Skip to main content

Multipotent Stromal Cells (hMSCs)

  • Chapter
Human Adult Stem Cells

Part of the book series: Human Cell Culture ((HUCC,volume 7))

  • 864 Accesses

Abstract

The existence of the non-hematopoietic stem/progenitor cells from bone marrow known as mesenchymal stem cells, marrow stromal cells, or multipotent mesenchymal stromal cells (MSCs), was first suggested over a hundred years ago. Definitive evidence that bone marrow contains cells that can differentiate into fibroblasts as well as other mesenchymal cells has been available since the mid-1970s. Over the last three decades, a great deal of research has been conducted on MSCs in laboratories worldwide. It has been found that these cells are easily isolated from small volumes of bone marrow, can be expanded to large numbers in a relatively short period of time with basic tissue culture techniques and can undergo differentiation into several different tissue types. In addition, it has been shown that MSCs are a part of the body’s natural repair mechanism and, thus, there has been great interest in using MSCs for treatment of various diseases and injuries, such as diabetes, chronic heart failure, Parkinson’s disease, Alzheimer’s disease, and spinal cord injury, to name just a few. Although the knowledge of these cells has grown exponentially and interest in MSCs has increased proportionally, each lab has developed their own protocols and methods of isolation, culture and characterization, thus, making it difficult to compare the results from experiments with MSCs from different labs. In spite of the ease with which these cells are isolated and cultured, there are some important criteria for the culture of these cells which must be observed in order to produce MSCs which have the capability to expand, multidifferentiate, form colonies and also to perform well when used for in vitro and in~vivo studies and in clinical therapies. This chapter will cover human MSC isolation, expansion, characterization and potential therapeutic uses.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cohnheim J. (1867) Ueber Ebtzuendung and Eiterung. Arch. Path. Anat. Physiol. Klin. Med. 40: 1–79.

    Google Scholar 

  2. Friedenstein AJ, Gorskaja U, Kulagina NN. (1976) Fibroblast precursors in normal and irradiated mouse hematopoietic organs. Exp. Hematol. 4: 267–274.

    PubMed  CAS  Google Scholar 

  3. Prockop DJ, Sekiya I, Colter DC. (2001) Isolation and characterization of rapidly self-renewing stem cells from cultures of human marrow stromal cells. Cytotherapy 3:393–396.

    Article  PubMed  CAS  Google Scholar 

  4. Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, Cooper DR, Sanberg PR. (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp. Neurol. 164: 247–256.

    Article  PubMed  CAS  Google Scholar 

  5. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. (2000) Adult rat and human bone marrow stromal cells differentiate into neurons. J. Neurosci. Res. 61: 364–370.

    Article  PubMed  CAS  Google Scholar 

  6. Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, Fine A. (2001) Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development 128: 5181–5188.

    PubMed  CAS  Google Scholar 

  7. Wakitani S, Saito T, Caplan AI. (1995) Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve 18: 1417–1426.

    Article  PubMed  CAS  Google Scholar 

  8. Fukuda K. (2002) Molecular characterization of regenerated cardiomyocytes derived from adult mesenchymal stem cells. Congenit. Anom. Kyoto 42: 1–9.

    Article  PubMed  CAS  Google Scholar 

  9. Horwitz EM, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, Deans RJ, Krause DS, Keating A. (2005) Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 7: 393–395.

    Article  PubMed  CAS  Google Scholar 

  10. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E. (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8: 315–317.

    Article  PubMed  CAS  Google Scholar 

  11. Meyerrose TE, Roberts M, Ohlemiller KK, Vogler CA, Wirthlin L, Nolta JA, Sands MS. (2008) Lentiviral-transduced human mesenchymal stem cells persistently express therapeutic levels of enzyme in a xenotransplantation model of human disease. Stem Cells 26: 1713–1722.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang XY, La Russa VF, Reiser J. (2004) Transduction of bone-marrow-derived mesenchymal stem cells by using lentivirus vectors pseudotyped with modified RD114 envelope glycoproteins. J. Virol. 78(3):1219–1229.

    Article  PubMed  CAS  Google Scholar 

  13. Rubio D, Garcia-Castro J, Martin MC, de la FR, Cigudosa JC, Lloyd AC, Bernad A. (2005) Spontaneous human adult stem cell transformation. Cancer Res. 65: 3035–3039.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  15. Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, Lu M, Rosenblum M. (2000) Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 11(13): 3001–3005.

