Skip to main content
SpringerLink
Log in

Bone marrow-derived stem cells and "plasticity"

  • Review Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Studies describing plasticity of somatic stem cells have become a focus of interest because clinical applications in the treatment of degenerative diseases would be at hand. In particular, bone marrow-derived cells and their potential to contribute to skeletal and cardiac muscle, liver, neurons and epithelium have recently been studied extensively. Nevertheless, results of these studies have not always been consistent with each other, and yet it remains to be resolved whether plasticity of adult stem cells truly exists. This review will discuss the role of bone marrow-derived stem cells in the field of experimental and clinical plasticity studies. Observations compatible with the concept of stem cell plasticity will be weighed against limitations of the experimental systems employed.

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.

Similar content being viewed by others

References

  1. Bianco P, Riminucci M, Gronthos S, Robey PG (2001) Bone marrow stromal stem cells: nature, biology, and potential applications. Stem Cells 19(3):180–192

    CAS  PubMed  Google Scholar 

  2. Bjornson CR, Rietze RL, Reynolds BA, Magli MC, Vescovi AL (1999) Turning brain into blood: a hematopoietic fate adopted by adult neural stem cells in vivo. Science 283(5401):534–537

    Google Scholar 

  3. Blau HM, Brazelton TR, Weimann JM (2001) The evolving concept of a stem cell: entity or function? Cell 105(7):829–841

    Google Scholar 

  4. Boyd AW, Schrader JW (1982) Derivation of macrophage-like lines from the pre-B lymphoma ABLS 8.1 using 5-azacytidine. Nature 297(5868):691–693

    CAS  PubMed  Google Scholar 

  5. Brazelton TR, Rossi FM, Keshet GI, Blau HM (2000) From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290(5497):1775–1779

    CAS  PubMed  Google Scholar 

  6. Bulfield G, Siller WG, Wight PA, Moore KJ (1984) X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci USA 81(4):1189–1192

    CAS  PubMed  Google Scholar 

  7. Castro RF, Jackson KA, Goodell MA, Robertson CS, Liu H, Shine HD (2003) Response to Comment on "Failure of Bone Marrow Cells to Transdifferentiate into Neural Cells in Vivo". Science 299(5610):1184

    Article  CAS  Google Scholar 

  8. Eglitis MA, Mezey E (1997) Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proc Natl Acad Sci USA 94(8):4080–4085

    Article  CAS  PubMed  Google Scholar 

  9. Ferrari G, Cusella-DeAngelis G, Coletta M, Paolucci E, Stornaiuolo A, Cossu G, Mavilio F (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279(5356):1528–1530

    Google Scholar 

  10. Ferrari G, Stornaiuolo A, Mavilio F (2001) Failure to correct murine muscular dystrophy. Nature 411(6841):1014–1015

    Article  CAS  PubMed  Google Scholar 

  11. Friedenstein AJ, Chailakhjan RK, Lalykina KS (1970) The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 3(4):393–403

    CAS  PubMed  Google Scholar 

  12. Friedenstein AJ, Petrakova KV, Kurolesova AI, Frolova GP (1968) Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation 6(2):230–247

    CAS  PubMed  Google Scholar 

  13. Geiger H, Sick S, Bonifer C, Müller AM (1998) Globin gene expression is reprogrammed in chimeras generated by injecting adult hematopoietic stem cells into mouse blastocysts. Cell 93(6):1055–1065

    CAS  PubMed  Google Scholar 

  14. Goodell MA, Brose K, Paradis G, Conner AS, Mulligan RC (1996) Isolation and functional properties of murine hematopoietic stem cells that are replicating in vivo. J Exp Med 183(4):1797–1806

    CAS  PubMed  Google Scholar 

  15. Graf T (2002) Differentiation plasticity of hematopoietic cells. Blood 99(9):3089–3101

    Article  CAS  PubMed  Google Scholar 

  16. Gussoni E, Soneoka Y, Strickland CD, Buzney EA, Khan MK, Flint AF, Kunkel LM, Mulligan RC (1999) Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401(6751):390–394

    Google Scholar 

  17. Ivanova NB, Dimos JT, Schaniel C, Hackney JA, Moore KA, Lemischka IR (2002) A stem cell molecular signature. Science 298(5593):601–604

    Article  CAS  PubMed  Google Scholar 

  18. Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, Entman ML, Michael LH, Hirschi KK, Goodell MA (2001) Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J Clin Invest 107(11):1395–1402

    CAS  PubMed  Google Scholar 

  19. Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM (2002) Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418(6893):41–49

    Article  CAS  PubMed  Google Scholar 

  20. Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S (2001) Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med 7(4):430–436

