Langenbeck's Archives of Surgery

, Volume 396, Issue 4, pp 489–497 | Cite as

Mesenchymal stem cells and progenitor cells in connective tissue engineering and regenerative medicine: is there a future for transplantation?

  • Andres Hilfiker
  • Cornelia Kasper
  • Ralf Hass
  • Axel Haverich
Review Article

Abstract

Purpose

Transplantation surgery suffers from a shortage of donor organs worldwide. Cell injection and tissue engineering (TE), thus emerge as alternative therapy options. The purpose of this article is to review the progress of TE technology, focusing on mesenchymal stem cells (MSC) as a cell source for artificial functional tissue.

Results

MSC from many different sources can be minimally invasively harvested: peripheral blood, fat tissue, bone marrow, amniotic fluid, cord blood. In comparison to embryonic stem cells (ESC), there are no ethical concerns; MSC can be extracted from autologous or allogenic tissue and cause an immune modulatory effect by suppressing the graft-versus-host reaction (GvHD). Furthermore, MSC do not develop into teratomas when transplanted, a consequence observed with ESC and iPS cells.

Conclusion

MSC as multipotent cells are capable of differentiating into mesodermal and non-mesodermal lineages. However, further studies must be performed to elucidate the differentiation capacity of MSC from different sources, and to understand the involved pathways and processes. Already, MSC have been successfully applied in clinical trials, e.g., to heal large bone defects, cartilage lesions, spinal cord injuries, cardiovascular diseases, hematological pathologies, osteogenesis imperfecta, and GvHD. A detailed understanding of the behavior and homing of MSC is desirable to enlarge the clinical application spectrum of MSC towards the in vitro generation of functional tissue for implantation, for example, resilient cartilage, contractile myocardial replacement tissue, and bioartificial heart valves.

