Endothelial Progenitor Cells Homing and Renal Repair in Experimental Renovascular Disease

被引:98
作者
Chade, Alejandro R. [1 ]
Zhu, Xiang-Yang [1 ]
Krier, James D. [1 ]
Jordan, Kyra L. [1 ]
Textor, Stephen C. [1 ]
Grande, Joseph P. [3 ]
Lerman, Amir [3 ]
Lerman, Lilach O. [1 ,2 ]
机构
[1] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA
[2] Mayo Clin, Div Cardiovasc Dis, Rochester, MN 55905 USA
[3] Mayo Clin, Div Lab Med & Pathol, Rochester, MN 55905 USA
关键词
Endothelial progenitor cells; Renal artery stenosis; Homing factors; EXPERIMENTAL HYPERCHOLESTEROLEMIA; HEMATOPOIETIC STEM; PERIPHERAL-BLOOD; STENOTIC KIDNEY; ARTERY STENOSIS; NEOVASCULARIZATION; ISCHEMIA; INJURY; ANGIOGENESIS; MOBILIZATION;
D O I
10.1002/stem.426
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Tissue injury triggers reparative processes that often involve endothelial progenitor cells (EPCs) recruitment. We hypothesized that atherosclerotic renal artery stenosis (ARAS) activates homing signals that would be detectable in both the kidney and EPCs, and attenuated on renal repair using selective cell-based therapy. Pigs were treated with intrarenal autologous EPC after 6 weeks of ARAS. Four weeks later, expression of homing-related signals in EPC and kidney, single kidney function, microvascular (MV) density, and morphology were compared with untreated ARAS and normal control pigs (n = 7 each). Compared with normal EPC, EPC from ARAS pigs showed increased stromal cell-derived factor (SDF)-1, angiopoietin-1, Tie-2, and c-kit expression, but downregulation of erythropoietin (EPO) and its receptor. The ARAS kidney released the c-kit-ligand stem cell factor, uric acid, and EPO, and upregulated integrin beta 2, suggesting activation of corresponding homing signaling. However, angiopoietin-1 and SDF-1/CXCR4 were not elevated. Administration of EPC into the stenotic kidney restored angiogenic activity, improved MV density, renal hemodynamics and function, decreased fibrosis and oxidative stress, and attenuated endogenous injury signals. The ARAS kidney releases specific homing signals corresponding to cognate receptors expressed by EPC. EPC show plasticity for organ-specific recruitment strategies, which are upregulated in early atherosclerosis. EPC are renoprotective as they attenuated renal dysfunction and damage in chronic ARAS, and consequently decreased the injury signals. Importantly, manipulation of homing signals may potentially allow therapeutic opportunities to increase endogenous EPC recruitment. STEM CELLS 2010;28:1039-1047
引用
收藏
页码:1039 / 1047
页数:9
相关论文
共 49 条
  • [1] Low-energy shock wave for enhancing recruitment of endothelial progenitor cells - A new modality to increase efficacy of cell therapy in chronic hind limb ischemia
    Aicher, Alexandra
    Heeschen, Christopher
    Sasaki, Ken-ichiro
    Urbich, Carmen
    Zeiher, Andreas M.
    Dimmeler, Stefanie
    [J]. CIRCULATION, 2006, 114 (25) : 2823 - 2830
  • [2] Differential healing activities of CD34+ and CD14+ endothelial cell progenitors
    Awad, O
    Dedkov, EI
    Jiao, CH
    Bloomer, S
    Tomanek, RJ
    Schatteman, GC
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (04) : 758 - 764
  • [3] Enhanced renal cortical vascularization in experimental hypercholesterolemia
    Bentley, MD
    Rodriguez-Porcel, M
    Lerman, A
    Sarafov, MH
    Romero, JC
    Pelaez, LI
    Grande, JP
    Ritman, EL
    Lerman, LO
    [J]. KIDNEY INTERNATIONAL, 2002, 61 (03) : 1056 - 1063
  • [4] Prevention of the ischemia-induced decrease in mitochondrial Tom20 content by ischemic preconditioning
    Boengler, Kerstin
    Gres, Petra
    Cabestrero, Alberto
    Ruiz-Meana, Marisol
    Garcia-Dorado, David
    Heusch, Gerd
    Schulz, Rainer
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2006, 41 (03) : 426 - 430
  • [5] Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis
    Brunner, Stefan
    Winogradow, Janina
    Huber, Bruno C.
    Zaruba, Marc-Michael
    Fischer, Rebekka
    David, Robert
    Assmann, Gerald
    Herbach, Nadja
    Wanke, Ruediger
    Mueller-Hoecker, Josef
    Franz, Wolfgang-Michael
    [J]. FASEB JOURNAL, 2009, 23 (02) : 351 - 361
  • [6] Simvastatin abates development of renal fibrosis in experimental renovascular disease
    Chade, Alejandro R.
    Zhu, Xiang Yang
    Grande, Joseph P.
    Krier, James D.
    Lerman, Amir
    Lerman, Lilach O.
    [J]. JOURNAL OF HYPERTENSION, 2008, 26 (08) : 1651 - 1660
  • [7] Simvastatin promotes angiogenesis and prevents microvascular remodeling in chronic renal ischemia
    Chade, Alejandro R.
    Zhu, Xiangyang
    Mushin, Oren P.
    Napoli, Claudio
    Lerman, Amir
    Lerman, Lilach O.
    [J]. FASEB JOURNAL, 2006, 20 (10) : 1706 - +
  • [8] Endothelial Progenitor Cells Restore Renal Function in Chronic Experimental Renovascular Disease
    Chade, Alejandro R.
    Zhu, Xiangyang
    Lavi, Ronit
    Krier, James D.
    Pislaru, Sorin
    Simari, Robert D.
    Napoli, Claudio
    Lerman, Amir
    Lerman, Lilach O.
    [J]. CIRCULATION, 2009, 119 (04) : 547 - U121
  • [9] Beneficial effects of antioxidant vitamins on the stenotic kidney
    Chade, AR
    Rodriguez-Porcel, M
    Herrmann, J
    Krier, JD
    Zhu, XY
    Lerman, A
    Lerman, LO
    [J]. HYPERTENSION, 2003, 42 (04) : 605 - 612
  • [10] Pathways of renal fibrosis and modulation of matrix turnover in experimental hypercholesterolemia
    Chade, AR
    Mushin, OP
    Zhu, XY
    Rodriguez-Porcel, M
    Grande, JP
    Textor, SC
    Lerman, A
    Lerman, LO
    [J]. HYPERTENSION, 2005, 46 (04) : 772 - 779