    PubMed  Google Scholar 

  21. Körbling M, Katz RL, Khanna A, Ruifrok AC, Rondon G, Albitar M, Champlin RE, Estrov Z (2002) Hepatocytes and epithelial cells of donor origin in recipients of peripheral-blood stem cells. N Engl J Med 346(10):738–746

    PubMed  Google Scholar 

  22. Krause DS, Theise ND, Collector MI, Henegariu O, Hwang S, Gardner R, Neutzel S, Sharkis SJ (2001) Multi-organ, multi-lineage engraftment by a single bone marrow-derived stem cell. Cell 105(3):369–377

    CAS  PubMed  Google Scholar 

  23. LaBarge MA, Blau HM (2002) Biological progression from adult bone marrow to mononucleate muscle stem cell to multinucleate muscle fiber in response to injury. Cell 111(4):589–601

    CAS  PubMed  Google Scholar 

  24. Laflamme MA, Myerson D, Saffitz JE, Murry CE (2002) Evidence for cardiomyocyte repopulation by extracardiac progenitors in transplanted human hearts. Circ Res 90(6):634–640

    Article  CAS  PubMed  Google Scholar 

  25. Lagasse E, Connors H, Al Dhalimy M, Reitsma M, Dohse M, Osborne L, Wang X, Finegold M, Weissman IL, Grompe M (2000) Purified hematopoietic stem cells can differentiate into hepatocytes in vivo. Nat Med 6(11):1229–1234

    Article  CAS  PubMed  Google Scholar 

  26. Mezey E, Key S, Vogelsang G, Szalayova I, Lange GD, Crain B (2003) Transplanted bone marrow generates new neurons in human brains. Proc Natl Acad Sci USA 100(3):1364–1369

    Article  CAS  PubMed  Google Scholar 

  27. Mezey E, Nagy A, Szalayova I, Key S, Bratincsak A, Baffi J, Shahar T (2003) Comment on "Failure of bone marrow cells to transdifferentiate into neural cells in vivo". Science 299(5610):1184

    Article  CAS  Google Scholar 

  28. Morshead CM, Benveniste P, Iscove NN, van der Kooy D (2002) Hematopoietic competence is a rare property of neural stem cells that may depend on genetic and epigenetic alterations. Nat Med 8(3):268–273

    Article  CAS  PubMed  Google Scholar 

  29. Müller P, Pfeiffer P, Koglin J, Schäfers HJ, Seeland U, Janzen I, Urbschat S, Böhm M (2002) Cardiomyocytes of noncardiac origin in myocardial biopsies of human transplanted hearts. Circulation 106(1):31–35

    Article  PubMed  Google Scholar 

  30. Neumann HA, Klinger Y (1994) Knochenmark und Stammzelle. Der Kampf um die Grundlagen der Hämatologie. Ex libris Roche 1. Blackwell Verlag, Berlin

  31. Orkin SH, Zon LI (2002) Hematopoiesis and stem cells: plasticity versus developmental heterogeneity. Nat Immunol 3(4):323–328

    Article  CAS  PubMed  Google Scholar 

  32. Orlic D, Arai AE, Sheikh FH, Agyeman KO, McGhee J, Hoyt RF, Sachdev V, Yu Z-X, San H, Metzger ME, Dunbar CE (2002) Cytokine mobilized CD34+ cells do not benefit rhesus monkeys following induced myocardial infarction (Abstract). Blood 100 (11): no 94

    Google Scholar 

  33. Orlic D, Cline A, Clevenger R, Sheikh FH, Chimenti S, Kajustra J, Dutra A, Pak E, Hoyt RF, Anversa P, Bodine DM (2002) Clonal Analysis of Mobilized Bone Marrow Stem Cell Regeneration of Acute Myocardial Infarctions in Mice (Abstract). Blood 100(11): no 1998

    Google Scholar 

  34. Orlic D, Kajstura J, Chimenti S, Jakoniuk I, Anderson SM, Li B, Pickel J, McKay R, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410(6829):701–705

    Google Scholar 

  35. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, Nadal-Ginard B, Bodine DM, Leri A, Anversa P (2001) Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 98(18):10344–10349

    CAS  PubMed  Google Scholar 

  36. Petersen BE, Bowen WC, Patrene KD, Mars WM, Sullivan AK, Murase N, Boggs SS, Greenberger JS, Goff JP (1999) Bone marrow as a potential source of hepatic oval cells. Science 284(5417):1168–1170

    Google Scholar 

  37. 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):143–147

    CAS  PubMed  Google Scholar 

  38. Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276(5309):71–74

    Google Scholar 

  39. Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2002) Chimerism of the transplanted heart. N Engl J Med 346(1):5–15

