Therapy using periosteal cells cultivated in microgravity or their secretome improves bone in osteoporotic rats: a proof-of-concept study

Recent work suggests that periosteal cells (PCs) cultivated in simulated microgravity have properties predicted to be pro-osteogenic. This has important implications for the treatment of osteoporosis. The present study aims to evaluate the performance of this technology for improving osteoporosis treatment. Sixty osteoporotic rats (12 per group) received single intravenous doses of: bisphosphonate (Positive Control Group–PCG); saline solution (Negative Control Group–NCG); PCs cultivated under simulated microgravity (POCMG), or secretome of PCs cultivated under simulated microgravity (PSMG). In a Control Group (CG), SHAM surgeries were performed. Half of the animals were euthanized after 14 days (T1) and the other half after 42 days. The right femurs were submitted to microCT (for mineralized tissue and cortical bone thickness measurement) and to histomorphometric analysis (for bone, collagen tissue and medullary space measurement). The left femurs were submitted to molecular analysis for gene expression profiling of bone metabolism markers and regulators of bone turnover. At T1, mineralized tissue was equivalent among PCG, POCMG, PSMG and CG and all these groups had significantly higher levels when compared with NCG (p < 0.05). At T2, NCG had the lowest mineralized tissue (p < 0.05), followed by POCMG, PSMG, PCG and CG. There was no significant difference between PCG and PSMG, between CG and PCG and between POCMG and PSMG. PSMG had a thicker cortical plate when compared with NCG, PCG and CG (p < 0.05), and equivalent when compared with POCMG. The histomorphometry showed no difference between timepoints for bone, collagen tissue and medullary space in all groups. For the intergroup comparison, the histomorphometric analysis showed a lower level of bone tissue and higher measurement of medullary space for NCG when compared with the other groups (p < 0.05). For collagen tissue, no statistically significant difference was shown between all groups. The molecular analysis showed no statistical difference among groups. The use of PCs cultivated under microgravity and their secretome improved mineralized tissue amount in osteoporotic rats. The effects of the secretome on bone gain were equivalent to those of bisphosphonates, and the secretome showed superior results in improving cortical bone thickness.