Skip to main content
Log in

Mesenchymal stem cells hold promise for regenerative medicine

  • Review
  • Published:
Frontiers of Medicine Aims and scope Submit manuscript

Abstract

Regenerative medicine is an emerging interdisciplinary field of research that uses several technological approaches including stem cells to repair tissues. Mesenchymal stem cells (MSCs), a type of adult stem cell, have generated a great amount of interest over the past decade in this field. Numerous studies have explored the role of MSCs in tissue repair and modulation of allogeneic immune responses. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells as follows: the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial, and neuronal cells; the ability to secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting inflammation; the lack of immunogenicity; and the ability to perform immunomodulatory functions. In the present review, we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based. Furthermore, some pathological conditions under which the application of MSCs should be done with caution are also mentioned.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Greenwood HL, Singer PA, Downey GP, Martin DK, Thorsteinsdóttir H, Daar AS. Regenerative medicine and the developing world. PLoS Med 2006; 3(9): e381

    Article  PubMed  Google Scholar 

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

    CAS  Google Scholar 

  3. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8(4): 315–317

    Article  PubMed  CAS  Google Scholar 

  4. Zhao RC, Liao LM, Han Q. Mechanisms of and perspectives on the mesenchymal stem cell in immunotherapy. J Lab Clin Med 2004; 143(5): 284–291

    Article  PubMed  Google Scholar 

  5. Liechty KW, MacKenzie TC, Shaaban AF, Radu A, Moseley AM, Deans R, Marshak DR, Flake AW. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med 2000; 6(11): 1282–1286

    Article  PubMed  CAS  Google Scholar 

  6. Dan YY, Riehle KJ, Lazaro C, Teoh N, Haque J, Campbell JS, Fausto N. Isolation of multipotent progenitor cells from human fetal liver capable of differentiating into liver and mesenchymal lineages. Proc Natl Acad Sci USA 2006; 103(26): 9912–9917

    Article  PubMed  CAS  Google Scholar 

  7. Fang BJ, Shi MX, Liao LM, Yang S, Liu Y, Zhao RC. Multiorgan engraftment and multilineage differentiation by human fetal bone marrow Flk1+/CD31/CD34 progenitors. J Hematother Stem Cell Res 2003; 12(6): 603–613

    Article  PubMed  CAS  Google Scholar 

  8. Fang BJ, Liao LM, Shi MX, Yang S, Zhao RC. Multipotency of Flk1CD34 progenitors derived from human fetal bone marrow. J Lab Clin Med 2004; 143(4): 230–240

    Article  PubMed  CAS  Google Scholar 

  9. Guo H, Hu Y, Liao LM, Jiang XY, Liu JW, Ma L, Ma GJ, Zhao ZG, Yang SG, Zhao RC. Postembryonic subtotipotent stem cells derived from a variety of fetal tissues have multiple differentiation potential and greatly contribute to stem cell plasticity. China J Modern Med 2002; 12(16):1–9

    Google Scholar 

  10. Macias MI, Grande J, Moreno A, Domínguez I, Bornstein R, Flores AI. Isolation and characterization of true mesenchymal stem cells derived from human term decidua capable of multilineage differentiation into all 3 embryonic layers. Am J Obstet Gynecol 2010; 203(5):495.e9–495.e23

    Article  Google Scholar 

  11. Anzalone R, Lo Iacono M, Loria T, Di Stefano A, Giannuzzi P, Farina F, La Rocca G. Wharton’s jelly mesenchymal stem cells as candidates for beta cells regeneration: extending the differentiative and immunomodulatory benefits of adult mesenchymal stem cells for the treatment of type 1 diabetes. Stem Cell Rev 2011; 7(2): 342–363

    Article  PubMed  Google Scholar 

  12. De Coppi P, Bartsch G Jr, Siddiqui MM, Xu T, Santos CC, Perin L, Mostoslavsky G, Serre AC, Snyder EY, Yoo JJ, Furth ME, Soker S, Atala A. Isolation of amniotic stem cell lines with potential for therapy. Nat Biotechnol 2007; 25(1): 100–106

    Article  PubMed  Google Scholar 

  13. Battula VL, Bareiss PM, Treml S, Conrad S, Albert I, Hojak S, Abele H, Schewe B, Just L, Skutella T, Bühring HJ. Human placenta and bone marrow derived MSC cultured in serum-free, b-FGFcontaining medium express cell surface frizzled-9 and SSEA-4 and give rise to multilineage differentiation. Differentiation 2007; 75(4): 279–291

    Article  PubMed  CAS  Google Scholar 

  14. Miki T, Lehmann T, Cai H, Stolz DB, Strom SC. Stem cell characteristics of amniotic epithelial cells. Stem Cells 2005; 23(10): 1549–1559