    PubMed  Google Scholar 

  40. Quesenberry PJ, Colvin GA, Lambert JF (2002) The chiaroscuro stem cell: a unified stem cell theory. Blood 100(13):4266–4271

    Article  CAS  PubMed  Google Scholar 

  41. Ramalho-Santos M, Yoon S, Matsuzaki Y, Mulligan RC, Melton DA (2002) "Stemness": transcriptional profiling of embryonic and adult stem cells. Science 298(5593):597–600

    Article  CAS  PubMed  Google Scholar 

  42. Reyes M, Lund T, Lenvik T, Aguiar D, Koodie L, Verfaillie CM (2001) Purification and ex vivo expansion of postnatal human marrow mesodermal progenitor cells. Blood 98(9):2615–2625

    CAS  PubMed  Google Scholar 

  43. Schwartz RE, Reyes M, Koodie L, Jiang Y, Blackstad M, Lund T, Lenvik T, Johnson S, Hu WS, Verfaillie CM (2002) Multipotent adult progenitor cells from bone marrow differentiate into functional hepatocyte-like cells. J Clin Invest 109(10):1291–1302

    PubMed  Google Scholar 

  44. Sharkis SJ, Cremo C, Collector MI, Noga SJ, Donnenberg AD (1986) Thymic regulation of hematopoiesis. III: isolation of helper and suppressor populations using counterflow centrifugal elutriation. Blood 68(3):787–789

    CAS  PubMed  Google Scholar 

  45. Stamm C, Westphal B, Kleine HD, Petzsch M, Kittner C, Klinge H, Schumichen C, Nienaber CA, Freund M, Steinhoff G (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361(9351):45–46

    Article  PubMed  Google Scholar 

  46. Strauer BE, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, Kögler G, Wernet P (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106(15):1913–1918

    Article  PubMed  Google Scholar 

  47. Terada N, Hamazaki T, Oka M, Hoki M, Mastalerz DM, Nakano Y, Meyer EM, Morel L, Petersen BE, Scott EW (2002) Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion. Nature 416(6880):542–545

    Google Scholar 

  48. Theise ND, Krause DS, Sharkis S (2003) Comment on "Little evidence for developmental plasticity of adult hematopoietic stem cells". Science 299(5611):1317

    Article  CAS  PubMed  Google Scholar 

  49. Theise ND, Nimmakayalu M, Gardner R, Illei PB, Morgan G, Teperman L, Henegariu O, Krause DS (2000) Liver from bone marrow in humans. Hepatology 32(1):11–16

    CAS  PubMed  Google Scholar 

  50. Thiele J, Varus E, Wickenhauser C, Kvasnicka HM, Metz K, Schaefer UW, Beelen DW (2002) Chimerism of cardiomyocytes and endothelial cells after allogeneic bone marrow transplantation in chronic myeloid leukemia. An autopsy study. Pathologe 23(6):405–410

    Article  CAS  PubMed  Google Scholar 

  51. Tse HF, Kwong YL, Chan JK, Lo G, Ho CL, Lau CP (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361(9351):47–49

    Article  PubMed  Google Scholar 

  52. Wagers AJ, Sherwood RI, Christensen JL, Weissman IL (2003) Response to Comment on "Little Evidence for Developmental Plasticity of Adult Hematopoietic Stem Cells". Science 299(5611):1317

    Article  CAS  PubMed  Google Scholar 

  53. Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M (2003) Cell fusion is the principal source of bone-marrow-derived hepatocytes. Nature 422(6934):897–901

    Google Scholar 

  54. Weimann JM, Charlton CA, Brazelton TR, Hackman RC, Blau HM (2003) Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains. Proc Natl Acad Sci USA 100(4):2088–2093

    Article  CAS  PubMed  Google Scholar 

  55. Ying QL, Nichols J, Evans EP, Smith AG (2002) Changing potency by spontaneous fusion. Nature 416(6880):545–548

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Hämatologie, Zentrum für Innere Medizin, Universitätsklinikum Essen, Hufelandstr. 55, 45147, Essen, Germany

    A. Hüttmann & U. Dührsen

  2. Institute of Zoology, Academia Sinica, 128 Academia Rd. Sec. 2, NanKang, 11529, Taipei, Taiwan, R.O.C.

    C. L. Li

Authors
  1. A. Hüttmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. L. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Dührsen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Hüttmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hüttmann, A., Li, C.L. & Dührsen, U. Bone marrow-derived stem cells and "plasticity". Ann Hematol 82, 599–604 (2003). https://doi.org/10.1007/s00277-003-0713-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-003-0713-2

Keywords

Search

Navigation