Keywords

Tissue engineering MSC Connective tissue Transplantation 

References

  1. 1.
    Calne RY, Rolles K, White DJ, Thiru S, Evans DB, McMaster P, Dunn DC, Craddock GN, Henderson RG, Aziz S, Lewis P (1979) Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases, and 2 livers. Lancet 2(8151):1033–1036PubMedGoogle Scholar
  2. 2.
    Fuchs JR, Nasseri BA, Vacanti JP (2001) Tissue engineering: a 21st century solution to surgical reconstruction. Ann Thorac Surg 72(2):577–591PubMedGoogle Scholar
  3. 3.
    Lutter G, Metzner A, Jahnke T, Bombien R, Boldt J, Iino K, Cremer J, Stock UA (2010) Percutaneous tissue-engineered pulmonary valved stent implantation. Ann Thorac Surg 89(1):259–263. doi:10.1016/j.athoracsur.2009.06.048 PubMedGoogle Scholar
  4. 4.
    Stock UA, Vacanti JP, Mayer JE Jr, Wahlers T (2002) Tissue engineering of heart valves—current aspects. Thorac Cardiovasc Surg 50(3):184–193. doi:10.1055/s-2002-32406 PubMedGoogle Scholar
  5. 5.
    Baraki H, Tudorache I, Braun M, Hoffler K, Gorler A, Lichtenberg A, Bara C, Calistru A, Brandes G, Hewicker-Trautwein M, Hilfiker A, Haverich A, Cebotari S (2009) Orthotopic replacement of the aortic valve with decellularized allograft in a sheep model. Biomaterials 30(31):6240–6246. doi:10.1016/j.biomaterials.2009.07.068 PubMedGoogle Scholar
  6. 6.
    Lichtenberg A, Tudorache I, Cebotari S, Suprunov M, Tudorache G, Goerler H, Park JK, Hilfiker-Kleiner D, Ringes-Lichtenberg S, Karck M, Brandes G, Hilfiker A, Haverich A (2006) Preclinical testing of tissue-engineered heart valves re-endothelialized under simulated physiological conditions. Circulation 114(1 Suppl):I559–I565. doi:10.1161/CIRCULATIONAHA.105.001206 PubMedGoogle Scholar
  7. 7.
    Cebotari S, Lichtenberg A, Tudorache I, Hilfiker A, Mertsching H, Leyh R, Breymann T, Kallenbach K, Maniuc L, Batrinac A, Repin O, Maliga O, Ciubotaru A, Haverich A (2006) Clinical application of tissue engineered human heart valves using autologous progenitor cells. Circulation 114(1 Suppl):I132–I137. doi:10.1161/CIRCULATIONAHA.105.001065 PubMedGoogle Scholar
  8. 8.
    Schmidt D, Dijkman PE, Driessen-Mol A, Stenger R, Mariani C, Puolakka A, Rissanen M, Deichmann T, Odermatt B, Weber B, Emmert MY, Zund G, Baaijens FP, Hoerstrup SP (2010) Minimally-invasive implantation of living tissue engineered heart valves: a comprehensive approach from autologous vascular cells to stem cells. J Am Coll Cardiol 56(6):510–520. doi:10.1016/j.jacc.2010.04.024 PubMedGoogle Scholar
  9. 9.
    Ohyabu Y, Kida N, Kojima H, Taguchi T, Tanaka J, Uemura T (2006) Cartilaginous tissue formation from bone marrow cells using rotating wall vessel (RWV) bioreactor. Biotechnol Bioeng 95(5):1003–1008. doi:10.1002/bit.20892 PubMedGoogle Scholar
  10. 10.
    Tohyama H, Yasuda K, Minami A, Majima T, Iwasaki N, Muneta T, Sekiya I, Yagishita K, Takahashi S, Kurokouchi K, Uchio Y, Iwasa J, Deie M, Adachi N, Sugawara K, Ochi M (2009) Atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knee: a prospective multicenter clinical trial in Japan. J Orthop Sci 14(5):579–588. doi:10.1007/s00776-009-1384-1 PubMedGoogle Scholar
  11. 11.
    Haisch A (2010) Ear reconstruction through tissue engineering. Adv Otorhinolaryngol 68:108–119. doi:10.1159/000314566 PubMedGoogle Scholar
  12. 12.
    Ahmed TA, Giulivi A, Griffith M, Hincke M (2010) Fibrin glues in combination with mesenchymal stem cells to develop a tissue-engineered cartilage substitute. Tissue Eng A. doi:10.1089/ten.TEA.2009.0773 Google Scholar
  13. 13.
    L'Heureux N, Paquet S, Labbe R, Germain L, Auger FA (1998) A completely biological tissue-engineered human blood vessel. FASEB J 12(1):47–56PubMedGoogle Scholar
  14. 14.
    Isenberg BC, Williams C, Tranquillo RT (2006) Small-diameter artificial arteries engineered in vitro. Circ Res 98(1):25–35. doi:10.1161/01.RES.0000196867.12470.84 PubMedGoogle Scholar
  15. 15.
