Therapeutic potential of endothelial progenitor cells in cardiovascular diseases

被引:192
作者
Dzau, VJ
Gnecchi, M
Pachori, AS
Morello, F
Melo, LG
机构
[1] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA
[2] Queens Univ, Dept Physiol, Kingston, ON K7L 3N6, Canada
关键词
coronary artery disease; endothelial progenitor cells; genetic engineering; myocardial infarction; neovascularization; vascular repair;
D O I
10.1161/01.HYP.0000168923.92885.f7
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Endothelial dysfunction and cell loss are prominent features in cardiovascular disease. Endothelial progenitor cells ( EPCs) originating from the bone marrow play a significant role in neovascularization of ischemic tissues and in re-endothelialization of injured blood vessels. Several studies have shown the therapeutic potential of EPC transplantation in rescue of tissue ischemia and in repair of blood vessels and bioengineering of prosthetic grafts. Recent small-scale trials have provided preliminary evidence of feasibility, safety, and efficacy in patients with myocardial and critical limb ischemia. However, several studies have shown that age and cardiovascular disease risk factors reduce the availability of circulating EPCs ( CEPCs) and impair their function to varying degrees. In addition, the relative scarcity of CEPCs limits the ability to expand these cells in sufficient numbers for some therapeutic applications. Priority must be given to the development of strategies to enhance the number and improve the function of CEPCs. Furthermore, alternative sources of EPC such as chord blood need to be explored. Strategies for improvement of cell adhesion, survival, and prevention of cell senescence are also essential to ensure therapeutic viability. Genetic engineering of EPCs may be a useful approach to developing these cells into efficient therapeutic tools. In the clinical arena there is pressing need to standardize the protocols for isolation, culture, and therapeutic application of EPC. Large-scale multi-center randomized trials are required to evaluate the long-term safety and efficacy of EPC therapy. Despite these hurdles, the outlook for EPC-based therapy for cardiovascular disease is promising.
引用
收藏
页码:7 / 18
页数:12
相关论文
共 122 条
[1]   Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells [J].
Aicher, A ;
Heeschen, C ;
Mildner-Rihm, C ;
Urbich, C ;
Ihling, C ;
Technau-Ihling, K ;
Zeiher, AM ;
Dimmeler, S .
NATURE MEDICINE, 2003, 9 (11) :1370-1376
[2]   Isolation of putative progenitor endothelial cells for angiogenesis [J].
Asahara, T ;
Murohara, T ;
Sullivan, A ;
Silver, M ;
vanderZee, R ;
Li, T ;
Witzenbichler, B ;
Schatteman, G ;
Isner, JM .
SCIENCE, 1997, 275 (5302) :964-967
[3]   Bone marrow origin of endothelial progenitor cells responsible for postnatal vasculogenesis in physiological and pathological neovascularization [J].
Asahara, T ;
Masuda, H ;
Takahashi, T ;
Kalka, C ;
Pastore, C ;
Silver, M ;
Kearne, M ;
Magner, M ;
Isner, JM .
CIRCULATION RESEARCH, 1999, 85 (03) :221-228
[4]   Effect of stromal-cell-derived factor 1 on stem-cell homing and tissue regeneration in ischaemic cardiomyopathy [J].
Askari, AT ;
Unzek, S ;
Popovic, ZB ;
Goldman, CK ;
Forudi, F ;
Kiedrowski, M ;
Rovner, A ;
Ellis, SG ;
Thomas, JD ;
DiCorleto, PE ;
Topol, EJ ;
Penn, MS .
LANCET, 2003, 362 (9385) :697-703
[5]   HMG-CoA reductase inhibitors reduce senescence and increase proliferation of endothelial progenitor cells via regulation of cell cycle regulatory genes [J].
Assmus, B ;
Urbich, C ;
Aicher, A ;
Hofmann, WK ;
Haendeler, J ;
Rössig, L ;
Spyridopoulos, I ;
Zeiher, AM ;
Dimmeler, S .
CIRCULATION RESEARCH, 2003, 92 (09) :1049-1055
[6]   Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction -: (TOPCARE-AMI) [J].
Assmus, B ;
Schächinger, V ;
Teupe, C ;
Britten, M ;
Lehmann, R ;
Döbert, N ;
Grünwald, F ;
Aicher, A ;
Urbich, C ;
Martin, H ;
Hoelzer, D ;
Dimmeler, S ;
Zeiher, AM .
CIRCULATION, 2002, 106 (24) :3009-3017
[7]   Adult cardiac stem cells are multipotent and support myocardial regeneration [J].
Beltrami, AP ;
Barlucchi, L ;
Torella, D ;
Baker, M ;
Limana, F ;
Chimenti, S ;
Kasahara, H ;
Rota, M ;
Musso, E ;
Urbanek, K ;
Leri, A ;
Kajstura, J ;
Nadal-Ginard, B ;
Anversa, P .
CELL, 2003, 114 (06) :763-776
[8]   Mechanisms of angioplasty and stent restenosis: implications for design of rational therapy [J].
Bennett, MR ;
O'Sullivan, M .
PHARMACOLOGY & THERAPEUTICS, 2001, 91 (02) :149-166
[9]   Administration of granulocyte colony-stimulating factor enhances endothelialization and microvessel formation in small-caliber synthetic vascular grafts [J].
Bhattacharya, V ;
Shi, Q ;
Ishida, A ;
Sauvage, LR ;
Hammond, WP ;
Wu, MHD .
JOURNAL OF VASCULAR SURGERY, 2000, 32 (01) :116-122
[10]   Isolation of endothelial cells and their progenitor cells from human peripheral blood [J].
Boyer, M ;
Townsend, LE ;
Vogel, LM ;
Falk, J ;
Reitz-Vick, D ;
Trevor, KT ;
Villalba, M ;
Bendick, PJ ;
Glover, JL .
JOURNAL OF VASCULAR SURGERY, 2000, 31 (01) :181-189