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The Role of Microenvironment Stromal Cells in Regenerative Medicine

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Regenerative Medicine
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Abstract

Regenerative medicine offers the potential for treatment and possibly cures debilitating diseases including heart disease, diabetes, Parkinson’s disease, and liver failure. Approaches using stem cells from various sources are in preclinical and clinical testing. The goal of these studies is to deliver cellular products capable of replacing damaged tissue and/or cells. However, the balance between cellular proliferation and differentiation is a carefully controlled process involving a range of growth factors and cytokines produced in large part by tissue stromal cells. These stromal cells make up the tissue microenvironment and appear to be essential for normal homeostasis. We hypothesize that tissue damage in many instances involves damage to the microenvironment resulting in a lack of signals through growth factor networks necessary to maintain survival and proliferation of tissue-specific stem cells and progenitor cells. Therefore, optimal repair of disease tissue must account for the damage to the stromal environment and will require reconstitution of the microenvironment to support the survival, proliferation, and differentiation of the tissue-specific stem cells or progenitor cells. Further, stromal cells from different tissues have distinct gene profiles and so a homologous source of stromal cells would minimize potential differences that could result in unwanted toxicities or biological effects.

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References

  1. Weiss L. The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec. 1976;186:161.

    Article  CAS  PubMed  Google Scholar 

  2. Lichtman MA. The ultrastructure of the hematopoietic microenvironment of the marrow: a review. Exp Hematol. 1981;9:391.

    CAS  PubMed  Google Scholar 

  3. Beltrami AP, Cessili D. Multipotent cells can be generated in vitro from several adult human organs (heart, liver, and bone marrow). Blood. 2007;110(9):3438–46.

    Article  CAS  PubMed  Google Scholar 

  4. Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cell. The International Society of Cellular Therapy position statement. Cytotherapy. 2006;8(4):315.

    Article  CAS  PubMed  Google Scholar 

  5. Bianco P, Riminucci M. The bone marrow stroma in vivo: ontogeny, structure, cellular composition and changes in disease. In: Beresford JN, Owens ME, editors. Marrow stromal cell culture. Handbooks in practical animal cell biology. Cambridge, UK: Cambridge University Press; 1998. p. 1025.

    Google Scholar 

  6. Dexter TM. Stromal cell associated haemopoiesis. J Cell Physiol Suppl. 1982;1:87.

    Article  CAS  PubMed  Google Scholar 

  7. Freidenstein AJ, Gorskaja JF, Kilagina NN. Fibroblast precursors in normal and irradiated hematopoietic organs. Exp Hematol. 1976;4(5):267–74.

    Google Scholar 

  8. Quirici N, Soligo D, Bossolasco P, et al. Isolation of bone marrow mesenchymal stem cells by anti-nerve growth factor receptor antibodies. Exp Hematol. 2002;30(7):783.

    Article  CAS  PubMed  Google Scholar 

  9. Jones E, English A, Kinsey SE, et al. Optimization of a flow cytometry-based protocol for detection and phenotypic characterization of multipotent mesenchymal stromal cells from human bone marrow. Cytometry B Clin Cytom. 2006;70:391–9.

    Article  PubMed  Google Scholar 

  10. Zannettino A, Paton S, Kortesidis A, et al. Human multipotential mesenchymal/stromal stem cell are derived from a discrete subpopulation of STRO-1bright/CD34-/CD45-/glycophorin-A- bone marrow cells. Haematogica. 2007;92(12):1707.

    Article  Google Scholar 

  11. Le Blanc K, Tammik C, Rosendahl K, et al. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003;31(10):890–6.

    Article  PubMed  Google Scholar 

  12. Klyushnenkova E, Shustova V, Mosca J, et al. Human mesenchymal stem cells induce unresponsiveness in preactivated but not naĂŻve alloantigen specific T cells. Exp Hematol. 1999;27: abstract 122.

    Google Scholar 

  13. Klyushnenkova E, Mosa JD, Zernetkina V, et al. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci. 2005;12(1):47–57.

    Article  CAS  PubMed  Google Scholar 

  14. Le Blanc K, Ringden O. Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005;11(5):321–34.

    Article  PubMed  Google Scholar 

  15. Le Blanc K, Rasmusson I, Gotherstrom C, et al. Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes. Scand J Immunol. 2004;60(3):307–15.

    Article  PubMed  Google Scholar 

  16. Bartholomew A, Sturgeon C, Siatskas M, et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol. 2002;30(1):42–8.

    Article  PubMed  Google Scholar 

  17. Lazarus HM, Koc ON, Devine SM, et al. Cotransplantation of HLA-identical sibling culture-expanded mesenchymal stem cells and hematopoietic stem cells in hematologic malignancy patients. Biol Blood Marrow Transplant. 2005;11(5):389–98.

    Article  PubMed  Google Scholar 

  18. Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815–22.

    Article  CAS  PubMed  Google Scholar 

  19. Lietchy KW, MacKenzie TC, Shaaban AF, et al. Human mesenchymal stem cells engraft and demonstrate site-specific differentiation after in utero transplantation in sheep. Nat Med. 2000;6(11):1282–6.

    Article  Google Scholar 

  20. Grinnemo KH, Mansson A, Dellgren G, et al. Xenoreactivity and engraftment of human mesenchymal stem cells transplanted into infracted rat myocardium. J Thorac Cardiovasc Surg. 2004;127(5):1293–300.