    Kerdjoudj H, Berthelemy N, Rinckenbach S, Kearney-Schwartz A, Montagne K, Schaaf P, Lacolley P, Stoltz JF, Voegel JC, Menu P (2008) Small vessel replacement by human umbilical arteries with polyelectrolyte film-treated arteries: in vivo behavior. J Am Coll Cardiol 52(19):1589–1597. doi:10.1016/j.jacc.2008.08.009 PubMedGoogle Scholar
  16. 16.
    Yang D, Guo T, Nie C, Morris SF (2009) Tissue-engineered blood vessel graft produced by self-derived cells and allogenic acellular matrix: a functional performance and histologic study. Ann Plast Surg 62(3):297–303. doi:10.1097/SAP.0b013e318197eb19 PubMedGoogle Scholar
  17. 17.
    Mirensky TL, Nelson GN, Brennan MP, Roh JD, Hibino N, Yi T, Shinoka T, Breuer CK (2009) Tissue-engineered arterial grafts: long-term results after implantation in a small animal model. J Pediatr Surg 44(6):1127–1132. doi:10.1016/j.jpedsurg.2009.02.035, discussion 1132–1123PubMedGoogle Scholar
  18. 18.
    Mirensky TL, Hibino N, Sawh-Martinez RF, Yi T, Villalona G, Shinoka T, Breuer CK (2010) Tissue-engineered vascular grafts: does cell seeding matter? J Pediatr Surg 45(6):1299–1305. doi:10.1016/j.jpedsurg.2010.02.102 PubMedGoogle Scholar
  19. 19.
    Roh JD, Sawh-Martinez R, Brennan MP, Jay SM, Devine L, Rao DA, Yi T, Mirensky TL, Nalbandian A, Udelsman B, Hibino N, Shinoka T, Saltzman WM, Snyder E, Kyriakides TR, Pober JS, Breuer CK (2010) Tissue-engineered vascular grafts transform into mature blood vessels via an inflammation-mediated process of vascular remodeling. Proc Natl Acad Sci USA 107(10):4669–4674. doi:10.1073/pnas.0911465107 PubMedGoogle Scholar
  20. 20.
    Enomoto S, Sumi M, Kajimoto K, Nakazawa Y, Takahashi R, Takabayashi C, Asakura T, Sata M (2010) Long-term patency of small-diameter vascular graft made from fibroin, a silk-based biodegradable material. J Vasc Surg 51(1):155–164. doi:10.1016/j.jvs.2009.09.005 PubMedGoogle Scholar
  21. 21.
    Koch S, Flanagan TC, Sachweh JS, Tanios F, Schnoering H, Deichmann T, Ella V, Kellomaki M, Gronloh N, Gries T, Tolba R, Schmitz-Rode T, Jockenhoevel S (2010) Fibrin-polylactide-based tissue-engineered vascular graft in the arterial circulation. Biomaterials 31(17):4731–4739. doi:10.1016/j.biomaterials.2010.02.051 PubMedGoogle Scholar
  22. 22.
    Neff LP, Tillman BW, Yazdani SK, Machingal MA, Yoo JJ, Soker S, Bernish BW, Geary RL, Christ GJ (2010) Vascular smooth muscle enhances functionality of tissue-engineered blood vessels in vivo. J Vasc Surg. doi:10.1016/j.jvs.2010.07.054 Google Scholar
  23. 23.
    Hibino N, McGillicuddy E, Matsumura G, Ichihara Y, Naito Y, Breuer C, Shinoka T (2010) Late-term results of tissue-engineered vascular grafts in humans. J Thorac Cardiovasc Surg 139(2):431–436. doi:10.1016/j.jtcvs.2009.09.057, 436 e431-432PubMedGoogle Scholar
  24. 24.
    Golinski PA, Zoller N, Kippenberger S, Menke H, Bereiter-Hahn J, Bernd A (2009) Development of an engraftable skin equivalent based on matriderm with human keratinocytes and fibroblasts. Handchir Mikrochir Plast Chir 41(6):327–332. doi:10.1055/s-0029-1234132 PubMedGoogle Scholar
  25. 25.
    Huang S, Xu Y, Wu C, Sha D, Fu X (2010) In vitro constitution and in vivo implantation of engineered skin constructs with sweat glands. Biomaterials 31(21):5520–5525. doi:10.1016/j.biomaterials.2010.03.060 PubMedGoogle Scholar
  26. 26.
    Yang J, Woo SL, Yang G, Wang J, Cui L, Liu W, Cao Y (2010) Construction and clinical application of a human tissue-engineered epidermal membrane. Plast Reconstr Surg 125(3):901–909. doi:10.1097/PRS.0b013e3181cc9665 PubMedGoogle Scholar
  27. 27.
    Ignatius A, Blessing H, Liedert A, Schmidt C, Neidlinger-Wilke C, Kaspar D, Friemert B, Claes L (2005) Tissue engineering of bone: effects of mechanical strain on osteoblastic cells in type I collagen matrices. Biomaterials 26(3):311–318. doi:10.1016/j.biomaterials.2004.02.045 PubMedGoogle Scholar
  28. 28.
    Janssen FW, van Dijkhuizen-Radersma R, Van Oorschot A, Oostra J, de Bruijn JD, Van Blitterswijk CA (2010) Human tissue-engineered bone produced in clinically relevant amounts using a semi-automated perfusion bioreactor system: a preliminary study. J Tissue Eng Regen Med 4(1):12–24. doi:10.1002/term.197 PubMedGoogle Scholar
