy. Transfusion 49:1901–1910

    CAS  Google Scholar 

  73. Pevsner-Fischer M, Levin S, Zipori D (2011) The origins of mesenchymal stromal cell heterogeneity. Stem Cell Rev 7:560–568

    CAS  Google Scholar 

  74. Phadnis SM, Joglekar MV, Venkateshan V et al (2006) Human umbilical cord blood serum promotes growth, proliferation, as well as differentiation of human bone marrow-derived progenitor cells. In Vitro Cell Dev Biol Anim 42:283–286

    Google Scholar 

  75. Phermthai T, Odglun Y, Chuenwattana P et al (2011) Successful derivation and characteristics of xeno-free mesenchymal stem cell lines from human amniotic fluid generated under allogenic cord blood serum supplementation. Tissue Eng Regen Med 8:216–223

    Google Scholar 

  76. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147

    CAS  Google Scholar 

  77. Prockop DJ (2007) “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin Pharmacol Ther 82:241–243

    CAS  Google Scholar 

  78. Prockop DJ, Brenner M, Fibbe WE et al (2010) Defining the risks of mesenchymal stromal cell therapy. Cytotherapy 12:576–578

    Google Scholar 

  79. Ramasamy R, Lam EW, Soeiro I et al (2007) Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth. Leukemia 21:304–310

    CAS  Google Scholar 

  80. Schafer R, Schnaidt M, Klaffschenkel RA et al (2011) Expression of blood group genes by mesenchymal stem cells. Br J Haematol 153:520–528

    Google Scholar 

  81. Schallmoser K, Bartmann C, Rohde E et al (2007) Human platelet lysate can replace fetal bovine serum for clinical-scale expansion of functional mesenchymal stromal cells. Transfusion 47:1436–1446

    CAS  Google Scholar 

  82. Schallmoser K, Rohde E, Bartmann C et al (2009) Platelet-derived growth factors for GMP-compliant propagation of mesenchymal stromal cells. Biomed Mater Eng 19:271–276

    Google Scholar 

  83. Selvaggi TA, Walker RE, Fleisher TA (1997) Development of antibodies to fetal calf serum with arthus-like reactions in human immunodeficiency virus-infected patients given syngeneic lymphocyte infusions. Blood 89:776–779

    CAS  Google Scholar 

  84. Sensebe L (2008) Clinical grade production of mesenchymal stem cells. Biomed Mater Eng 18:S3–S10

    CAS  Google Scholar 

  85. Sensebe L, Krampera M, Schrezenmeier H, Bourin P, Giordano R (2010) Mesenchymal stem cells for clinical application. Vox Sang 98:93–107

    CAS  Google Scholar 

  86. Senzel L, Gnatenko DV, Bahou WF (2009) The platelet proteome. Curr Opin Hematol 16:329–333

    CAS  Google Scholar 

  87. Shahdadfar A, Fronsdal K, Haug T et al (2005) In vitro expansion of human mesenchymal stem cells: choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability. Stem cells 23:1357–1366

    CAS  Google Scholar 

  88. Shetty P, Bharucha K, Tanavde V (2007) Human umbilical cord blood serum can replace fetal bovine serum in the culture of mesenchymal stem cells. Cell Biol Int 31:293–298

    CAS  Google Scholar 

  89. Shibata KR, Aoyama T, Shima Y 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 25:2371–2382

    CAS  Google Scholar 

  90. Shih DT, Chen JC, Chen WY et al (2011) Expansion of adipose tissue mesenchymal stromal progenitors in serum-free medium supplemented with virally inactivated allogeneic human platelet lysate. Transfusion 51:770–778

    Google Scholar 

  91. Song HJ, Zhang P, Guo XJ et al (2009) The proteomic analysis of human neonatal umbilical cord serum by mass spectrometry. Acta Pharmacologica Sinica 30:1550–1558

    CAS  Google Scholar 

  92. Spees JL, Gregory CA, Singh H et al (2004) Internalized antigens must be removed to prepare hypoimmunogenic mesenchymal stem cells for cell and gene therapy. Mol Ther 9:747–756

    CAS  Google Scholar 

  93. Stute N, Holtz K, Bubenheim M et al (2004) Autologous serum for isolation and expansion of human mesenchymal stem cells for clinical use. Exp Hematol 32:1212–1225

    CAS  Google Scholar 

  94. Sundin M, Ringden O, Sundberg B et al (2007) No alloantibodies against mesenchymal stromal cells, but presence of anti-fetal calf serum antibodies, after transplantation in allogeneic hematopoietic stem cell recipients. Haematologica 92:1208–1215

    CAS  Google Scholar 

  95. Tarte K, Gaillard J, Lataillade JJ, Fouillard L, Becker M, Mossafa H, Tchirkov A, Rouard H, Henry C, Splingard M, Dulong J, Monnier D, Gourmelon P, Gorin NC, Sensebe L (2010) Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation. Blood 115:1549–1553

    CAS  Google Scholar 

  96. Tekkatte C, Gunasingh GP, Cherian KM et al (2011) “Humanized” Stem cell culture techniques: the animal serum controversy. Stem Cells Int 2011:504723

    Google Scholar 

  97. Turnovcova K, Ruzickova K, Vanecek V et al (2009) Properties and growth of human bone marrow mesenchymal stromal cells cultivated in different media. Cytotherapy 11:874–885

    CAS  Google Scholar 

  98. van der Valk J, Brunner D, De Smet K et al (2010) Optimization of chemically defined cell culture media–replacing fetal bovine serum in mammalian in vitro methods. Toxicol In Vitro 24:1053–1063

    Google Scholar 

  99. von Bonin M, Stolzel F, Goedecke A et al (2009) Treatment of refractory acute GVHD with third-party MSC expanded in platelet lysate-containing medium. Bone Marrow Transplant 43:245–251

    Google Scholar 

  100. Weissman IL (2000) Translating stem and progenitor cell biology to the clinic: barriers and opportunities. Science 287:1442–1446

    CAS  Google Scholar 

  101. Wessman SJ, Levings RL (1999) Benefits and risks due to animal serum used in cell culture production. Dev Biol Stand 99:3–8

    CAS  Google Scholar 

  102. Yang C, Frei H, Rossi FM et al (2009) The differential in vitro and in vivo responses of bone marrow stromal cells on novel porous gelatin-alginate scaffolds. J Tissue Eng Regen Med 3:601–614

    CAS  Google Scholar 

  103. Zeisberger SM, Schulz JC, Mairhofer M et al (2011) Biological and physicochemical characterization of a serum- and xeno-free chemically defined cryopreservation procedure for adult human progenitor cells. Cell transplant 20:1241–1257

    Google Scholar 

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Acknowledgments

This work was supported by research funds from the German Federal Ministry of Education and Research (START-MSC: 01GN0531 and 01GN0939) and a project commissioned by the European Community (CASCADE: FP7-223236).

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Kinzebach, S., Bieback, K. (2012). Expansion of Mesenchymal Stem/Stromal Cells under Xenogenic-Free Culture Conditions. In: Weyand, B., Dominici, M., Hass, R., Jacobs, R., Kasper, C. (eds) Mesenchymal Stem Cells - Basics and Clinical Application I. Advances in Biochemical Engineering/Biotechnology, vol 129. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2012_134

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