    Article  PubMed  CAS  Google Scholar 

  16. Olson L, Widenfalk J, Josephson A, Greitz D, Klason T, Kiyotani T, Lipson A, Ebendal T, Cao Y, Hofstetter C, Schwartz E, Prockop D, Manson S, Jubran M, Lindqvist E, Lundströmer K, Nosrta I, Nosrat C, Brené S, Spenger C. (2001) Experimental spinal cord injury models: protective and repair strategies. In: Tissue Engineering for Therapeutic Use 5. Y. Ikada and N. Ohshima, Eds. pp 21–36.

    Google Scholar 

  17. Zacharek A, Chen J, Cui X, Li A, Li Y, Roberts C, Feng Y, Gao Q, Chopp M. (2007) Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke. J. Cereb. Blood Flow Metab. 27(10): 1684–1691.

    Article  PubMed  CAS  Google Scholar 

  18. Schinköthe T, Bloch W, Schmidt A. (2008) In vitro secreting profile of human mesenchymal stem cells. Stem Cells Dev. 17(1): 199–206.

    Article  PubMed  CAS  Google Scholar 

  19. Penolazzi L, Lambertini E, Tavanti E, Torreggiani E, Vesce F, Gambari R, Piva R. (2008) Evaluation of chemokine and cytokine profiles in osteoblast progenitors from umbilical cord blood stem cells by BIO-PLEX technology. Cell Biol. Int. 32(2): 320–325.

    Article  PubMed  CAS  Google Scholar 

  20. Gerdoni E, Gallo B, Casazza S, Musio S, Bonanni I, Pedemonte E, Mantegazza R, Frassoni F, Mancardi G, Pedotti R, Uccelli A. (2007) Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann. Neurol. 61(3): 219–227.

    Article  PubMed  CAS  Google Scholar 

  21. Aggarwal S, Pittenger MF. (2005) Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 105(4): 1815–1822.

    Article  PubMed  CAS  Google Scholar 

  22. Le Blanc K, Ringdén O. (2007) Immunomodulation by mesenchymal stem cells and clinical experience. J. Intern. Med. 262(5): 509–525.

    Article  PubMed  CAS  Google Scholar 

  23. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts AI, Zhao RC, Shi Y. (2008) Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2(2):141–150.

    Article  PubMed  CAS  Google Scholar 

  24. Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, Phinney DG. (2007) Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc. Natl. Acad. Sci. USA. 104(26): 11002–11007.

    Article  PubMed  CAS  Google Scholar 

  25. Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. (2007) Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J. Immunol. 179(3): 1855–1863.

    PubMed  CAS  Google Scholar 

  26. Munoz JR, Stoutenger BR, Robinson AP, Spees JL, Prockop DJ. (2005) Human stem/progenitor cells from bone marrow promote neurogenesis of endogenous neural stem cells in the hippocampus of mice. Proc. Natl. Acad. Sci. USA. 102(50):18171–18176.

    Article  PubMed  CAS  Google Scholar 

  27. Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, Prockop DJ. (2006) Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc. Natl. Acad. Sci. USA. 103(46):17438–17443.

    Article  PubMed  CAS  Google Scholar 

  28. Spees JL, Olson SD, Ylostalo J, Lynch PJ, Smith J, Perry A, Peister A, Wang MY, Prockop DJ. (2003) Differentiation, cell fusion, and nuclear fusion during ex vivo repair of epithelium by human adult stem cells from bone marrow stroma. Proc. Natl. Acad. Sci. USA. 100(5): 2397–2402.

    Article  PubMed  CAS  Google Scholar 

  29. Spees JL, Olson SD, Whitney MJ, Prockop DJ. (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. USA. 103(5): 1283–1288.

    Article  PubMed  CAS  Google Scholar 

  30. Prockop DJ, Gregory CA, Spees JL. (2003) One strategy for cell and gene therapy: harnessing the power of adult stem cells to repair tissues. Proc. Natl. Acad. Sci. USA. 100 Suppl 1:11917–11923.