  29. 29.
    Xu HH, Zhao L, Weir MD (2010) Stem cell-calcium phosphate constructs for bone engineering. J Dent Res 89(12):1482–1488. doi:10.1177/0022034510384623 PubMedGoogle Scholar
  30. 30.
    Garvin J, Qi J, Maloney M, Banes AJ (2003) Novel system for engineering bioartificial tendons and application of mechanical load. Tissue Eng 9(5):967–979. doi:10.1089/107632703322495619 PubMedGoogle Scholar
  31. 31.
    Nguyen TD, Liang R, Woo SL, Burton SD, Wu C, Almarza A, Sacks MS, Abramowitch S (2009) Effects of cell seeding and cyclic stretch on the fiber remodeling in an extracellular matrix-derived bioscaffold. Tissue Eng A 15(4):957–963. doi:10.1089/ten.tea.2007.0384 Google Scholar
  32. 32.
    Friedenstein AJ, Piatetzky S II, Petrakova KV (1966) Osteogenesis in transplants of bone marrow cells. J Embryol Exp Morphol 16(3):381–390PubMedGoogle Scholar
  33. 33.
    da Silva ML, Chagastelles PC, Nardi NB (2006) Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 119(Pt 11):2204–2213Google Scholar
  34. 34.
    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(5411):143–147PubMedGoogle Scholar
  35. 35.
    Dennis JE, Merriam A, Awadallah A, Yoo JU, Johnstone B, Caplan AI (1999) A quadripotential mesenchymal progenitor cell isolated from the marrow of an adult mouse. J Bone Miner Res 14(5):700–709PubMedGoogle Scholar
  36. 36.
    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(4):315–317PubMedGoogle Scholar
  37. 37.
    Choong PF, Mok PL, Cheong SK, Leong CF, Then KY (2007) Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy 9(2):170–183PubMedGoogle Scholar
  38. 38.
    Xu R, Jiang X, Guo Z, Chen J, Zou Y, Ke Y, Zhang S, Li Z, Cai Y, Du M, Qin L, Tang Y, Zeng Y (2008) Functional analysis of neuron-like cells differentiated from neural stem cells derived from bone marrow stroma cells in vitro. Cell Mol Neurobiol 28(4):545–558PubMedGoogle Scholar
  39. 39.
    Sun Y, Chen L, Hou XG, Hou WK, Dong JJ, Sun L, Tang KX, Wang B, Song J, Li H, Wang KX (2007) Differentiation of bone marrow-derived mesenchymal stem cells from diabetic patients into insulin-producing cells in vitro. Chin Med J (Engl) 120(9):771–776Google Scholar
  40. 40.
    Saulnier N, Lattanzi W, Puglisi MA, Pani G, Barba M, Piscaglia AC, Giachelia M, Alfieri S, Neri G, Gasbarrini G, Gasbarrini A (2009) Mesenchymal stromal cells multipotency and plasticity: induction toward the hepatic lineage. Eur Rev Med Pharmacol Sci 13(Suppl 1):71–78PubMedGoogle Scholar
  41. 41.
    Marcus AJ, Woodbury D (2008) Fetal stem cells from extra-embryonic tissues: do not discard. J Cell Mol Med 12(3):730–742PubMedGoogle Scholar
  42. 42.
    Pappa KI, Anagnou NP (2009) Novel sources of fetal stem cells: where do they fit on the developmental continuum? Regen Med 4(3):423–433PubMedGoogle Scholar
  43. 43.
    Can A, Karahuseyinoglu S (2007) Concise review: human umbilical cord stroma with regard to the source of fetus-derived stem cells. Stem Cells 25(11):2886–2895PubMedGoogle Scholar
  44. 44.
    Kita K, Gauglitz GG, Phan TT, Herndon DN, Jeschke MG (2009) Isolation and characterization of mesenchymal stem cells from the sub-amniotic human umbilical cord lining membrane. Stem Cells Dev 19(4):491–502Google Scholar
  45. 45.
    Covas DT, Siufi JL, Silva AR, Orellana MD (2003) Isolation and culture of umbilical vein mesenchymal stem cells. Braz J Med Biol Res 36(9):1179–1183PubMedGoogle Scholar
  46. 46.
    Panepucci RA, Siufi JL, Silva WA Jr, Proto-Siquiera R, Neder L, Orellana M, Rocha V, Covas DT, Zago MA (2004) Comparison of gene expression of umbilical cord vein and bone marrow-derived mesenchymal stem cells. Stem Cells 22(7):1263–1278PubMedGoogle Scholar
  47. 47.
    Sarugaser R, Lickorish D, Baksh D, Hosseini MM, Davies JE (2005) Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells 23(2):220–229PubMedGoogle Scholar
  48. 48.