    Article  PubMed  CAS  Google Scholar 

  15. Kögler G, Sensken S, Airey JA, Trapp T, Müschen M, Feldhahn N, Liedtke S, Sorg RV, Fischer J, Rosenbaum C, Greschat S, Knipper A, Bender J, Degistirici O, Gao J, Caplan AI, Colletti EJ, Almeida-Porada G, Müller HW, Zanjani E, Wernet P. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 2004; 200(2): 123–135

    Article  PubMed  Google Scholar 

  16. 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. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418(6893): 41–49

    Article  PubMed  CAS  Google Scholar 

  17. Li KH, Han Q, Yan X, Liao LM, Zhao RC. Not a process of simple vicariousness, the differentiation of human adipose-derived mesenchymal stem cells to renal tubular epithelial cells plays an important role in acute kidney injury repairing. Stem Cells Dev 2010; 19(8): 1267–1275

    Article  PubMed  CAS  Google Scholar 

  18. Yang Z, Li K, Yan X, Dong F, Zhao C. Amelioration of diabetic retinopathy by engrafted human adipose-derived mesenchymal stem cells in streptozotocin diabetic rats. Graefes Arch Clin Exp Ophthalmol 2010; 248(10): 1415–1422

    Article  PubMed  Google Scholar 

  19. Liu Y, Yan X, Sun Z, Chen B, Han Q, Li J, Zhao RC. Flk-1+ adipose-derived mesenchymal stem cells differentiate into skeletal muscle satellite cells and ameliorate muscular dystrophy in mdx mice. Stem Cells Dev 2007; 16(5): 695–706

    Article  PubMed  CAS  Google Scholar 

  20. Yan X, Liu Y, Han Q, Jia M, Liao L, Qi M, Zhao RC. Injured microenvironment directly guides the differentiation of engrafted Flk-1(+) mesenchymal stem cell in lung. Exp Hematol 2007; 35(9): 1466–1475

    Article  PubMed  CAS  Google Scholar 

  21. Cao Y, Sun Z, Liao L, Meng Y, Han Q, Zhao RC. Human adipose tissue-derived stem cells differentiate into endothelial cells in vitro and improve postnatal neovascularization in vivo. Biochem Biophys Res Commun 2005; 332(2): 370–379

    Article  PubMed  CAS  Google Scholar 

  22. Fang B, Shi M, Liao L, Yang S, Liu Y, Zhao RC. Systemic infusion of FLK1(+) mesenchymal stem cells ameliorate carbon tetrachloride-induced liver fibrosis in mice. Transplantation 2004;78(1):83–88

    Article  PubMed  CAS  Google Scholar 

  23. Deng W, Han Q, Liao L, Li C, Ge W, Zhao Z, You S, Deng H, Murad F, Zhao RC. Engrafted bone marrow-derived Flk-1+ mesenchymal stem cells regenerate skin tissue. Tissue Eng 2005; 11(1–2): 110–119

    Article  PubMed  CAS  Google Scholar 

  24. Bouffi C, Bony C, Courties G, Jorgensen C, Noël D. IL-6-dependent PGE2 secretion by mesenchymal stem cells inhibits local inflammation in experimental arthritis. PLoS ONE 2010; 5(12): e14247

    Article  PubMed  Google Scholar 

  25. Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med 2009; 15(1): 42–49

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  27. Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, Grisanti S, Gianni AM. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002; 99(10): 3838–3843

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  29. Selmani Z, Naji A, Zidi I, Favier B, Gaiffe E, Obert L, Borg C, Saas P, Tiberghien P, Rouas-Freiss N, Carosella ED, Deschaseaux F. Human leukocyte antigen-G5 secretion by human mesenchymal stem cells is required to suppress T lymphocyte and natural killer function and to induce CD4+CD25highFOXP3+ regulatory T cells. Stem Cells 2008; 26(1): 212–222

    Article  PubMed  CAS  Google Scholar 

  30. Uccelli A, Moretta L, Pistoia V. Mesenchymal stem cells in health and disease. Nat Rev Immunol 2008; 8(9): 726–736

    Article  PubMed  CAS  Google Scholar 

  31. Mei SH, Haitsma JJ, Dos Santos CC, Deng Y, Lai PF, Slutsky AS, Liles WC, Stewart DJ. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med 2010; 182(8): 1047–1057

    Article  PubMed  CAS  Google Scholar 

  32. Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells 2010; 28(12): 2229–2238

    Article  PubMed  CAS  Google Scholar 

  33. Kinnaird T, Stabile E, Burnett MS, Shou M, Lee CW, Barr S, Fuchs S, Epstein SE. Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms. Circulation 2004; 109(12): 1543–1549

    Article  PubMed  CAS  Google Scholar 

  34. Kinnaird T, Stabile E, Burnett MS, Lee CW, Barr S, Fuchs S, Epstein SE. Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res 2004; 94(5): 678–685

