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

Stefano Negri, Yiyun Wang, Takashi Sono, Seungyong Lee, Ginny Ching Yun Hsu, Jiajia Xu, Carolyn A. Meyers, Qizhi Qin, Kristen Broderick, Kenneth W. Witwer, Bruno Peault, Aaron W. James

Research output: Contribution to journalArticlepeer-review

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 factors overexpressed by PSCs which may explain their negative regulation of graft resorption. In summary, PSCs reduce osteoclast formation and prevent bone graft resorption in high turnover states such as gonadectomy-induced osteoporosis.

Original languageEnglish (US)
Pages (from-to)1617-1630
Number of pages14
JournalStem Cells Translational Medicine
Volume9
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • adipose stem cell
  • bone graft
  • mesenchymal stem cell
  • osteoclast
  • pericyte
  • perivascular stem cell
  • spine fusion

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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