    Article  CAS  Google Scholar 

  31. Prockop DJ. (2007) “Stemness” does not explain the repair of many tissues by mesenchymal stem/multipotent stromal cells (MSCs). Clin. Pharmacol. Ther. September;82(3): 241–243.

    Article  CAS  Google Scholar 

  32. Caplan AI, Dennis JE. (2006) Mesenchymal stem cells as trophic mediators. J. Cell. Biochem. August 1;98(5): 1076–1084.

    Article  PubMed  CAS  Google Scholar 

  33. Wolfe M, Pochampally R, Swaney W, Reger RL. (2008) Isolation and culture of bone marrow-derived human multipotent stromal cells (hMSCs). Methods Mol. Biol. 449: 3–25.

    Article  PubMed  Google Scholar 

  34. Reger RL, Wolfe MR. (2008) Freezing harvested hMSCs and recovery of hMSCs from frozen vials for subsequent expansion, analysis, and experimentation. Methods Mol. Biol. 449:109–116.

    Article  PubMed  Google Scholar 

  35. DiGirolamo CM, Stokes D, Colter D, Phinney DG, Class R and Prockop DJ. (1999) Propagation and senescence of human marrow stromal cells in culture: a simple colony forming assay identifies samples with the greatest potential to propagate and differentiate. Br. J. Haematol. 107: 275–281.

    Article  PubMed  CAS  Google Scholar 

  36. Reger RL, Tucker AH, Wolfe MR. (2008) Differentiation and characterization of human MSCs. Methods Mol. Biol. 449: 93–107.

    Article  PubMed  CAS  Google Scholar 

  37. Baksh D, Song L, Tuan RS. (2004). Adult mesenchymal stem cells: characterization, differentiation, and application in cell and gene therapy. J. Cell. Mol. Med. 8(3): 301–316.

    Article  PubMed  CAS  Google Scholar 

  38. 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.

    Article  PubMed  CAS  Google Scholar 

  39. Bruder SP, Kurth AA, Shea M, Hayes WC, Jaiswal N, Kadiyala S. (1998). Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J. Orthop. Res. 16: 155–162.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  41. Sekiya I, Larson BL, Smith JR, Pochampally R, Cui JG, Prockop DJ. (2002) Expansion of human adult stem cells from bone marrow stroma: conditions that maximize the yields of early progenitors and evaluate their quality. Stem Cells 20: 530–541.

    Article  PubMed  Google Scholar 

  42. Sekiya I, Larson BL, Vuoristo JT, Reger RL, Prockop DJ. (2005) Comparison of effect of BMP-2, -4, and -6 on in vitro cartilage formation of human adult stem cells from bone marrow stroma. Cell Tissue Res. 320(2): 269–276.

    Article  PubMed  CAS  Google Scholar 

  43. Smith JR, Pochampally R, Perry A, Hsu S-C, Prockop DJ. (2004). Isolation of a highly clonogenic and multipotential subfraction of adult stem cells from bone marrow stroma. Stem Cells 22: 823–831.

    Article  PubMed  Google Scholar 

  44. Sekiya I, Colter DC, Prockop DJ. (2001) BMP-6 enhances chondrogenesis in a subpopulation of human marrow stromal cells. Biochem. Biophys. Res. Commun. 284: 411–418.

    Article  PubMed  CAS  Google Scholar 

  45. Eaves C, Glimm H, Eisterer W, Audet J, Maguer-Satta V, Piret J. (2001) Characterization of human hematopoietic cells with short-lived in vivo repopulating activity. Ann. NY Acad. Sci. 938: 63–70; discussion 70–71.

    Article  PubMed  CAS  Google Scholar 

  46. Ohtaki H, Ylostalo J, Foraker JE, Robinson AP, Reger RL, Shioda S, Prockop DJ. (2008). Stem/progenitor cells from bone marrow (hMSCs) decrease neural cell death in global ischemia by modulation of the inflammatory/immune responses. Proc. Natl. Acad. Sci. USA. 105(38): 14638–14643.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Margaret Wolfe .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Wolfe, M., Tucker, A., Reger, R.L., Prockop, D.J. (2009). Multipotent Stromal Cells (hMSCs). In: Masters, J.R., Palsson, B.Ø. (eds) Human Adult Stem Cells. Human Cell Culture, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-2269-1_2

Download citation

Publish with us

Policies and ethics