Abstract：OBJECTIVE: Preclinical studies have demonstrated that exogenous mesenchymal stem cells (MSCs) may ameliorate kidney damage and enhance repair of renal ischemia reperfusion injury (IRI). This review will focus on the mechanism for accelerating repair of renal IRI by MSCs. Several chemokine receptors such as CXCR4 and CD44 are related to MSCs trafficking to post-ischemic kidney. MSCs differentiate into tubular epithelial cells, which is not the predominant mechanism for repair of the damaged kidney. Instead, MSCs exert their therapeutic effect mainly through paracrine action via a variety of cytokines and microvesicles, and the paracrine actions of infused MSCs work to activate intrinsic kidney cells, promote angiogenesis, inhibit oxidative stress and reduce apoptosis, inflammation and renal fibrosis.
TAO Yu-Hong,YE Li,WANG Ya-Mei et al. Mechanism for promoting repair of renal ischemia reperfusion injury by mesenchymal stem cells[J]. CJCP, 2013, 15(2): 157-160.
［11］Ponte AL, Marais E, Gallay N, Langonne A, Delorme B, Herault O, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities［J］. Stem Cells, 2007, 25(7): 1737-1745.
［1］Ali T, Khan I, Simpson W, Prescott G, Townend J, Smith W, et al. Incidence and outcomes in acute kidney injury: a comprehensive population-based study［J］. J Am Soc Nephrol, 2007, 18(4): 1292-1298.
［12］Fu X, Han B, Cai S, Lei Y, Sun T, Sheng Z. Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-alpha and its possible role in wound healing［J］. Wound Repair Regen, 2009, 17(2): 185-191.
［3］Togel F, Cohen A, Zhang P, Yang Y, Hu Z, Westenfelder C. Autologous and allogeneic marrow stromal cells are safe and effective for the treatment of acute kidney injury［J］. Stem Cells Dev, 2009, 18(3): 475-485.
［4］Duffield JS, Park KM, Hsiao LL, Kelley VR, Scadden DT, Ichimura T, et al. Restoration of tubular epithelial cells during repair of the postischemic kidney occurs independently of bone marrow-derived stem cells［J］. J Clin Invest, 2005, 115(7): 1743-1755.
［5］Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms［J］. Am J Physiol Renal Physiol, 2005, 289(1): F31-F42.
［6］Deak E, Seifried E, Henschler R. Homing pathways of mesenchymal stromal cells (MSCs) and their role in clinical applications［J］. Int Rev Immunol, 2010, 29(5): 514-529.
［7］Chen YT, Sun CK, Lin YC, Chang LT, Chen YL, Tsai TH, et al. Adipose-derived mesenchymal stem cell protects kidneys against ischemia-reperfusion injury through suppressing oxidative stress and inflammatory reaction［J］. J Transl Med, 2011, 9(1): 51-67.
［13］Schmidt A, Ladage D, Schinkothe T, Klausmann U, Ulrichs C, Klinz FJ, et al. Basic fibroblast growth factor controls migration in human mesenchymal stem cells［J］. Stem Cells, 2006, 24(7): 1750-1758.
［9］Bussolati B, Hauser PV, Carvalhosa R, Camussi G. Contribution of stem cells to kidney repair［J］. Curr Stem Cell Res Ther, 2009, 4(1): 2-8.
［14］Gao H, Priebe W, Glod J, Banerjee D. Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium［J］. Stem Cells, 2009, 27(4): 857-865.
［15］Togel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury［J］. Kidney Int, 2005, 67(5): 1772-1784.
［16］Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, et al. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo［J］. PLOS ONE, 2007, 3(5): e416-e427.
［10］Yagi H, Soto-Gutierrez A, Parekkadan B, Kitagawa Y, Tompkins RG, Kobayashi N, et al. Mesenchymal stem cells: Mechanisms of immunomodulation and homing［J］. Cell Transplant, 2010, 19(6): 667-679.
［17］Liu H, Liu S, Li Y, Wang X, Xue W, Ge G, et al. The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury［J］. PLOS ONE, 2012, 7(4): e34608-e34621.
［18］Goransson V, Johnsson C, Jacobson A, Heldin P, Hallgren R, Hansell P. Renal hyaluronan accumulation and hyaluronan synthase expression after ischaemia-reperfusion injury in the rat［J］. Nephrol Dial Transplant, 2004, 19(4): 823-830.
