Characterization of Mesenchymal Progenitor Cell Populations Directly Derived from Human Dermis

Abstract

Mesenchymal stem cell (MSC) and progenitor cell (MPC) populations in human dermis remain poorly characterized, despite their importance to wound repair and the pathogenesis of many skin diseases. To identify MSC/MPC populations in human dermis we developed an 11-marker flow cytometry technique that enabled sorting of mesenchymal cell populations for functional assays, using adipose-derived stem cells (ASCs) from human adipose tissue as a positive control. Two populations of dermal cells had similar phenotypes to ASCs: both were CD34⁺ CD73⁺ CD105⁻/low, and lacked expression of c-kit (CD117) and hematopoietic or vascular markers (CD31, CD45, CD146, and HLA-DR). However, whereas ASCs were CD36^+/− CD90⁺, dermal mesenchymal progenitor cells (DMPCs) were split between a dominant CD36⁻ CD90⁺ population (DMPC1) and a small CD36⁺ CD90⁻ population (DMPC2). Both these populations were capable of differentiating into adipocytes, but only DMPC1 localized to a perivascular location, similar to that reported for ASCs. Re-gating of the flow cytometry data revealed that both DMPC1 and DMPC2 were part of CD45⁻ CD73⁺ CD146⁻ populations with variable expression of CD34. This suggests that CD34 may not be a stable marker of DMPC populations in human dermis, consistent with data from MSCs in human bone marrow, and with the loss of CD34 we observed from both ASCs and DMPCs on cell culture. These data enable future study of DMPCs in health and disease, and may also explain why some mesenchymal cell lines derived from human dermis exhibit characteristics of MSCs.