    La Rocca G, Anzalone R, Corrao S, Magno F, Loria T, Lo Iacono M, Di Stefano A, Giannuzzi P, Marasa L, Cappello F, Zummo G, Farina F (2009) Isolation and characterization of Oct-4+/HLA-G + mesenchymal stem cells from human umbilical cord matrix: differentiation potential and detection of new markers. Histochem Cell Biol 131(2):267–282PubMedGoogle Scholar
  49. 49.
    Mitchell KE, Weiss ML, Mitchell BM, Martin P, Davis D, Morales L, Helwig B, Beerenstrauch M, Abou-Easa K, Hildreth T, Troyer D, Medicetty S (2003) Matrix cells from Wharton's jelly form neurons and glia. Stem Cells 21(1):50–60PubMedGoogle Scholar
  50. 50.
    Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D (2006) Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells 24(3):781–792PubMedGoogle Scholar
  51. 51.
    Karahuseyinoglu S, Cinar O, Kilic E, Kara F, Akay GG, Demiralp DO, Tukun A, Uckan D, Can A (2007) Biology of stem cells in human umbilical cord stroma: in situ and in vitro surveys. Stem Cells 25(2):319–331PubMedGoogle Scholar
  52. 52.
    Weiss ML, Troyer DL (2006) Stem cells in the umbilical cord. Stem Cell Rev 2(2):155–162PubMedGoogle Scholar
  53. 53.
    Troyer DL, Weiss ML (2008) Wharton's jelly-derived cells are a primitive stromal cell population. Stem Cells 26(3):591–599. doi:10.1634/stemcells.2007-0439 PubMedGoogle Scholar
  54. 54.
    Caplan AI (2009) Why are MSCs therapeutic? New data: new insight. J Pathol 217(2):318–324PubMedGoogle Scholar
  55. 55.
    Kuo CK, Li WJ, Mauck RL, Tuan RS (2006) Cartilage tissue engineering: its potential and uses. Curr Opin Rheumatol 18(1):64–73PubMedGoogle Scholar
  56. 56.
    Baksh D, Yao R, Tuan RS (2007) Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 25(6):1384–1392PubMedGoogle Scholar
  57. 57.
    Majore I, Moretti P, Hass R, Kasper C (2009) Identification of subpopulations in mesenchymal stem cell-like cultures from human umbilical cord. Cell Commun Signal 7:6PubMedGoogle Scholar
  58. 58.
    Hatlapatka T, Moretti P, Lavrentieva A, Hass R, Marquardt N, Roland J, Kasper C (2010) Optimization of culture conditions for the expansion of umbilical cord derived MSC like cells using xeno-free culture conditions. Tissue Eng Part C Methods. doi:10.1089/ten.TEC.2010.0406 Google Scholar
  59. 59.
    Hartmann I, Hollweck T, Haffner S, Krebs M, Meiser B, Reichart B, Eissner G (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(1):80–89. doi:10.1016/j.jim.2010.10.008 PubMedGoogle Scholar
  60. 60.
    Majore I, Moretti P, Stahl F, Hass R, Kasper C (2010) Growth and differentiation properties of mesenchymal stromal cell populations derived from whole human umbilical cord. Stem Cell Rev. doi:10.1007/s12015-010-9165-y Google Scholar
  61. 61.
    Vater C, Kasten P, Stiehler M (2010) Culture media for the differentiation of mesenchymal stromal cells. Acta Biomater. doi:10.1016/j.actbio.2010.07.037 PubMedGoogle Scholar
  62. 62.
    Kern S, Eichler H, Stoeve J, Kluter H, Bieback K (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24(5):1294–1301. doi:10.1634/stemcells.2005-0342 PubMedGoogle Scholar
  63. 63.
    Ronziere MC, Perrier E, Mallein-Gerin F, Freyria AM (2010) Chondrogenic potential of bone marrow- and adipose tissue-derived adult human mesenchymal stem cells. Biomed Mater Eng 20(3):145–158. doi:10.3233/BME-2010-0626 PubMedGoogle Scholar
  64. 64.
    Huang GT, Gronthos S, Shi S (2009) Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res 88(9):792–806. doi:10.1177/0022034509340867 PubMedGoogle Scholar
  65. 65.
    Stenderup K, Justesen J, Clausen C, Kassem M (2003) Aging is associated with decreased maximal life span and accelerated senescence of bone marrow stromal cells. Bone 33(6):919–926PubMedGoogle Scholar
  66. 66.
    Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13(12):4279–4295. doi:10.1091/mbc.E02-02-0105 PubMedGoogle Scholar
  67. 67.
    Puetzer JL, Petitte JN, Loboa EG (2010) Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue. Tissue Eng B Rev 16(4):435–444. doi:10.1089/ten.TEB.2009.0705 Google Scholar