［11］Ponte AL, Marais E, Gallay N, Langonne A, Delorme B, Herault O, et al. The in vitro migration capacity of human bone marrow mesenchymal stem cells: comparison of chemokine and growth factor chemotactic activities［J］. Stem Cells, 2007, 25(7): 1737-1745.
［12］Fu X, Han B, Cai S, Lei Y, Sun T, Sheng Z. Migration of bone marrow-derived mesenchymal stem cells induced by tumor necrosis factor-alpha and its possible role in wound healing［J］. Wound Repair Regen, 2009, 17(2): 185-191.
［19］Zhu H, Mitsuhashi N, Klein A, Barsky LW, Weinberg K, Barr ML, et al. The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix［J］. Stem Cells, 2006, 24(4): 928-935.
［13］Schmidt A, Ladage D, Schinkothe T, Klausmann U, Ulrichs C, Klinz FJ, et al. Basic fibroblast growth factor controls migration in human mesenchymal stem cells［J］. Stem Cells, 2006, 24(7): 1750-1758.
［20］Herrera MB, Bussolati B, Bruno S, Morando L, Mauriello-Romanazzi G, Sanavio F, et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury［J］. Kidney Int, 2007, 72(4): 430-441.
［21］Tondreau T, Meuleman N, Stamatopoulos B, De Bruyn C, Delforge A, Dejeneffe M, et al. In vitro study of matrix metalloproteinase/tissue inhibitor of metalloproteinase production by mesenchymal stromal cells in response to inflammatory cytokines: the role of their migration in injured tissues［J］. Cytotherapy, 2009,11(5): 559-569.
［14］Gao H, Priebe W, Glod J, Banerjee D. Activation of signal transducers and activators of transcription 3 and focal adhesion kinase by stromal cell-derived factor 1 is required for migration of human mesenchymal stem cells in response to tumor cell-conditioned medium［J］. Stem Cells, 2009, 27(4): 857-865.
［22］Qian H, Yang H, Xu W, Yan Y, Chen Q, Zhu W, et al. Bone marrow mesenchymal stem cells ameliorate rat acute renal failure by differentiation into renal tubular epithelial-like cells［J］. Int J Mol Med, 2008, 22(3): 325-332.
［15］Togel F, Isaac J, Hu Z, Weiss K, Westenfelder C. Renal SDF-1 signals mobilization and homing of CXCR4-positive cells to the kidney after ischemic injury［J］. Kidney Int, 2005, 67(5): 1772-1784.
［23］Herrera MB, Bussolati B, Bruno S, Fonsato V, Romanazzi GM, Camussi G. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury［J］. Int J Mol Med, 2004,14(6): 1035-1041.
［16］Hung SC, Pochampally RR, Hsu SC, Sanchez C, Chen SC, Spees J, et al. Short-term exposure of multipotent stromal cells to low oxygen increases their expression of CX3CR1 and CXCR4 and their engraftment in vivo［J］. PLOS ONE, 2007, 3(5): e416-e427.
［17］Liu H, Liu S, Li Y, Wang X, Xue W, Ge G, et al. The role of SDF-1-CXCR4/CXCR7 axis in the therapeutic effects of hypoxia-preconditioned mesenchymal stem cells for renal ischemia/reperfusion injury［J］. PLOS ONE, 2012, 7(4): e34608-e34621.
［24］Kale S, Karihaloo A, Clark PR, Kashgarian M, Krause DS, Cantley LG. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule［J］. J Clin Invest, 2003, 112(1): 42-49.
［18］Goransson V, Johnsson C, Jacobson A, Heldin P, Hallgren R, Hansell P. Renal hyaluronan accumulation and hyaluronan synthase expression after ischaemia-reperfusion injury in the rat［J］. Nephrol Dial Transplant, 2004, 19(4): 823-830.
［25］Singaravelu K, Padanilam BJ. In vitro differentiation of MSC into cells with a renal tubular epithelial-like phenotype［J］. Ren Fail, 2009, 31(6): 492-502.
［27］Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation［J］. Arthritis Res Ther, 2007, 9(1): 204-214.
［28］Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T. Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation［J］. J Histochem Cytochem, 2005, 53(2): 207-216.
［19］Zhu H, Mitsuhashi N, Klein A, Barsky LW, Weinberg K, Barr ML, et al. The role of the hyaluronan receptor CD44 in mesenchymal stem cell migration in the extracellular matrix［J］. Stem Cells, 2006, 24(4): 928-935.