    Article  CAS  PubMed  Google Scholar 

  21. Arinzeh TL, Peter SL, Archambault MP, et al. Allogeneic mesenchymal stem cells regenerate bone in a critical-sized canine segmental defect. J Bone Joint Surg Am. 2003;85-A(10):1927–35.

    PubMed  Google Scholar 

  22. Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cells therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48(12):3464–74.

    Article  PubMed  Google Scholar 

  23. Mahmud N, Pang W, Cobbs C, et al. Studies on the route of administration and role of conditioning with radiation on unrelated allogeneic mismatched mesenchymal stem cell engraftment in a nonhuman primate model. Exp Hematol. 2004;32(5):494–501.

    Article  CAS  PubMed  Google Scholar 

  24. Haylock DN, Nilsson SK. Stem cell regulation by the hematopoietic stem cell niche. Cell Cycle. 2008;4(10):1353–5.

    Article  Google Scholar 

  25. Decker C, Greggs R, Duggan K, et al. Adhesive multiplicity in the interaction of embryonic fibroblasts and myoblasts with extracellular matrices. J Cell Biol. 1984;99:1398.

    Article  CAS  PubMed  Google Scholar 

  26. Choy M, Oltjen SL, Otani YS, et al. Fibroblast growth factor-2 stimulates embryonic cardiac mesenchymal cell proliferation. Dev Dyn. 1996;206:193.

    Article  CAS  PubMed  Google Scholar 

  27. Baudino TA, Carver W, Giles W, Borg TK. Cardiac fibroblasts: friend or foe? Am J Physiol Heart Circ Physiol. 2006;291:H1015.

    Article  CAS  PubMed  Google Scholar 

  28. Mazhari R, Hare JM. Mechanisms of action of mesenchymal stem cells in cardiac repair: potential influences on the cardiac stem cell niche. Nat Clin Pract Cardiovasc Med. 2007;4 suppl 1:S21–6.

    Article  PubMed  Google Scholar 

  29. Hatzistergos K, Quevedo H, Oskouei BN, et al. Bone marrow mesenchymal stem cells stimulate cardiac stem cell proliferation and differentiation. Circ Res. 2010;107:913–22.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Cordes KR, Srivastava D. MicroRNA regulation of cardiovascular development. Circ Res. 2009;104:724–32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Luzi E, Marini F, Sala SC, et al. Osteogenic differentiation of human adipose tissue-derived stem cells is modulated by the miR-26a targeting of the SMAD1 transcription factor. Bone Miner Res. 2008;23(2):287–95.

    Article  CAS  Google Scholar 

  32. Foshay KM, Gallicano GI. MiR-17 family miRNAs are expressed during early mammalian development and regulate stem cell differentiation. Dev Biol. 2009;326(2):431–43.

    Article  CAS  PubMed  Google Scholar 

  33. McCarthy JJ. MicroRNA-206: the skeletal muscle specific myomiR. Biochim Biophys Acta. 2008;1779:682–91.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Anderson C, Catoe H, Werner R. MIR-206 regulates connexin 43 expression during skeletal muscle development. Nucleic Acids Res. 2006;34(20):5863–71.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Shan ZX, Lin QX, Fu YH, et al. Upregulated expression of miR-1/miR-206 in a rat model of myocardial infarction. Biochem Biophys Res Commun. 2009;381:597–601.

    Article  CAS  PubMed  Google Scholar 

  36. Rossini A, Scopece A, Pompilio, et al. Cardiac stromal cells response to lineage-specific differentiation signals reveals commitment to a cardiovascular differentiation default program. Circulation. 2008;118:S280–1.

    Google Scholar 

  37. Adams BD, Cowee DM, White BA. The role of miR-206 in the epidermal growth factor (EGF) induced repression of estrogen receptor-alpha (ERalpha) signaling and luminal phenotype in MCF-7 breast cancer cells. Mol Endocrinol. 2009;23(8):1215–30.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Negrini M, Calin GA. Breast cancer metastasis: a microRNA story. Breast Cancer Res. 2008;10:303.

    Article  Google Scholar 

  39. Taulli R, Bersani F, Foglizzo, et al. The muscle-specific microRNA miR-206 blocks human rhabdomyosarcoma growth in xenotransplanted mice by promoting myogenic differentiation. J Clin Invest. 2009;119:2366–78.

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Kidd S, Spaeth E, Watson K, et al. Origins of the tumor microenvironment: quantitative assessment of adipose-derived and bone marrow-derived stroma. PLoS One. 2012;7(2):1–12.

    Google Scholar 

  41. Rossini A, Frati C, Lagrasta C, et al. Human cardiac and bone marrow stromal cells exhibit distinctive properties related to their origin. Cardiovasc Res. 2011;89(3):650–60.

    Article  CAS  PubMed  Google Scholar 

  42. Rossini A, Frati C, Lagrasta C, et al. Cardiac stromal-derived cells reveal higher proficiency to myocardial regeneration than bone marrow mesenchymal cells with identical genetic background. Circulation. 2009;120:S766.

    Google Scholar 

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Correspondence to Ian McNiece PhD .

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McNiece, I. (2015). The Role of Microenvironment Stromal Cells in Regenerative Medicine. In: Bhattacharya, N., Stubblefield, P. (eds) Regenerative Medicine. Springer, London. https://doi.org/10.1007/978-1-4471-6542-2_2

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  • DOI: https://doi.org/10.1007/978-1-4471-6542-2_2

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