Abstract
The vascular wall within adipose tissue is a source of mesenchymal progenitors, referred to as perivascular stem/stromal cells (PSC). PSC are isolated via fluorescence activated cell sorting (FACS), and defined as a bipartite population of pericytes and adventitial progenitor cells (APCs). Those factors that promote the differentiation of PSC into bone or fat cell types are not well understood. Here, we observed high expression of WISP-1 among human PSC in vivo, after purification, and upon transplantation in a bone defect. Next, modulation of WISP-1 expression was performed, using WISP-1 overexpression, WISP-1 protein, or WISP-1 siRNA. Results demonstrated that WISP-1 is expressed in the perivascular niche, and high expression is maintained after purification of PSC, and upon transplantation in a bone microenvironment. In vitro studies demonstrate that WISP-1 has pro-osteogenic/anti-adipocytic effects in human PSC, and that regulation of BMP signaling activity may underlie these effects. In summary, our results demonstrate the importance of the matricellular protein WISP-1 in regulation of the differentiation of human stem cell types within the perivascular niche. WISP-1 signaling upregulation may be of future benefit in cell therapy mediated bone tissue engineering, for the healing of bone defects or other orthopaedic applications.
Highlights
The vascular wall within adipose tissue is a source of mesenchymal stromal progenitors, often referred to as perivascular stem/stromal cells (PSC), vascular wall resident mesenchymal stem cell (MSC), or tissue-specific MSC
WISP-1 protein is highly expressed across vessel types in human adipose tissue, in a distribution that includes both presumptive microvascular pericytes and adventitial progenitor cells (APCs)
We have elucidated a new role of WISP-1 signaling within stromal progenitor cells of the perivascular niche of human adipose tissue
Summary
The vascular wall within adipose tissue is a source of mesenchymal stromal progenitors, often referred to as perivascular stem/stromal cells (PSC), vascular wall resident mesenchymal stem cell (MSC), or tissue-specific MSC. As an alternative cell source, PSC from subcutaneous white adipose tissue are an uncultured, fluorescence activated cell sorting (FACS) derived cell population, and are defined as a bipartite population of CD146+CD34−CD45−CD31− pericytes and CD34+CD146-CD45-CD31- adventitial progenitor cells (APCs)[6,7] Their location and antigen expression differ, pericytes and APCs have conserved and overlapping pro-osteogenic/pro-vasculogenic properties in the context of bone tissue engineering (see[8] for a review). In comparison to cells from the SVF of the same patient sample, PSC have shown significantly greater potential for bone formation by their ability to form bone in an intramuscular location[7,11], calvarial defect model[12], or rat spinal fusion model[6,11] Those factors that maintain quiescence or promote the differentiation of PSC into bone or fat cell types are not well understood. These observations led us to examine the localization and function of WISP-1 within the perivascular niche and in human PSC
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