Abstract
Human osteogenic progenitors are not precisely defined, being primarily studied as heterogeneous multipotent cell populations and termed mesenchymal stem cells (MSCs). Notably, select human pericytes can develop into bone-forming osteoblasts. Here, we sought to define the differentiation potential of CD146+ human pericytes from skeletal and soft tissue sources, with the underlying goal of defining cell surface markers that typify an osteoblastogenic pericyte. CD146+CD31−CD45− pericytes were derived by fluorescence-activated cell sorting from human periosteum, adipose, or dermal tissue. Periosteal CD146+CD31−CD45− cells retained canonical features of pericytes/MSC. Periosteal pericytes demonstrated a striking tendency to undergo osteoblastogenesis in vitro and skeletogenesis in vivo, while soft tissue pericytes did not readily. Transcriptome analysis revealed higher CXCR4 signaling among periosteal pericytes in comparison to their soft tissue counterparts, and CXCR4 chemical inhibition abrogated ectopic ossification by periosteal pericytes. Conversely, enrichment of CXCR4+ pericytes or stromal cells identified an osteoblastic/non-adipocytic precursor cell. In sum, human skeletal and soft tissue pericytes differ in their basal abilities to form bone. Diversity exists in soft tissue pericytes, however, and CXCR4+ pericytes represent an osteoblastogenic, non-adipocytic cell precursor. Indeed, enrichment for CXCR4-expressing stromal cells is a potential new tactic for skeletal tissue engineering.
Highlights
Visualization, isolation, and characterization of human CD146+ periosteal pericytes Pericytes were first visualized within human periosteum as a CD146 (Mel-CAM) expressing perivascular cell population (Fig. 1)
Human periosteal pericytes were isolated as the CD146+CD31−CD45− fraction of the enzymatic digestion of human periosteum, using methods adapted from adipose tissue[3] (Fig. 1d)
No expression of CD31 or CD45 was seen among CD146+CD31−CD45− pericytes (Fig. 1e)
Summary
Beyond being a conduit for gas exchange, the vasculature houses mesenchymal progenitor cells that actively participate in tissue renewal and repair.[1,2] A perivascular niche for mesenchymal stem/stromal cells (MSCs) has been observed across organ systems,[3,4,5,6] and in human tissues microvascular CD146+ pericytes are best studied as a cellular forerunner of conventional, culture-derived MSCs.[7,8]. Understanding how pericytes regenerate their own tissue microenvironment, or adopt a heterologous cellular fate, is of central importance for cell-based efforts in regenerative medicine
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
