ABSTRACT
Results of studies of properties of adipose tissue stromal cells are summarized in this review. It contains data on separation and cultivation of these cells as well as description of their antigenic characteristics, ability to differentiate into cells of mesenchymal and nonmesenchymal origin, angiogenic potential, and potential for transfection and transfer of therapeutic genes. Analysis of perspectives of clinical use of adipose tissue stromal cells in therapy of cardiovascular and other diseases is also presented.
Subject(s)
Adipose Tissue/cytology , Ischemia/surgery , Multipotent Stem Cells/transplantation , Neovascularization, Physiologic , Stem Cell Transplantation/methods , Animals , Humans , Ischemia/pathology , Stromal Cells/cytologyABSTRACT
Much effort has been made in searching for multipotent cell types with high therapeutic potentials for repair of damaged tissue. Through enzymatic digestion of fat tissue, it is possible to obtain a large number of stromal cells. Isolated cells show a high proliferate capacity in culture. All this makes adipose stromal cells (ASC) promising candidates for their use in cell therapy. This review is focused on analyzing the surface antigen profile of isolated population of ASC, expression of angiogenic factors by these cells, as well as on their differentiation potential. A high percentage of ASC population initially express the progenitor cell marker CD34, but during culturing, cells exhibit a mesenchymal cell phenotype and express CD29, CD105, CD106, CD166. Culturing ASC in specific differentiation media induces expression of early markers of differentiated mesenchymal cells, such as adipocytes, chondrocytes and osteoblasts, as well as myoblasts, cardiomyocytes and neural cells. It has been also shown that ASC have a strong pro-angiogenic potential, they are able to secret growth factors, such as VEGF, HGF, bFGF and others, which stimulate survival and proliferation of endothelial cells. In addition, systemic or local delivery of ASC to mice with hindlimb ischemia stimulates recovery of injured tissue and blood flow. Potential clinical uses of ASCs are discussed in the review.
Subject(s)
Adipose Tissue/cytology , Stromal Cells/cytology , Adipocytes/cytology , Adipose Tissue/metabolism , Adipose Tissue/physiology , Animals , Antigens, CD/metabolism , Antigens, CD34/metabolism , Cell Adhesion Molecules, Neuronal/metabolism , Cell Differentiation , Cell Proliferation , Cell Transplantation , Cells, Cultured , Chondrocytes/cytology , Culture Media , Endoglin , Fetal Proteins/metabolism , Foot/blood supply , Foot/pathology , Growth Substances/metabolism , Humans , Integrin beta1/metabolism , Ischemia/pathology , Ischemia/therapy , Mice , Myoblasts/cytology , Myoblasts, Cardiac/cytology , Neurons/cytology , Osteoblasts/cytology , Receptors, Cell Surface/metabolism , Stromal Cells/metabolism , Stromal Cells/physiology , Vascular Cell Adhesion Molecule-1/metabolismABSTRACT
The review summarizes data obtained by the authors and other laboratories concerning the role of urokinase plasminogen activator in vessel remodeling and angiogenesis. The data have shown that urokinase is involved in unfavorable vascular remodeling during the development of restenosis, atherosclerosis and also in the regulation of angiogenesis. Urokinase is a promising target for therapeutic interventions aimed at restenosis prevention. Urokinase gene therapy may be a perspective strategy for the treatment of tissue ischemia.
