Human pericytes isolated from adipose tissue have better differentiation abilities than their mesenchymal stem cell counterparts

Abstract

Multi-potent mesenchymal stem/progenitor cells are present in almost all organs and tissues, although their identity remains elusive. Several isolation strategies have been pursued to identify these cells prospectively, leading to the isolation of various cell populations endowed with multi-lineage mesodermal potential. Historically, mesenchymal stem cells (MSCs) were the first cell population to be isolated from the stromal fraction of most connective tissues. These cells are able to differentiate towards various mesodermal lineages and are currently the most studied adult mesodermal progenitors. Recently, the isolation of a subpopulation of microvascular pericytes (PCs) endowed with multi-lineage mesodermal potential has led to the identification of mesenchymal progenitors that reside in a defined anatomical location, namely the wall of small blood vessels. To gain insight into these two related cell populations, we performed a detailed analysis of the mesodermal potential of isogenic human MSCs and PCs isolated from white adipose tissue. Although both cell populations expressed known mesodermal markers at similar levels and displayed a comparable growth rate, PCs differentiated towards osteocytes, adipocytes and myocytes more efficiently than their MSC counterparts, as revealed by both histological and molecular assays. Our results show that microvascular PCs are more prone to mesenchymal differentiation than MSCs and therefore represent a preferable source of human adult mesenchymal progenitors when adipose tissue is used as a cell source.

Tissue-Specific Cultured Human Pericytes: Perivascular Cells from Smooth Muscle Tissue Have Restricted Mesodermal Differentiation Ability

“…FC analysis indicated that all cell populations stained positive for the surface antigens CD13, CD44, CD146, and NG2 (Fig. 1A), in agreement with previously reported analysis on in vitro [12,25] and in vivo [13] microvascular PCs from skeletal muscle and adipose tissue.…”

“…1, we concluded that sk-hPCs and sm-hPCs share the same immunophenotypic and molecular profile. According to previous data on PCs from adipose tissue [25], these findings indicate that cultured PCs isolated from different sources without exploiting any additional cell selection are virtually indistinguishable. However, when we compared multipotent differentiation abilities of sk-hPCs and sm-hPCs, we observed that sk-hPCs were able to differentiate into adipocytes, osteocytes, skeletal, and smooth muscle cells, whereas sm-hPCs were only able to give rise to smooth muscle cells.…”

“…3B, p-r). Similarly, neither a-Actinin-positive cells nor multinucleated myotubes were observed when sm-hPCs were even cocultured with the mouse C2C12 cells (data not shown), which enhance the ability of human adipose tissue-derived PCs to form myotubes [25].…”

“…In addition, we recently reported that hPCs isolated from skeletal and adipose tissues are yet endowed with multipotent mesodermal abilities, but sk-hPCs differentiate at much more efficient rate than at-hPCs [25]. Taken together, all these evidences indicate that hPCs isolated from different tissues cannot be considered equivalent in terms of their differentiation potentials.…”

“…PCs from human skeletal muscle are also able to differentiate toward additional lineages of mesodermal origin such as adipocytes, osteocytes, and chondrocytes [12]. However, a comparative analysis of PCs from different human tissues indicated that PCs from skeletal muscle could differentiate toward mesodermal lineages more efficiently than PCs from adipose tissue [25]. In addition, PCs from adult heart are not able to differentiate into skeletal muscle cells, but only into cardiac myocytes, adipocytes, osteocytes, and chondrocytes [26].…”