  68. 68.
    Pelttari K, Steck E, Richter W (2008) The use of mesenchymal stem cells for chondrogenesis. Injury 39(Suppl 1):S58–S65. doi:10.1016/j.injury.2008.01.038 PubMedGoogle Scholar
  69. 69.
    Diekman BO, Rowland CR, Lennon DP, Caplan AI, Guilak F (2010) Chondrogenesis of adult stem cells from adipose tissue and bone marrow: induction by growth factors and cartilage-derived matrix. Tissue Eng A 16(2):523–533. doi:10.1089/ten.TEA.2009.0398 Google Scholar
  70. 70.
    Kuhbier JW, Weyand B, Radtke C, Vogt PM, Kasper C, Reimers K (2010) Isolation, characterization, differentiation, and application of adipose-derived stem cells. Adv Biochem Eng Biotechnol 123:55–105. doi:10.1007/10_2009_24 PubMedGoogle Scholar
  71. 71.
    Gomillion CT, Burg KJ (2006) Stem cells and adipose tissue engineering. Biomaterials 27(36):6052–6063. doi:10.1016/j.biomaterials.2006.07.033 PubMedGoogle Scholar
  72. 72.
    Hemmrich K, von Heimburg D, Cierpka K, Haydarlioglu S, Pallua N (2005) Optimization of the differentiation of human preadipocytes in vitro. Differentiation 73(1):28–35. doi:10.1111/j.1432-0436.2005.07301003.x PubMedGoogle Scholar
  73. 73.
    Jorgensen NR, Henriksen Z, Sorensen OH, Civitelli R (2004) Dexamethasone, BMP-2, and 1, 25-dihydroxyvitamin D enhance a more differentiated osteoblast phenotype: validation of an in vitro model for human bone marrow-derived primary osteoblasts. Steroids 69(4):219–226. doi:10.1016/j.steroids.2003.12.005 PubMedGoogle Scholar
  74. 74.
    Oh SH, Witek RP, Bae SH, Zheng D, Jung Y, Piscaglia AC, Petersen BE (2007) Bone marrow-derived hepatic oval cells differentiate into hepatocytes in 2-acetylaminofluorene/partial hepatectomy-induced liver regeneration. Gastroenterology 132(3):1077–1087. doi:10.1053/j.gastro.2007.01.001 PubMedGoogle Scholar
  75. 75.
    Sato Y, Araki H, Kato J, Nakamura K, Kawano Y, Kobune M, Sato T, Miyanishi K, Takayama T, Takahashi M, Takimoto R, Iyama S, Matsunaga T, Ohtani S, Matsuura A, Hamada H, Niitsu Y (2005) Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion. Blood 106(2):756–763. doi:10.1182/blood-2005-02-0572 PubMedGoogle Scholar
  76. 76.
    Song S, Zhang H, Cuevas J, Sanchez-Ramos J (2007) Comparison of neuron-like cells derived from bone marrow stem cells to those differentiated from adult brain neural stem cells. Stem Cells Dev 16(5):747–756. doi:10.1089/scd.2007.0027 PubMedGoogle Scholar
  77. 77.
    Tondreau T, Dejeneffe M, Meuleman N, Stamatopoulos B, Delforge A, Martiat P, Bron D, Lagneaux L (2008) Gene expression pattern of functional neuronal cells derived from human bone marrow mesenchymal stromal cells. BMC Genomics 9:166. doi:10.1186/1471-2164-9-166 PubMedGoogle Scholar
  78. 78.
    Wislet-Gendebien S, Wautier F, Leprince P, Rogister B (2005) Astrocytic and neuronal fate of mesenchymal stem cells expressing nestin. Brain Res Bull 68(1–2):95–102. doi:10.1016/j.brainresbull.2005.08.016 PubMedGoogle Scholar
  79. 79.
    Zhang HT, Fan J, Cai YQ, Zhao SJ, Xue S, Lin JH, Jiang XD, Xu RX (2010) Human Wharton's jelly cells can be induced to differentiate into growth factor-secreting oligodendrocyte progenitor-like cells. Differentiation 79(1):15–20. doi:10.1016/j.diff.2009.09.002 PubMedGoogle Scholar
  80. 80.
    Fu YS, Cheng YC, Lin MY, Cheng H, Chu PM, Chou SC, Shih YH, Ko MH, Sung MS (2006) Conversion of human umbilical cord mesenchymal stem cells in Wharton's jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 24(1):115–124. doi:10.1634/stemcells.2005-0053 PubMedGoogle Scholar
  81. 81.
    Moriscot C, de Fraipont F, Richard MJ, Marchand M, Savatier P, Bosco D, Favrot M, Benhamou PY (2005) Human bone marrow mesenchymal stem cells can express insulin and key transcription factors of the endocrine pancreas developmental pathway upon genetic and/or microenvironmental manipulation in vitro. Stem Cells 23(4):594–603. doi:10.1634/stemcells.2004-0123 PubMedGoogle Scholar
  82. 82.
