Human Mesenchymal Stem Cells: Progenitor Cells for Cartilage, Bone, Fat and Stroma

  • M. F. Pittenger
  • J. D. Mosca
  • K. R. McIntosh
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 251)

Abstract

Bone marrow provides the rich milieu necessary to maintain myeloid and lymphoid progenitor cells throughout the life of an organism. At least two stem cell populations have been identified in marrow, the hematopoietic stem cell (HSC) and the mesenchymal stem cell (MSC). The HSC has been characterized in many ways, but much remains to be learned about its intrinsic potential and interactions with other cells of the marrow environment. We have studied the human stem cell population for mesenchymal tissues that resides in adult bone marrow. These MSCs potentially have the ability to differentiate to all mesenchymal cell types, including osteocytic, chondrocytic, adipocytic, myocytic, tenocytic, and also dermal and stromal lineages (1, 2). We have sought to understand the potential role(s) that MSCs play in healthy individuals and their response to trauma, disease or aging.

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References

  1. 1.
    Haynesworth SE, Goshima J, Goldberg VM, Caplan AI (1992) Characterization of cells with osteogenic potential from human bone marrow. Bone 13:81–88.PubMedCrossRefGoogle Scholar
  2. 2.
    Caplan, AI (1991) Mesenchymal stem cells. J. Orthop. Res. 9:641–650.PubMedCrossRefGoogle Scholar
  3. 3.
    Pittenger MF, Mackay AM, Beck S, Jaiswal R, Douglas R, Mosca J, Moorman MA, Simonetti D, Craig S, Marshak DR (1999) Multilineage potential of human mesenchymal stem cells. Science 284:143–147.PubMedCrossRefGoogle Scholar
  4. 4.
    Lazarus HM, Haynesworth SE, Gerson SL, Rosenthal NS, Caplan AI (1995) Ex vivo expansion and subsequent infusion of human bone marrow-derived stromal progenitor cells (mesenchymal progenitor cells): Implications for therapeutic use. Bone Marrow Transpl. 16:557–564Google Scholar
  5. 5.
    Urist, MR, McLean FC (1952) Osteogenic potency and new bone formation by induction in transplants to the anterior chamber of the eye. J. Bone Joint. Surgery Am. Vol. 34:443470.Google Scholar
  6. 6.
    Tavassoli M, Crosby W (1968) Transplant of marrow to extramedullary sites. Science 161:548–556.CrossRefGoogle Scholar
  7. 7.
    Friedenstein, AJ, Piatetzky-Shapiro, II, Petrokova, KV (1966) Osteogenesis in transplants of bone marrow cells. J. Embyrol. Exp. Morphol.16:381–390.Google Scholar
  8. 8.
    Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic transplants of bone marrow: Analysis of precursor cells for osteogenic and haematopoietic tissues. Transplantation 6:230–47.PubMedCrossRefGoogle Scholar
  9. 9.
    Friedenstein, AJ (1973) Determined and inducible osteogenic precursor cells. In: K. Elliott and D. Fitzsimmons (ed.$) Hard Tissue Growth, Repair and Remineralization. Ciba Found. Sympos.11:169–185.Google Scholar
  10. 10.
    Ashton BA, Allen TD, Howlett CR, Eaglesom CC, Hattori A, Owen M (1980) Formation of bone and cartilage by marrow stromal cells in diffusion chambers in vivo. Clin. Orth. Rel. Res. 151:294–307.Google Scholar
  11. 11.
    Friedenstein, AJ, Chailakhyan RK, Gerasimov UV (1987) Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet. 20:263–272.PubMedGoogle Scholar
  12. 12.
