Human perivascular stem cells prevent bone graft resorption in osteoporotic contexts by inhibiting osteoclast formation.

Stem Cells Translational Medicine
Stefano NegriAaron W James

Abstract

The vascular wall stores mesenchymal progenitor cells which are able to induce bone regeneration, via direct and paracrine mechanisms. Although much is known regarding perivascular cell regulation of osteoblasts, their regulation of osteoclasts, and by extension utility in states of high bone resorption, is not known. Here, human perivascular stem cells (PSCs) were used as a means to prevent autograft resorption in a gonadectomy-induced osteoporotic spine fusion model. Furthermore, the paracrine regulation by PSCs of osteoclast formation was evaluated, using coculture, conditioned medium, and purified extracellular vesicles. Results showed that PSCs when mixed with autograft bone induce an increase in osteoblast:osteoclast ratio, promote bone matrix formation, and prevent bone graft resorption. The confluence of these factors resulted in high rates of fusion in an ovariectomized rat lumbar spine fusion model. Application of PSCs was superior across metrics to either the use of unpurified, culture-defined adipose-derived stromal cells or autograft bone alone. Under coculture conditions, PSCs negatively regulated osteoclast formation and did so via secreted, nonvesicular paracrine factors. Total RNA sequencing identified secreted...Continue Reading

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Citations

Jan 30, 2021·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Ginny Ching-Yun HsuAaron W James

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Methods Mentioned

BETA
xenograft
scanning electronic microscopy
fluorescence imaging

Key Resources (RRID) Mentioned

SCR_017396
SCR_011853
SCR_011860
SCR_008858

Software Mentioned

GraphPad
Partek Genomics Suite
Spotfire DecisopnSite with Functional Genomics
ImageJ
GraphPad Prism
Skyscan CTan
CLC Genomics Server and Workbench
DataViewer
Nanosight

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