    Tang DQ, Cao LZ, Burkhardt BR, Xia CQ, Litherland SA, Atkinson MA, Yang LJ (2004) In vivo and in vitro characterization of insulin-producing cells obtained from murine bone marrow. Diabetes 53(7):1721–1732PubMedGoogle Scholar
  83. 83.
    Krabbe C, Zimmer J, Meyer M (2005) Neural transdifferentiation of mesenchymal stem cells–a critical review. APMIS 113(11–12):831–844. doi:10.1111/j.1600-0463.2005.apm_3061.x PubMedGoogle Scholar
  84. 84.
    Wang HS, Hung SC, Peng ST, Huang CC, Wei HM, Guo YJ, Fu YS, Lai MC, Chen CC (2004) Mesenchymal stem cells in the Wharton's jelly of the human umbilical cord. Stem Cells 22(7):1330–1337. doi:10.1634/stemcells.2004-0013 PubMedGoogle Scholar
  85. 85.
    Martin-Rendon E, Sweeney D, Lu F, Girdlestone J, Navarrete C, Watt SM (2008) 5-Azacytidine-treated human mesenchymal stem/progenitor cells derived from umbilical cord, cord blood and bone marrow do not generate cardiomyocytes in vitro at high frequencies. Vox Sang 95(2):137–148. doi:10.1111/j.1423-0410.2008.01076.x PubMedGoogle Scholar
  86. 86.
    Glennie S, Soeiro I, Dyson PJ, Lam EW, Dazzi F (2005) Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells. Blood 105(7):2821–2827PubMedGoogle Scholar
  87. 87.
    Kode JA, Mukherjee S, Joglekar MV, Hardikar AA (2009) Mesenchymal stem cells: immunobiology and role in immunomodulation and tissue regeneration. Cytotherapy 11(4):377–391PubMedGoogle Scholar
  88. 88.
    Siegel G, Schafer R, Dazzi F (2009) The immunosuppressive properties of mesenchymal stem cells. Transplantation 87(9 Suppl):S45–S49PubMedGoogle Scholar
  89. 89.
    Le Blanc K, Rasmusson I, Sundberg B, Gotherstrom C, Hassan M, Uzunel M, Ringden O (2004) Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet 363(9419):1439–1441PubMedGoogle Scholar
  90. 90.
    Ringden O, Uzunel M, Rasmusson I, Remberger M, Sundberg B, Lonnies H, Marschall HU, Dlugosz A, Szakos A, Hassan Z, Omazic B, Aschan J, Barkholt L, Le Blanc K (2006) Mesenchymal stem cells for treatment of therapy-resistant graft-versus-host disease. Transplantation 81(10):1390–1397. doi:10.1097/01.tp.0000214462.63943.14 PubMedGoogle Scholar
  91. 91.
    Hui JH, Ouyang HW, Hutmacher DW, Goh JC, Lee EH (2005) Mesenchymal stem cells in musculoskeletal tissue engineering: a review of recent advances in National University of Singapore. Ann Acad Med Singapore 34(2):206–212PubMedGoogle Scholar
  92. 92.
    Kraus KH, Kirker-Head C (2006) Mesenchymal stem cells and bone regeneration. Vet Surg 35(3):232–242PubMedGoogle Scholar
  93. 93.
    Mobasheri A, Csaki C, Clutterbuck AL, Rahmanzadeh M, Shakibaei M (2009) Mesenchymal stem cells in connective tissue engineering and regenerative medicine: applications in cartilage repair and osteoarthritis therapy. Histol Histopathol 24(3):347–366PubMedGoogle Scholar
  94. 94.
    Sykova E, Jendelova P, Urdzikova L, Lesny P, Hejcl A (2006) Bone marrow stem cells and polymer hydrogels–two strategies for spinal cord injury repair. Cell Mol Neurobiol 26(7–8):1113–1129PubMedGoogle Scholar
  95. 95.
    Perin EC, Dohmann HF, Borojevic R, Silva SA, Sousa AL, Silva GV, Mesquita CT, Belem L, Vaughn WK, Rangel FO, Assad JA, Carvalho AC, Branco RV, Rossi MI, Dohmann HJ, Willerson JT (2004) Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 110(11 Suppl 1):II213–II218PubMedGoogle Scholar
  96. 96.
    Stamm C, Kleine HD, Westphal B, Petzsch M, Kittner C, Nienaber CA, Freund M, Steinhoff G (2004) CABG and bone marrow stem cell transplantation after myocardial infarction. Thorac Cardiovasc Surg 52(3):152–158PubMedGoogle Scholar
  97. 97.
    Fouillard L, Chapel A, Bories D, Bouchet S, Costa JM, Rouard H, Herve P, Gourmelon P, Thierry D, Lopez M, Gorin NC (2007) Infusion of allogeneic-related HLA mismatched mesenchymal stem cells for the treatment of incomplete engraftment following autologous haematopoietic stem cell transplantation. Leukemia 21(3):568–570PubMedGoogle Scholar
  98. 98.