    Gregoriadis, AE, Heersche JNM, Aubin JE (1988) Differentiation of muscle, fat, cartilage, and bone from progenitor cells present in a bone derived clonal cell population: effect of dexamethasone. J. Cell Biology 106:2139–2151.CrossRefGoogle Scholar
  13. 13.
    Beresford JN, Bennett JH, Devlin C, LeBoy PS, Owen M (1992) Evidence for an inverse relationship between the differentiation of adipocytic and osteogenic cells in rat marrow stromal cell cultures. J. Cell Sci. 102:341–351.PubMedGoogle Scholar
  14. 14.
    Poliard A, Nifuji A, Lamblin D Forest C, Kellermann O (1995) Controlled conversion of an immortalized mesodermal progenitor cell towards osteogenic, chondrogenic and adipogenic pathways. J. Cell Biol. 130:1461–1472.PubMedCrossRefGoogle Scholar
  15. 15.
    Dennis JE, Merriam A, Awadalla A, Yoo RI, Johnstone B, Caplan AI (1999) A quadripotent mesenchymal progenitor cell isolated from the marrow of an adult mouse. J. Bone Miner. Res. 14:700–709.PubMedCrossRefGoogle Scholar
  16. 16.
    Pereira RF, Halford KW, O’Hara MD, Leeper DB, Sokolov BP, Pollard MD, Bagasra O, Prockop DJ (1995) Cultured adherent cells from marrow can serve as long-lasting precursor cells for bone, cartilage and lung in irradiated mice. Proc. Natl. Acad. Sci. USA. 92:48574861.Google Scholar
  17. 17.
    Dexter, TM, TD Allen, LG Lajtha (1977) Conditions controlling the proliferation of haematopoietic stem cells in vitro. J. Cell Physiology 91:335–344.CrossRefGoogle Scholar
  18. 18.
    Zipori, D, A Friedman, M Tamir, D. Silverberg, Z. Malik (1984) Cultured mouse marrow lines: interactions between fibroblastoid cells and monocytes. J. Cellular Physiol. 118:143152.Google Scholar
  19. 19.
    Dorshkind K (1990) Regulation of hemopoiesis by bone marrow stromal cells and their products. Ann. Rev. Immunol. 8:111–137.CrossRefGoogle Scholar
  20. 20.
    Pietrangeli, CE, Hayashi SI, Kincade PW (1988) Stromal cell lines which support lmphocyte growth: characterization, sensitivity to radiation and responsiveness to growth factors. Eur. J. Immunol. 18:863–872.PubMedCrossRefGoogle Scholar
  21. 21.
    Gimble, JM, Dorheim MA, Cheng Q, Medina K, Wang CS, Jones R, Koren E, Pietrangeli M, Kincade PW (1990) Adipogenesis in murine bone marrow stromal cell line capable of supporting B lineage lymphocyte growth and proliferation. Eur. J. Immunol. 20:379–387.PubMedCrossRefGoogle Scholar
  22. 22.
    Phinney DG, Kopen G, Isaacson RL, Prockop D (1999) Plastic adherent stromal cells from the bone marrow of commonly used strains of inbred mice: variations in yield, growth and differentiation. J. Cell. Biochem. 72:570–585.PubMedCrossRefGoogle Scholar
  23. 23.
    Lennon DP, Haynesworth SE, Bruder SP, Jaiswal N, Caplan, AI (1996) Development of a Serum Screen for Mesenchymal Progenitor Cells from Bone Marrow. In Vitro Animal Cellular & Developmental Biology 32: 602–611.Google Scholar
  24. 24.
    M.F. Pittenger, G. Mbalaviele, J. Mosca, M. Black, D.R. Marshal (2000) Adult Mesenchymal Stem Cells in Primary Mesenchymal Cells MR Koller, BO Palsson and JRW Masters, Editors. Dordrecht, Kluwer Academic Publishers. (In Press).Google Scholar
  25. 25.
    Barry FP, Johnstone B, Pittenger MF, Mackay AM, Murphy IM (1997) Modulation of the chondrogenic potential of human bone marrow-derived mesenchymal stem cells by TGFI3 1 and TGF03. Trans. Ortho Res. Soc. 22:228.Google Scholar