［32］Burst VR, Gillis M, Putsch F, Herzog R, Fischer JH, Heid P, et al. Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury［J］. Nephron Exp Nephrol, 2010,114(3): e107-e116.
［20］Herrera MB, Bussolati B, Bruno S, Morando L, Mauriello-Romanazzi G, Sanavio F, et al. Exogenous mesenchymal stem cells localize to the kidney by means of CD44 following acute tubular injury［J］. Kidney Int, 2007, 72(4): 430-441.
［33］Humphreys BD, Bonventre JV. Mesenchymal stem cells in acute kidney injury［J］. Annu Rev Med, 2008, 59(2): 311-325.
［21］Tondreau T, Meuleman N, Stamatopoulos B, De Bruyn C, Delforge A, Dejeneffe M, et al. In vitro study of matrix metalloproteinase/tissue inhibitor of metalloproteinase production by mesenchymal stromal cells in response to inflammatory cytokines: the role of their migration in injured tissues［J］. Cytotherapy, 2009,11(5): 559-569.
［34］Bi B, Schmitt R, Israilova M, Nishio H, Cantley LG. Stromal cells protect against acute tubular injury via an endocrine effect［J］. J Am Soc Nephrol, 2007, 18(9): 2486-2496.
［22］Qian H, Yang H, Xu W, Yan Y, Chen Q, Zhu W, et al. Bone marrow mesenchymal stem cells ameliorate rat acute renal failure by differentiation into renal tubular epithelial-like cells［J］. Int J Mol Med, 2008, 22(3): 325-332.
［23］Herrera MB, Bussolati B, Bruno S, Fonsato V, Romanazzi GM, Camussi G. Mesenchymal stem cells contribute to the renal repair of acute tubular epithelial injury［J］. Int J Mol Med, 2004,14(6): 1035-1041.
［24］Kale S, Karihaloo A, Clark PR, Kashgarian M, Krause DS, Cantley LG. Bone marrow stem cells contribute to repair of the ischemically injured renal tubule［J］. J Clin Invest, 2003, 112(1): 42-49.
［25］Singaravelu K, Padanilam BJ. In vitro differentiation of MSC into cells with a renal tubular epithelial-like phenotype［J］. Ren Fail, 2009, 31(6): 492-502.
［35］Togel F, Weiss K, Yang Y, Hu Z, Zhang P, Westenfelder C. Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury［J］. Am J Physiol Renal Physiol, 2007, 292(5): F1626-F1635.
［27］Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells. Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation［J］. Arthritis Res Ther, 2007, 9(1): 204-214.
［28］Oshima Y, Watanabe N, Matsuda K, Takai S, Kawata M, Kubo T. Behavior of transplanted bone marrow-derived GFP mesenchymal cells in osteochondral defect as a simulation of autologous transplantation［J］. J Histochem Cytochem, 2005, 53(2): 207-216.
［36］de Vries DK, Schaapherder AF, Reinders ME. Mesenchymal stromal cells in renal ischemia/reperfusion injury［J］. Front Immunol, 2012, 3(7): 162-170.
［32］Burst VR, Gillis M, Putsch F, Herzog R, Fischer JH, Heid P, et al. Poor cell survival limits the beneficial impact of mesenchymal stem cell transplantation on acute kidney injury［J］. Nephron Exp Nephrol, 2010,114(3): e107-e116.
［37］La Manna G, Bianchi F, Cappuccilli M, Cenacchi G, Tarantino L, Pasquinelli G, et al. Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model［J］. Cell Transplant, 2011, 20(8): 1193-1208.
［33］Humphreys BD, Bonventre JV. Mesenchymal stem cells in acute kidney injury［J］. Annu Rev Med, 2008, 59(2): 311-325.
［34］Bi B, Schmitt R, Israilova M, Nishio H, Cantley LG. Stromal cells protect against acute tubular injury via an endocrine effect［J］. J Am Soc Nephrol, 2007, 18(9): 2486-2496.
［35］Togel F, Weiss K, Yang Y, Hu Z, Zhang P, Westenfelder C. Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury［J］. Am J Physiol Renal Physiol, 2007, 292(5): F1626-F1635.
［36］de Vries DK, Schaapherder AF, Reinders ME. Mesenchymal stromal cells in renal ischemia/reperfusion injury［J］. Front Immunol, 2012, 3(7): 162-170.