    Lazarus HM, Koc ON, Devine SM, Curtin P, Maziarz RT, Holland HK, Shpall EJ, McCarthy P, Atkinson K, Cooper BW, Gerson SL, Laughlin MJ, Loberiza FR Jr, Moseley AB, Bacigalupo A (2005) Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant 11(5):389–398PubMedGoogle Scholar
  99. 99.
    Horwitz EM, Prockop DJ, Gordon PL, Koo WW, Fitzpatrick LA, Neel MD, McCarville ME, Orchard PJ, Pyeritz RE, Brenner MK (2001) Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood 97(5):1227–1231PubMedGoogle Scholar
  100. 100.
    Nakamura K, Ito Y, Kawano Y, Kurozumi K, Kobune M, Tsuda H, Bizen A, Honmou O, Niitsu Y, Hamada H (2004) Antitumor effect of genetically engineered mesenchymal stem cells in a rat glioma model. Gene Ther 11(14):1155–1164. doi:10.1038/sj.gt.3302276 PubMedGoogle Scholar
  101. 101.
    Nakamizo A, Marini F, Amano T, Khan A, Studeny M, Gumin J, Chen J, Hentschel S, Vecil G, Dembinski J, Andreeff M, Lang FF (2005) Human bone marrow-derived mesenchymal stem cells in the treatment of gliomas. Canc Res 65(8):3307–3318. doi:10.1158/0008-5472.CAN-04-1874 Google Scholar
  102. 102.
    Schichor C, Birnbaum T, Etminan N, Schnell O, Grau S, Miebach S, Aboody K, Padovan C, Straube A, Tonn JC, Goldbrunner R (2006) Vascular endothelial growth factor A contributes to glioma-induced migration of human marrow stromal cells (hMSC). Exp Neurol 199(2):301–310. doi:10.1016/j.expneurol.2005.11.027 PubMedGoogle Scholar
  103. 103.
    Birnbaum T, Roider J, Schankin CJ, Padovan CS, Schichor C, Goldbrunner R, Straube A (2007) Malignant gliomas actively recruit bone marrow stromal cells by secreting angiogenic cytokines. J Neurooncol 83(3):241–247. doi:10.1007/s11060-007-9332-4 PubMedGoogle Scholar
  104. 104.
    Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P (2007) MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109(9):4055–4063. doi:10.1182/blood-2006-10-051060 PubMedGoogle Scholar
  105. 105.
    Kim DS, Kim JH, Lee JK, Choi SJ, Kim JS, Jeun SS, Oh W, Yang YS, Chang JW (2009) Overexpression of CXC chemokine receptors is required for the superior glioma-tracking property of umbilical cord blood-derived mesenchymal stem cells. Stem Cells Dev 18(3):511–519. doi:10.1089/scd.2008.0050 PubMedGoogle Scholar
  106. 106.
    Caplan AI, Dennis JE (2006) Mesenchymal stem cells as trophic mediators. J Cell Biochem 98(5):1076–1084PubMedGoogle Scholar
  107. 107.
    Le Blanc K, Pittenger M (2005) Mesenchymal stem cells: progress toward promise. Cytotherapy 7(1):36–45PubMedGoogle Scholar
  108. 108.
    Majumdar MK, Thiede MA, Haynesworth SE, Bruder SP, Gerson SL (2000) Human marrow-derived mesenchymal stem cells (MSCs) express hematopoietic cytokines and support long-term hematopoiesis when differentiated toward stromal and osteogenic lineages. J Hematother Stem Cell Res 9(6):841–848PubMedGoogle Scholar
  109. 109.
    Meirelles Lda S, Fontes AM, Covas DT, Caplan AI (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20(5–6):419–427PubMedGoogle Scholar
  110. 110.
    Moretti P, Hatlapatka T, Marten D, Lavrentieva A, Majore I, Hass R, Kasper C (2010) Mesenchymal stromal cells derived from human umbilical cord tissues: primitive cells with potential for clinical and tissue engineering applications. Adv Biochem Eng Biotechnol 123:29–54. doi:10.1007/10_2009_15 PubMedGoogle Scholar
  111. 111.
    Parekkadan B, Milwid JM (2010) Mesenchymal stem cells as therapeutics. Annu Rev Biomed Eng 12:87–117. doi:10.1146/annurev-bioeng-070909-105309 PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Andres Hilfiker
    • 1
  • Cornelia Kasper
    • 2
  • Ralf Hass
    • 3
  • Axel Haverich
    • 1
    • 4
  1. 1.Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO)Hannover Medical SchoolHannoverGermany
  2. 2.Institut für Technische ChemieLeibniz Universität HannoverHannoverGermany
  3. 3.Laboratory of Biochemistry and Tumor Biology, Department of Obstetrics and GynecologyHannover Medical SchoolHannoverGermany
  4. 4.Department of Cardiac, Thoracic, Transplantation and Vascular SurgeryHannover Medical SchoolHannoverGermany

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