Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cell (ATMSC) Expressing Alpha-1 Antitrypsin Reduces Bone Loss in Ovariectomized Osteoporosis Mice.

Osteoporosis is a common health problem severely affecting the quality of life of many people, especially women. Current treatment options for osteoporosis are limited due to their association with several side-effects and moderate efficacy. Therefore, novel therapies for osteoporosis are needed. This study tested the feasibility of adipose tissue-derived mesenchymal stem cell (ATMSC)-based human alpha-1 antitrypsin (hAAT, SERPINA1) gene therapy for the prevention of bone loss in an ovariectomized (OVX) mouse model. Eight-week-old female C57BL6 mice underwent ovariectomy and were treated with hAAT (protein therapy), ATMSC (stem-cell therapy), ATMSC + hAAT (combination of ATMSC and hAAT therapy), and ATMSCs infected with lentiviral vectors expressing hAAT (ATMSC-based hAAT gene therapy). The study showed that lenti-hAAT vector-infected ATMSCs (ATMSC-LV-hAAT) produced high levels of hAAT. Transplantation of these cells significantly decreased OVX-induced serum levels of interleukin 6 and interleukin 1 beta, and receptor activator of nuclear factor kappa B gene expression levels in bone tissue. Immunohistological analysis revealed that transplanted cells migrated to the bone tissue and secreted hAAT. Importantly, bone microstructure analysis by microcomputerized tomography showed that this treatment significantly protected against OVX-induced bone loss. The results suggest a novel strategy for the treatment of osteoporosis in humans.