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.
Highlights
Mesenchymal stem cells (MSCs) are multipotent stem cells which are capable to self-renew and differentiate into different kinds of tissues (Caplan, 2007; da Silva Meirelles et al, 2006), including bone, muscle, adipose, tendons, neurons, and myocardium, under specific in vivo and in vitro conditions (Bruder et al, 1998; Ferrari et al, 1998; Young et al, 1998; Dennis et al, 1999; Qian and Saltzman, 2004; Miao et al, 2017)
RT-qPCR showed that osteogenesis marker genes including Runx2, Opn and Ocn were activated in response to osteogenic induction (Figure 2B)
Studies have reported that multipotent MSCs can be derived from the root tissue of hair follicles by directly plucking the human hair (Wang et al, 2013), and that these HF-MSCs share the common characteristics with other types of MSCs
Summary
Mesenchymal stem cells (MSCs) are multipotent stem cells which are capable to self-renew and differentiate into different kinds of tissues (Caplan, 2007; da Silva Meirelles et al, 2006), including bone, muscle, adipose, tendons, neurons, and myocardium, under specific in vivo and in vitro conditions (Bruder et al, 1998; Ferrari et al, 1998; Young et al, 1998; Dennis et al, 1999; Qian and Saltzman, 2004; Miao et al, 2017). MSCs have no risk of teratoma formation and no ethical issues (Kassem et al, 2004; Augello et al, 2010) All of these properties make MSCs an attractive candidate for cell therapy, regenerative medicine and tissue engineering. Many sources of MSCs have been used in the clinical setting They are generally divided into: adult MSCs from bone marrow (BM), adipose tissue, peripheral blood, and dental pulp, and the neonatal tissue-derived MSCs from placenta, amnion, and umbilical cord (Rodríguez-Fuentes et al, 2021). Hair follicles are accessible and harbor a rich autologous stem cell pool with multi-lineage (myogenic, osteogenic, adipogenic and chondrogenic lineages) differentiation potential. Hair follicles harbor a rich autologous stem cell pool and human hair folliclederived 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
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