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人毛囊源性间充质干细胞静脉移植改善骨质疏松小鼠的小梁骨丢失

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

作者信息

Lin Longshuai, He Enjun, Wang Hongjie, Guo Weihong, Wu Zhenkai, Huang Kai, Zhao Qinghua

机构信息

Department of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Pediatric Orthopaedics, Shanghai Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Cell Dev Biol. 2022 Mar 10;10:814949. doi: 10.3389/fcell.2022.814949. eCollection 2022.

DOI:10.3389/fcell.2022.814949
PMID:35359450
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8960386/
Abstract

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. 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 . 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. 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. 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.

摘要

毛囊中含有丰富的自体干细胞库,人毛囊来源的间充质干细胞(hHF-MSCs)具有多向分化潜能。包括hHF-MSCs在内的多种间充质干细胞来源,已成为细胞治疗、再生医学和组织工程领域颇具吸引力的候选对象。本研究旨在探讨静脉注射hHF-MSCs对骨质疏松小鼠骨量的影响及其机制,并为hHF-MSCs治疗骨质疏松的临床应用提供前景。从健康志愿者头皮枕部区域物理拔出约20根带有完整毛囊的毛发,提取毛囊来源的成纤维细胞样细胞。对这些细胞进行培养和鉴定。对去卵巢诱导的和与年龄相关的骨质疏松SCID小鼠进行静脉注射hHF-MSCs以治疗骨质疏松。在第二次注射后7周处死小鼠并收集样本。收集长骨和L1椎体进行显微CT扫描、组织形态计量学和免疫组织化学分析。收集外周血清进行ELISA分析和抗体芯片检测。毛囊来源的成纤维细胞样细胞被定义为hHF-MSCs。静脉注射hHF-MSCs能更好地恢复骨质疏松小鼠的小梁骨量。双荧光素标记测定、骨陷窝染色和外周血清ELISA分析显示,移植后骨形成增强,骨吸收减弱。抗体芯片和免疫组织化学分析表明,包括骨保护素(OPG)、Wnt2b、头蛋白(Noggin)、血管细胞黏附分子-1(VCAM-1)和核因子κB受体活化因子配体(RANKL)在内的几种细胞因子可能参与了这一过程。人HF-MSCs移植可对抗小鼠绝经和衰老诱导的小梁骨丢失。并且上述hHF-MSCs移植抑制骨吸收和促进骨形成的机制与OPG、Wnt2b、VCAM-1、Noggin和RANKL有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c3/8960386/eeacb15cb19c/fcell-10-814949-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6c3/8960386/90dd247b027c/fcell-10-814949-g001.jpg
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Impact of human mesenchymal cells of different body site origins on the maturation of dermo-epidermal skin substitutes.不同身体部位来源的人间充质细胞对真皮-表皮皮肤替代物成熟的影响。
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