| Stem cells offer the hope of curing a variety of ailments such as diabetes, Parkinson's disease, myocardial infarct, muscular dystrophy and spinal cord injuries. In this regard, a detailed understanding of the origin and behavior of stem cells is invaluable to the advancement of public health. The adult human adipose tissue (hWAT) is an attractive and convenient source of therapeutic cells for use in the clinical setting. Previous studies have demonstrated that the stromal vascular compartment within hWAT contains multipotent cells, called adipose stem cells (ASC). However, the identity and anatomic distribution of ASC or progenitors within hWAT remain unclear. We addressed this issue through an a priori identification of different cell subsets within the hWAT stroma, by visualization of cells in their native state within the resident tissue, and analysis of their immunohistochemical profile. Endothelial cells, pericytes, as well as non-vascular cells from adult subcutaneous abdominal fat were separated and sorted to homogeneity based on CD34, CD146 and CD45 antigen expression. We first tested the adipogenic potential of the different purified stromal cell populations. A higher level of leptin mRNA, as much as a 20-fold difference, was observed in pericytes and the non-vascular cell fractions when compared to endothelial cells. High levels of leptin expression were maintained even after extensive expansion of the cells in culture. Additionally, we found a reserve of brown adipocyte progenitors within the adult fat tissue vasculature, among pericytes, which challenges the notion that uncoupling protein-1 (UCP-1) expressing cells are confined to fetal and early human life. We also herein describe a precedently unsuspected role of adipose-derived pericytes as human muscle progenitors. When transplanted into cardiotoxin-injured NOD-SCID mouse muscles, pericytes generated a significantly higher number of myofibers than the other hWAT stromal cell populations. Quantitatively, the myogenic potential of adipose-derived pericytes was similar to that of a population of robustly myogenic cells within the skeletal muscle of adult humans, the "myogenic-endothelial cells". The long-term culture of hWAT pericytes did not diminish their capacity for myogenic differentiation. These results suggest that human adipose tissue is a viable alternative tissue source to skeletal muscle for muscle cell-mediated therapy. |