    Article  PubMed  CAS  Google Scholar 

  35. Li J, Zhu H, Liu Y, Li Q, Lu S, Feng M, Xu Y, Huang L, Ma C, An Y, Zhao RC, Wang R, Qin C. Human mesenchymal stem cell transplantation protects against cerebral ischemic injury and upregulates interleukin-10 expression in Macaca fascicularis. Brain Res 2010; 1334: 65–72

    Article  PubMed  CAS  Google Scholar 

  36. Lu S, Lu C, Han Q, Li J, Du Z, Liao L, Zhao RC. Adipose-derived mesenchymal stem cells protect PC12 cells from glutamate excitotoxicity-induced apoptosis by upregulation of XIAP through PI3-K/Akt activation. Toxicology 2011; 279(1–3): 189–195

    Article  PubMed  CAS  Google Scholar 

  37. Guo M, Sun Z, Sun QY, Han Q, Yu CL, Wang DH, Qiao JH, Chen B, Sun WJ, Hu KX, Liu GX, Liu B, Zhao RC, Ai H. A modified haploidentical nonmyeloablative transplantation without T cell depletion for high-risk acute leukemia: successful engraftment and mild GVHD. Biol Blood Marrow Transplant 2009; 15(8): 930–937

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  39. Bartholomew A, Sturgeon C, Siatskas M, Ferrer K, McIntosh K, Patil S, Hardy W, Devine S, Ucker D, Deans R, Moseley A, Hoffman R. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002; 30(1): 42–48

    Article  PubMed  Google Scholar 

  40. Shi D, Liao L, Zhang B, Liu R, Dou X, Li J, Zhu X, Yu L, Chen D, Zhao RC. Human adipose tissue-derived mesenchymal stem cells facilitate the immunosuppressive effect of cyclosporin A on T lymphocytes through Jagged-1-mediated inhibition of NF-κB signaling. Exp Hematol 2011; 39(2): 214–224, e1

    Article  PubMed  CAS  Google Scholar 

  41. Zhang W, Ge W, Li C, You S, Liao L, Han Q, Deng W, Zhao RC. Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells. Stem Cells Dev 2004; 13(3): 263–271

    Article  PubMed  CAS  Google Scholar 

  42. Chen L, Zhang W, Yue H, Han Q, Chen B, Shi M, Li J, Li B, You S, Shi Y, Zhao RC. Effects of human mesenchymal stem cells on the differentiation of dendritic cells from CD34+ cells. Stem Cells Dev 2007; 16(5): 719–732

    Article  PubMed  CAS  Google Scholar 

  43. Zhang B, Liu R, Shi D, Liu X, Chen Y, Dou X, Zhu X, Lu C, Liang W, Liao L, Zenke M, Zhao RC. Mesenchymal stem cells induce mature dendritic cells into a novel Jagged-2-dependent regulatory dendritic cell population. Blood 2009; 113(1): 46–57

    Article  PubMed  CAS  Google Scholar 

  44. Deng W, Han Q, Liao L, You S, Deng H, Zhao RC. Effects of allogeneic bone marrow-derived mesenchymal stem cells on T and B lymphocytes from BXSB mice. DNA Cell Biol 2005; 24(7): 458–463

    Article  PubMed  CAS  Google Scholar 

  45. Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, Vanbellinghen JF, Hafraoui K, Lejeune M, Gothot A, Fillet G, Beguin Y. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant 2010; 16(6): 838–847

    Article  PubMed  Google Scholar 

  46. Zhou H, Guo M, Bian C, Sun Z, Yang Z, Zeng Y, Ai H, Zhao RC. Efficacy of bone marrow-derived mesenchymal stem cells in the treatment of sclerodermatous chronic graft-versus-host disease: clinical report. Biol Blood Marrow Transplant 2010; 16(3): 403–412

    Article  PubMed  CAS  Google Scholar 

  47. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, Richardson AL, Polyak K, Tubo R, Weinberg RA. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 2007; 449(7162): 557–563

    Article  PubMed  CAS  Google Scholar 

  48. Chen B, Hu J, Liao L, Sun Z, Han Q, Song Z, Zhao RC. Flk-1+ mesenchymal stem cells aggravate collagen-induced arthritis by upregulating interleukin-6. Clin Exp Immunol 2010; 159(3): 292–302

    Article  PubMed  CAS  Google Scholar 

  49. Yang Z, Bian C, Zhou H, Huang S, Wang S, Liao L, Zhao RC. MicroRNA hsa-miR-138 inhibits adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells through adenovirus EID-1. Stem Cells Dev 2011; 20(2): 259–267

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert Chunhua Zhao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, S., Qu, X. & Zhao, R.C. Mesenchymal stem cells hold promise for regenerative medicine. Front. Med. 5, 372–378 (2011). https://doi.org/10.1007/s11684-011-0164-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11684-011-0164-4

Keywords

Navigation