Bone-marrow-derived cells for enhancing collateral development: mechanisms, animal data, and initial clinical experiences.
Initial animal studies of single angiogenic agents, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), generated enthusiasm for the concept that these agents might enhance collateral development and thereby provide alternative therapies for patients with vascular disease not amenable to traditional revascularization. The enthusiasm, apparently justified by the subsequent results of small nonrandomized phase-I clinical trials, was then tempered by the subsequent disappointing results of randomized clinical trials. In light of these disappointing results, investigators have pursued alternative strategies in an attempt to improve tissue perfusion. One such strategy is the utilization of bone marrow-derived cell therapy. This review discusses mechanistic pathways mediating the effects of such cell therapy, summarizes the animal and early clinical experience, and speculates on the potential of genetic manipulation of bone marrow-derived cells in an attempt to further enhance their potency.
Kinnaird
Tim
T
Cardiovascular Research Institute, MedStar Research Institute, Washington Hospital Center, Washington, DC, USA.
Stabile
Eugenio
E
Burnett
Mary Susan
MS
Epstein
Stephen E
SE
D000367:Age Factors; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D017321:Clinical Trials, Phase I as Topic; D003097:Collateral Circulation / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005544:Forecasting; D006133:Growth Substances / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007511:Ischemia / Q000503:physiopathology / Q000628:therapy*; D045164:Mesenchymal Stem Cell Transplantation; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D009203:Myocardial Infarction / Q000628:therapy; D017202:Myocardial Ischemia / Q000628:therapy; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000502:physiology; D019899:Paracrine Communication; D016032:Randomized Controlled Trials as Topic; D051381:Rats; D017154:Stromal Cells / Q000166:cytology / Q000637:transplantation
D006133:Growth Substances; D009569:Nitric Oxide