  26. 26.
    Mackay AM, Beck SC, Murphy JM, Barry FP, Chichester CO, Pittenger MF (1998) Chondrogenic differentiation of cultured human mesenchymal stem cells from marrow. Tissue Engin. 4:415–428.CrossRefGoogle Scholar
  27. 27.
    Yoo JU, Barthel TS, Nishimura K, Solchaga L, Caplan AI, Goldberg VM, Johnstone B (1998) The chondrogenic potential of human bone-marrow derived mesenchymal progenitor cells. J. Bone Joint Surg. 80A:1745–1757.Google Scholar
  28. 28.
    Jaiswal N, Haynesworth SE, Caplan AI, Bruder SP (1997) Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J. Cell. Biochem. 64: 295–312.PubMedCrossRefGoogle Scholar
  29. 29.
    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. Journal of Cellular Biochem. 64:278–294.CrossRefGoogle Scholar
  30. 30.
    Haynesworth SE, Baber MA, Caplan AI (1996) Cytokine expression by human marrow-derived mesenchymal progenitor cells in vitro: effects of dex and IL-la. J. Cell. Physiol. 166: 585–592.PubMedCrossRefGoogle Scholar
  31. 31.
    Allay JA, Dennis JE, Haynesworth SE, Majumdar MK, Clapp DW, Schultz LD, Caplan AI (1997) LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors. Hum Gene Therapy 8.1417–1427.CrossRefGoogle Scholar
  32. 32.
    Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL (1998) Phenotypic and functional comparison of marrow-derived mesenchymal stem cells and stromal cells. J. Cell. Phys. 176:57–66.CrossRefGoogle Scholar
  33. 33.
    Mbalaviele G, Lui L, Lee K, Novelli EM, Buyaner D, Deans R, Civin C, Mosca JD. Human mesenchymal stem cells can enhance human CD34+ cell repopulating NOD/SCID mice. Submitted for publication.Google Scholar
  34. 34.
    Barda-Saad M, Rozenszajn LA, Ashush H, Shav-Tal Y, Ben Nun A, Zipori D (1999) Adhesion molecules involved in the interactions between early T cells and mesenchymal bone marrow stromal cells. Exp. Hematol. 27:834–844.Google Scholar
  35. 35.
    Hojo H, Yaguchi M, Nagasu M, Aizawa S, Nakano M, Harigaya K, Handa H, Toyama K (1994) Establishment of a human thymic stromal cell line (R-3–4) and its adhesive capacity with T cells in vitro. Hematol. Pathol.8:177–185.Google Scholar
  36. 36.
    Fort MM, Pardoll DM (1996) Can bone marrow-derived thymic stromal cells mediate the positive selection of class I-restricted T cells? Cell. Immunol. 171:74–79.Google Scholar
  37. 37.
    Nonoyama S, Nakayama M, Abe J, Kohsaka T, Kobayashi N, Yata J (1992) Characterization of thymic lymphocytes forming rosettes with stromal cells. Tohoku J. Exp. Med. 168:467–474.Google Scholar
  38. 38.
    Owen JJ, Moore NC (1995) Thymic-stromal-cell interactions and T-cell selection. Immunol. Today 16:336–338.PubMedCrossRefGoogle Scholar
  39. 39.
    Mueller DL, Jenkins MK, Schwartz RH (1989) Clonal expansion versus functional clonal inactivation: A costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Ann. Rev. Immunol. 7:445–480.CrossRefGoogle Scholar
  40. 40.
    Cheng L, Qasba P, Padmavathy V, Thiede M (2000) Human mesenchymal stem cells support megakaryocyte and pro-platelet formation from CD34+ hematopoietic progenitor cells. J Cellular. Physiol. In press.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • M. F. Pittenger
    • 1
  • J. D. Mosca
    • 1
  • K. R. McIntosh
    • 1
  1. 1.Osiris Therapeutics, Inc.BaltimoreUSA

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