Intravenous Transplantation of Human Hair Follicle-Derived Mesenchymal Stem Cells Ameliorates Trabecular Bone Loss in Osteoporotic Mice

Abstract

Background: Hair follicles harbor a rich autologous stem cell pool and human hair follicle-derived mesenchymal stem cells (hHF-MSCs) have multi-lineage differentiation potential. Many sources of MSCs include hHF-MSCs have been attractive candidates for cell therapy, regenerative medicine and tissue engineering. The present study is to explore the effect of intravenous transplantation of hHF-MSCs on bone mass in osteoporotic mice and its mechanism, and provides prospects for clinical applications for the treatment of osteoporosis with hHF-MSCs.Methods: Physically pull out about 20 hairs with intact hair follicles from the occipital area of the scalp of healthy volunteers, and extract hair follicle-derived fibroblast-like cells. These cells were cultured and characterized in vitro. Intravenous injection of hHF-MSCs was performed on ovariectomy-induced and age-related osteoporotic SCID mice for osteoporosis treatment. The mice were sacrificed 7 weeks after the second injection and samples were collected. The long bones and L1 vertebrae were collected for micro-CT scan, histomorphometry and immunohistochemical analysis. Peripheral serum were collected for ELISA analysis and antibody array.Results: Hair follicle-derived fibroblast-like cells were defined as hHF-MSCs. Intravenous transplantation of hHF-MSCs can better restores trabecular bone mass in osteoporotic mice. The double calcein labeling assay, trap staining of bones and ELISA analysis in peripheral serum showed enhanced bone formation and weakened bone resorption after transplantation. Antibody array and immunohistochemical analysis showed that several cytokines including OPG, Wnt2b, Noggin, VCAM-1 and RANKL might be involved in this process.Conclusion: Human HF-MSCs transplantation can combat trabecular bone loss induced by menopause and aging in mice. And the above mechanism that hHF-MSCs transplantation inhibits bone resorption and promote bone formation is related to OPG, Wnt2b, VCAM-1, Noggin and RANKL.

miR-134-5p inhibits osteoclastogenesis through a novel miR-134-5p/Itgb1/MAPK pathway

“…For osteoclastogenesis assays, we isolated BMMs from 6week-old C57BL/6N mice and cultured them in complete minimum essential medium eagle alpha modifications (α-MEM) medium with M-CSF (30 ng/ml) and RANKL (50 ng/ ml) for 7 days as described previously (63). In brief, the femurs and tibias of 6-week-old mice were surgically removed, and the bone marrow was flushed out with warm, serum-free α-MEM medium using a 1 ml syringe.…”

Mechanistic advances in osteoporosis and anti‐osteoporosis therapies

“…277 Therefore, EVs containing paracrine factors, which are isolated from MSC conditioned medium, offer a strategy for cell-free MSC therapy. 278,279 Several studies have shown that human-derived MSCs can enhance osteogenesis and prevent OVX-mediated bone loss in mice, [280][281][282] but the specific mechanism is unclear. Wang et al 283 analyzed the metabolomics of mice that received BMSC transplantation, suggesting that exogenous BMSC may play an anti-osteoporosis role by maintaining estrogen levels to mediate adipogenesis and osteoblastic metabolism in bone.…”

“…Several studies have shown that human‐derived MSCs can enhance osteogenesis and prevent OVX‐mediated bone loss in mice, 280–282 but the specific mechanism is unclear. Wang et al 283 .…”