Skip to main content
SpringerLink
Log in

Bone marrow as a source of stem cells and germ cells? Perspectives for transplantation

  • Minireview
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Recent publications have suggested the existence of germ stem cells in the mouse at postnatal stages. The mechanism of de novo oocyte formation is proposed to involve a contribution from the bone marrow to the germ cell pool, via the bloodstream. Critical examination of the data underpinning these contentious claims is under way from a reproductive biology perspective but little has been said about the nature of this elusive bone marrow population with germ cell potential. Furthermore, whereas the prospect of marrow-derived germ cells may appear propitious for fertility applications, its wider impact on transplantation medicine remains to be considered. This paper examines the evidence leading to the current debate and considers the implications of such findings for the field of bone marrow transplantation.

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

  • Alvarez-Dolado M, Pardal R, Garcia-Verdugo JM, Fike JR, Lee HO, Pfeffer K, Lois C, Morrison SJ, Alvarez-Buylla A (2003) Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes. Nature 425:968–973

    Article  PubMed  CAS  Google Scholar 

  • Anjos-Afonso F, Siapati EK, Bonnet D (2004) In vivo contribution of murine mesenchymal stem cells into multiple cell-types under minimal damage conditions. J Cell Sci 117:5655–5664

    Article  PubMed  CAS  Google Scholar 

  • Baddoo M, Hill K, Wilkinson R, Gaupp D, Hughes C, Kopen GC, Phinney DG (2003) Characterization of mesenchymal stem cells isolated from murine bone marrow by negative selection. J Cell Biochem 89:1235–1249

    Article  PubMed  CAS  Google Scholar 

  • Bukovsky A (2005) Can ovarian infertility be treated with bone marrow- or ovary-derived germ cells? Reprod Biol Endocrinol 3:36

    Article  PubMed  Google Scholar 

  • Bukovsky A, Keenan JA, Caudle MR, Wimalasena J, Upadhyaya NB, Van Meter SE (1995) Immunohistochemical studies of the adult human ovary: possible contribution of immune and epithelial factors to folliculogenesis. Am J Reprod Immunol 33:323–340

    PubMed  CAS  Google Scholar 

  • Bukovsky A, Caudle MR, Svetlikova M, Upadhyaya NB (2004) Origin of germ cells and formation of new primary follicles in adult human ovaries. Reprod Biol Endocrinol 2:20

    Article  PubMed  Google Scholar 

  • Byskov AG, Faddy MJ, Lemmen JG, Andersen CY (2005) Eggs forever? Differentiation 73:438–446

    Article  PubMed  CAS  Google Scholar 

  • Couzin J (2004) Reproductive biology. Textbook rewrite? Adult mammals may produce eggs after all. Science 303:1593

    Article  PubMed  CAS  Google Scholar 

  • Daar AS, Sheremeta L (2003) The science of stem cells: ethical, legal and social issues. Exp Clin Transplant 1:139–146

    PubMed  Google Scholar 

  • Deng J, Petersen BE, Steindler DA, Jorgensen ML, Laywell ED (2006) Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24:1054–1064

    Article  PubMed  CAS  Google Scholar 

  • Dyce PW, Wen L, Li J (2006) In vitro germline potential of stem cells derived from fetal porcine skin. Nat Cell Biol 8:384–390

    Article  PubMed  CAS  Google Scholar 

  • Eggan K, Jurga S, Gosden R, Min IM, Wagers AJ (2006) Ovulated oocytes in adult mice derive from non-circulating germ cells. Nature 441:1109–1114

    Article  PubMed  CAS  Google Scholar 

  • Falciatori I, Borsellino G, Haliassos N, Boitani C, Corallini S, Battistini L, Bernardi G, Stefanini M, Vicini E (2004) Identification and enrichment of spermatogonial stem cells displaying side-population phenotype in immature mouse testis. FASEB J 18:376–378

    PubMed  CAS  Google Scholar 

  • 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 183:1797–1806

    Article  PubMed  CAS  Google Scholar 

  • Gosden RG (2004) Germline stem cells in the postnatal ovary: is the ovary more like a testis? Hum Reprod Update 10:193–195

    Article  PubMed  Google Scholar 

  • Gosden RG, Laing SC, Felicio LS, Nelson JF, Finch CE (1983) Imminent oocyte exhaustion and reduced follicular recruitment mark the transition to acyclicity in aging C57BL/6J mice. Biol Reprod 28:255–260

