Efficacy of autologous bone marrow derived Mesenchymal stem cells (MSCs), osteoblasts and osteoblasts derived exosome in the reversal of ovariectomy (OVX) induced osteoporosis in rabbit model

Background: A recent study showed that OVX-induced osteoporosis was reversed after injection of osteoblasts cultured from the bone marrow in rats. The present study evaluated the effect of injecting MSCs, osteoblasts, and exosomes isolated from osteoblasts for the treatment of osteoporosis in the rabbit model. Methods: Osteoporosis was created in 40 rabbits by performing ovareictomy at 6 months of age, and 1 mg/kg body weight of methyl prednisolone sodium succinate was injected daily for 8 weeks. Animals were fed twice daily and were given water ad libitum. MSCs and osteoblasts were grown from the bone marrow as per the methodology described earlier. From osteoblasts, exosomes were extracted. After the 15th day, MSCs (Group 2), osteoblasts (Group 3), and exosomes (Group 4) were injected into 5 animals each, and 0.5 ml of normal saline were injected into the control group (Group 1). After 12 weeks (11 months of age), all the animals were euthanized. The whole femur and the lumbar vertebrae 3-5 were dissected out and were subjected to radiological assessment using high-resolution peripheral quantitative computerized tomography (HRpQCT). All parameters of the bone volume, trabecular number, thickness, and spacing were assessed using SPSS (Statistical Package for the Social Sciences), version 21.0, Chicago, Illinois. A p value of <0.05 was considered Statistically significant with a confidence interval (CI) of 95%. Results: Structural indices of the osteoblasts-injected animals were significantly better than the control group for the distal femur. The most significant improvement was seen in the osteoblasts, MSCs, and exosomes group in that order. The p value of all parameters was <0.0001 in the osteoblasts group, whereas the total and bone volume had a lower p value in the MSCs group. In the osteoblasts group, the positive changes were similar in the distal femur and lumbar vertebrae, but with MSCs and exosomes, the changes were more pronounced in the vertebral spine than the distal femur. Conclusions: This study shows that autologous bone marrow-derived osteoblasts have the robust influence of reversing OVX-induced osteoporosis in rabbits.