［37］La Manna G, Bianchi F, Cappuccilli M, Cenacchi G, Tarantino L, Pasquinelli G, et al. Mesenchymal stem cells in renal function recovery after acute kidney injury: use of a differentiating agent in a rat model［J］. Cell Transplant, 2011, 20(8): 1193-1208.
［38］Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury［J］. Nephrol Dial Transplant, 2011, 26(5): 1474-1483.
［39］Camussi G, Deregibus MC, Tetta C. Paracrine/endocrine mechanism of stem cells on kidney repair: role of microvesicle-mediated transfer of genetic information［J］. Curr Opin Nephrol Hypertens, 2010, 19(1): 7-12.
［38］Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury［J］. Nephrol Dial Transplant, 2011, 26(5): 1474-1483.
［40］Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, et al. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs［J］. PLOS ONE, 2010, 5(7): e11803-e11818.
［41］Bruno S, Grange C, Deregibus MC, Calogero RA, Saviozzi S, Collino F, et al. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury［J］. J Am Soc Nephrol, 2009, 20(5): 1053-1067.
［39］Camussi G, Deregibus MC, Tetta C. Paracrine/endocrine mechanism of stem cells on kidney repair: role of microvesicle-mediated transfer of genetic information［J］. Curr Opin Nephrol Hypertens, 2010, 19(1): 7-12.
［42］Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury［J］. Nephrol Dial Transplant, 2011, 26(5): 1474-1483.
［43］Bruno S, Grange C, Collino F, Deregibus MC, Cantaluppi V, Biancone L, et al. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury［J］. PLOS ONE, 2012, 7(3): e33115e33126.
［40］Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, et al. Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs［J］. PLOS ONE, 2010, 5(7): e11803-e11818.
［45］Bussolati B, Collino F, Camussi G. CD133+ cells as a therapeutic target for kidney diseases［J］. Expert Opin Ther Targets, 2012, 16(2): 157-165.
［46］Huang Y, Chen P, Zhang CB, Ko GJ, Ruiz M, Fiorina P, et al. Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection［J］. Transplantation, 2010, 90(12): 1307-1311.
［47］Kitamura S, Yamasaki Y, Kinomura M, Sugaya T, Sugiyama H, Maeshima Y, et al. Establishment and characterization of renal progenitor like cells from S3 segment of nephron in rat adult kidney［J］. FASEB J, 2005,19(13): 789-1797.
［41］Bruno S, Grange C, Deregibus MC, Calogero RA, Saviozzi S, Collino F, et al. Mesenchymal stem cell-derived microvesicles protect against acute tubular injury［J］. J Am Soc Nephrol, 2009, 20(5): 1053-1067.
［42］Gatti S, Bruno S, Deregibus MC, Sordi A, Cantaluppi V, Tetta C, et al. Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury［J］. Nephrol Dial Transplant, 2011, 26(5): 1474-1483.
［43］Bruno S, Grange C, Collino F, Deregibus MC, Cantaluppi V, Biancone L, et al. Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury［J］. PLOS ONE, 2012, 7(3): e33115e33126.
［48］Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, et al. Intrinsic epithelial cells repair the kidney after injury［J］. Cell Stem Cell, 2008, 2(3): 284-291.
［45］Bussolati B, Collino F, Camussi G. CD133+ cells as a therapeutic target for kidney diseases［J］. Expert Opin Ther Targets, 2012, 16(2): 157-165.
［46］Huang Y, Chen P, Zhang CB, Ko GJ, Ruiz M, Fiorina P, et al. Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection［J］. Transplantation, 2010, 90(12): 1307-1311.
［49］Chen J, Park HC, Addabbo F, Ni J, Pelger E, Li H, et al. Kidney-derived mesenchymal stem cells contribute to vasculogenesis, angiogenesis and endothelial repair［J］. Kidney Int, 2008, 74(7): 879-889.
［47］Kitamura S, Yamasaki Y, Kinomura M, Sugaya T, Sugiyama H, Maeshima Y, et al. Establishment and characterization of renal progenitor like cells from S3 segment of nephron in rat adult kidney［J］. FASEB J, 2005,19(13): 789-1797.
［48］Humphreys BD, Valerius MT, Kobayashi A, Mugford JW, Soeung S, Duffield JS, et al. Intrinsic epithelial cells repair the kidney after injury［J］. Cell Stem Cell, 2008, 2(3): 284-291.
［51］Boomsma RA, Geenen DL. Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis［J］. PLOS ONE, 2012, 7(4): e35685-e35694.
