Human perivascular stem cells prevent bone graft resorption in osteoporotic contexts by inhibiting osteoclast formation
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jul 22, 2020
- Source ID
- 10.1002/sctm.20-0152
Entities
People
- Aaron W James
- Bruno Peault
- Carolyn A. Meyers
- Ginny Ching-yun Hsu
- Jiajia Xu
- Kenneth W. Witwer
- Kristen Broderick
- Qizhi Qin
- Seungyong Lee
- Stefano Negri
- Takashi Sono
- Yiyun Wang
Organizations
- American Cancer Society
- Johns Hopkins University
- Musculoskeletal Transplant Foundation
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- National Institute of Dental and Craniofacial Research
- United States Department of Defense
- University of California, Los Angeles
- University of Edinburgh
- University of Verona