    Article  PubMed  CAS  Google Scholar 

  • Hermann A, Gastl R, Liebau S, Popa MO, Fiedler J, Boehm BO, Maisel M, Lerche H, Schwarz J, Brenner R, Storch A (2004) Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. J Cell Sci 117:4411–4422

    Article  PubMed  CAS  Google Scholar 

  • Hirschi KK, Goodell MA (2002) Hematopoietic, vascular and cardiac fates of bone marrow-derived stem cells. Gene Ther 9:648–652

    Article  PubMed  CAS  Google Scholar 

  • Hutt KJ, Albertini DF (2006) Clinical applications and limitations of current ovarian stem cell research: a review. J Exp Clin Assist Reprod 3:6

    Article  PubMed  Google Scholar 

  • Hutt KJ, McLaughlin EA, Holland MK (2006) KIT/KIT ligand in mammalian oogenesis and folliculogenesis: roles in rabbit and murine ovarian follicle activation and oocyte growth. Biol Reprod 75:421–433

    Article  PubMed  CAS  Google Scholar 

  • 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 418:41–49

    Article  PubMed  CAS  Google Scholar 

  • Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL (2004) Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature 428:145–150

    Article  PubMed  CAS  Google Scholar 

  • Johnson J, Bagley J, Skaznik-Wikiel M, Lee HJ, Adams GB, Niikura Y, Tschudy KS, Tilly JC, Cortes ML, Forkert R, Spitzer T, Iacomini J, Scadden DT, Tilly JL (2005) Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood. Cell 122:303–315

    Article  PubMed  CAS  Google Scholar 

  • Kayisli UA, Seli E (2006) Stem cells and fertility: what does the future hold? Curr Opin Obstet Gynecol 18:338–343

    Article  PubMed  Google Scholar 

  • Kerr JB, Duckett R, Myers M, Britt KL, Mladenovska T, Findlay JK (2006) Quantification of healthy follicles in the neonatal and adult mouse ovary: evidence for maintenance of primordial follicle supply. Reproduction 132:95–109

    Article  PubMed  CAS  Google Scholar 

  • Lassalle B, Bastos H, Louis JP, Riou L, Testart J, Dutrillaux B, Fouchet P, Allemand I (2004) “Side population” cells in adult mouse testis express Bcrp1 gene and are enriched in spermatogonia and germinal stem cells. Development 131:479–487

    Article  PubMed  CAS  Google Scholar 

  • Manova K, Nocka K, Besmer P, Bachvarova RF (1990) Gonadal expression of c-kit encoded at the W locus of the mouse. Development 110:1057–1069

    PubMed  CAS  Google Scholar 

  • McClellan KA, Gosden R, Taketo T (2003) Continuous loss of oocytes throughout meiotic prophase in the normal mouse ovary. Dev Biol 258:334–348

    Article  PubMed  CAS  Google Scholar 

  • McKinstry WJ, Li CL, Rasko JE, Nicola NA, Johnson GR, Metcalf D (1997) Cytokine receptor expression on hematopoietic stem and progenitor cells. Blood 89:65–71

    PubMed  CAS  Google Scholar 

  • McLaren A (2001) Ethical and social considerations of stem cell research. Nature 414:129–131

    Article  PubMed  CAS  Google Scholar 

  • McLaren A, Durcova-Hills G (2001) Germ cells and pluripotent stem cells in the mouse. Reprod Fertil Dev 13:661–664

    Article  PubMed  CAS  Google Scholar 

  • Meirelles Lda S, Nardi NB (2003) Murine marrow-derived mesenchymal stem cell: isolation, in vitro expansion, and characterization. Br J Haematol 123:702–711

    Article  PubMed  Google Scholar 

  • Morita Y, Ema H, Yamazaki S, Nakauchi H (2006) Non-side-population hematopoietic stem cells in mouse bone marrow. Blood 108:2850–2856

    Article  PubMed  CAS  Google Scholar 

  • Muguruma Y, Lee MY (1998) Isolation and characterization of murine clonogenic osteoclast progenitors by cell surface phenotype analysis. Blood 91:1272–1279

    PubMed  CAS  Google Scholar 

  • Nayernia K, Lee JH, Drusenheimer N, Nolte J, Wulf G, Dressel R, Gromoll J, Engel W (2006) Derivation of male germ cells from bone marrow stem cells. Lab Invest 86:654–663