［49］Chen J, Park HC, Addabbo F, Ni J, Pelger E, Li H, et al. Kidney-derived mesenchymal stem cells contribute to vasculogenesis, angiogenesis and endothelial repair［J］. Kidney Int, 2008, 74(7): 879-889.
［51］Boomsma RA, Geenen DL. Mesenchymal stem cells secrete multiple cytokines that promote angiogenesis and have contrasting effects on chemotaxis and apoptosis［J］. PLOS ONE, 2012, 7(4): e35685-e35694.
［52］Rivron NC, Vrij EJ, Rouwkema J, Le Gac S, van den Berg A, Truckenmüller RK, et al. Tissue deformation spatially modulates VEGF signaling and angiogenesis［J］. Proc Natl Acad Sci U S A, 2012,109(18): 6886-6891.
［53］van NAGP, Koolwijk P, Versteilen A, van HVW. Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro［J］. Arterioscler Thromb Vasc Biol, 2003, 23(2): 211-217.
［52］Rivron NC, Vrij EJ, Rouwkema J, Le Gac S, van den Berg A, Truckenmüller RK, et al. Tissue deformation spatially modulates VEGF signaling and angiogenesis［J］. Proc Natl Acad Sci U S A, 2012,109(18): 6886-6891.
［55］Zhuo W, Liao L, Xu T, Wu W, Yang S, Tan J. Mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal dysfunction by improving the antioxidant/oxidant balance in the ischemic kidney［J］. Urol Int, 2011, 86(2): 191-196.
［53］van NAGP, Koolwijk P, Versteilen A, van HVW. Involvement of RhoA/Rho kinase signaling in VEGF-induced endothelial cell migration and angiogenesis in vitro［J］. Arterioscler Thromb Vasc Biol, 2003, 23(2): 211-217.
［56］Wang Y, Hu F, Wang ZJ, Wang GX, Zhang ZH, Xie P, et al. Administration of bone marrow-derived stem cells suppresses cellular necrosis and apoptosis induced by reperfusion of ischaemic kidneys in rats［J］. Chin Med J (Engl), 2008, 121(3): 268-271.
［55］Zhuo W, Liao L, Xu T, Wu W, Yang S, Tan J. Mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal dysfunction by improving the antioxidant/oxidant balance in the ischemic kidney［J］. Urol Int, 2011, 86(2): 191-196.
［56］Wang Y, Hu F, Wang ZJ, Wang GX, Zhang ZH, Xie P, et al. Administration of bone marrow-derived stem cells suppresses cellular necrosis and apoptosis induced by reperfusion of ischaemic kidneys in rats［J］. Chin Med J (Engl), 2008, 121(3): 268-271.
［58］Imberti B, Morigi M, Tomasoni S, Rota C, Corna D, Longaretti L, et al. Insulin-like growth factor-1 sustains stem cell mediated renal repair［J］. J Am Soc Nephrol, 2007, 18(11): 2921-2928.
［59］Hara Y, Stolk M, Ringe J, Dehne T, Ladhoff J, Kotsch K, et al. In vivo effect of bone marrow-derived mesenchymal stem cells in a rat kidney transplantation model with prolonged cold ischemia［J］. Transpl Int, 2011, 24(11): 1112-1123.
［58］Imberti B, Morigi M, Tomasoni S, Rota C, Corna D, Longaretti L, et al. Insulin-like growth factor-1 sustains stem cell mediated renal repair［J］. J Am Soc Nephrol, 2007, 18(11): 2921-2928.
［59］Hara Y, Stolk M, Ringe J, Dehne T, Ladhoff J, Kotsch K, et al. In vivo effect of bone marrow-derived mesenchymal stem cells in a rat kidney transplantation model with prolonged cold ischemia［J］. Transpl Int, 2011, 24(11): 1112-1123.
［60］Semedo P, Correa-Costa M, Antonio CM, Maria ACMD, Antonia dRM, Shimizu MH, et al. Mesenchymal stem cells attenuate renal fibrosis through immune modulation and remodeling properties in a rat remnant kidney model［J］. Stem Cells, 2009, 27(12): 3063-3073.
［60］Semedo P, Correa-Costa M, Antonio CM, Maria ACMD, Antonia dRM, Shimizu MH, et al. Mesenchymal stem cells attenuate renal fibrosis through immune modulation and remodeling properties in a rat remnant kidney model［J］. Stem Cells, 2009, 27(12): 3063-3073.
