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
Weiss L. The hematopoietic microenvironment of the bone marrow: an ultrastructural study of the stroma in rats. Anat Rec. 1976;186:161.
Lichtman MA. The ultrastructure of the hematopoietic microenvironment of the marrow: a review. Exp Hematol. 1981;9:391.
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.
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.
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.
Dexter TM. Stromal cell associated haemopoiesis. J Cell Physiol Suppl. 1982;1:87.
Freidenstein AJ, Gorskaja JF, Kilagina NN. Fibroblast precursors in normal and irradiated hematopoietic organs. Exp Hematol. 1976;4(5):267–74.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815–22.
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.
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.
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.
Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cells therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48(12):3464–74.
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.
Haylock DN, Nilsson SK. Stem cell regulation by the hematopoietic stem cell niche. Cell Cycle. 2008;4(10):1353–5.
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.
Choy M, Oltjen SL, Otani YS, et al. Fibroblast growth factor-2 stimulates embryonic cardiac mesenchymal cell proliferation. Dev Dyn. 1996;206:193.
Baudino TA, Carver W, Giles W, Borg TK. Cardiac fibroblasts: friend or foe? Am J Physiol Heart Circ Physiol. 2006;291:H1015.
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.
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.
Cordes KR, Srivastava D. MicroRNA regulation of cardiovascular development. Circ Res. 2009;104:724–32.
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.
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.
McCarthy JJ. MicroRNA-206: the skeletal muscle specific myomiR. Biochim Biophys Acta. 2008;1779:682–91.
Anderson C, Catoe H, Werner R. MIR-206 regulates connexin 43 expression during skeletal muscle development. Nucleic Acids Res. 2006;34(20):5863–71.
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.
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.
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.
Negrini M, Calin GA. Breast cancer metastasis: a microRNA story. Breast Cancer Res. 2008;10:303.
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.
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.
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.
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.
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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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