    Article  PubMed  CAS  Google Scholar 

  • Okada S, Nakauchi H, Nagayoshi K, Nishikawa S, Nishikawa S, Miura Y, Suda T (1991) Enrichment and characterization of murine hematopoietic stem cells that express c-kit molecule. Blood 78:1706–1712

    PubMed  CAS  Google Scholar 

  • Okada S, Nakauchi H, Nagayoshi K, Nishikawa S, Miura Y, Suda T (1992) In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells. Blood 80:3044–3050

    PubMed  CAS  Google Scholar 

  • Oulad-Abdelghani M, Bouillet P, Decimo D, Gansmuller A, Heyberger S, Dolle P, Bronner S, Lutz Y, Chambon P (1996) Characterization of a premeiotic germ cell-specific cytoplasmic protein encoded by Stra8, a novel retinoic acid-responsive gene. J Cell Biol 135:469–477

    Article  PubMed  CAS  Google Scholar 

  • Palermo AT, Labarge MA, Doyonnas R, Pomerantz J, Blau HM (2005) Bone marrow contribution to skeletal muscle: a physiological response to stress. Dev Biol 279:336–344

    Article  PubMed  CAS  Google Scholar 

  • Pearce DJ, Ridler CM, Simpson C, Bonnet D (2004) Multiparameter analysis of murine bone marrow side population cells. Blood 103:2541–2546

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Powell K (2006) Born or made? Debate on mouse eggs reignites. Nature 441:795

    Article  PubMed  CAS  Google Scholar 

  • Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E, Marcacci M (2001) Repair of large bone defects with the use of autologous bone marrow stromal cells. N Engl J Med 344:385–386

    Article  PubMed  CAS  Google Scholar 

  • Rich IN (1995) Primordial germ cells are capable of producing cells of the hematopoietic system in vitro. Blood 86:463–472

    PubMed  CAS  Google Scholar 

  • Roufosse CA, Direkze NC, Otto WR, Wright NA (2004) Circulating mesenchymal stem cells. Int J Biochem Cell Biol 36:585–597

    Article  PubMed  CAS  Google Scholar 

  • Saitou M, Barton SC, Surani MA (2002) A molecular programme for the specification of germ cell fate in mice. Nature 418:293–300

    Article  PubMed  CAS  Google Scholar 

  • Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62

    Article  PubMed  CAS  Google Scholar 

  • Telfer EE, Gosden RG, Byskov AG, Spears N, Albertini D, Andersen CY, Anderson R, Braw-Tal R, Clarke H, Gougeon A, McLaughlin E, McLaren A, McNatty K, Schatten G, Silber S, Tsafriri A (2005) On regenerating the ovary and generating controversy. Cell 122:821–822

    Article  PubMed  CAS  Google Scholar 

  • Weimann JM, Johansson CB, Trejo A, Blau HM (2003) Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant. Nat Cell Biol 5:959–966

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Harada A, Bluethmann H, Wang JB, Nakao S, Mukaida N, Matsushima K (1995) Tumor necrosis factor (TNF) is a physiologic regulator of hematopoietic progenitor cells: increase of early hematopoietic progenitor cells in TNF receptor p55-deficient mice in vivo and potent inhibition of progenitor cell proliferation by TNF alpha in vitro. Blood 86:2930–2937

    PubMed  CAS  Google Scholar 

  • Zhang S, Jia Z, Ge J, Gong L, Ma Y, Li T, Guo J, Chen P, Hu Q, Zhang P, Liu Y, Li Z, Ma K, Li L, Zhou C (2005) Purified human bone marrow multipotent mesenchymal stem cells regenerate infarcted myocardium in experimental rats. Cell Transplant 14:787–798

    PubMed  Google Scholar 

Download references

Acknowledgements

My thanks to Dr. Helen Priddle and Dr. Rhodri Jones for helpful discussions and to Dr. Paul Scotting, Leigh Jackson and Prof. Jane Hewitt for critical reading of the manuscript.

Author information

Authors and Affiliations

  1. Institute of Genetics, Medical School, University of Nottingham, Nottingham, NG7 2UH, UK

    Virginie Sottile

Authors
  1. Virginie Sottile
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Virginie Sottile.

Additional information

The author is indebted to the Anne McLaren Fellowship Scheme of the University of Nottingham and to the Alzheimer’s Society for their support.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sottile, V. Bone marrow as a source of stem cells and germ cells? Perspectives for transplantation. Cell Tissue Res 328, 1–5 (2007). https://doi.org/10.1007/s00441-006-0361-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-006-0361-7

Keywords

Search

Navigation