Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice
Transplantation of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells or Their Conditioned Medium Prevents Bone Loss in Ovariectomized Nude Mice
复制标题
DOI：
10.1089/ten.tea.2012.0047
复制
发表时间：
2013-03-01
影响因子：
4.1
通讯作者：
Shin, Chan Soo
中科院分区：
文献类型：
--
作者：
An, Jee Hyun;Park, Hyojung;Shin, Chan Soo
脐带血（UCB）最近被确认为用于干细胞治疗的间充质干细胞（MSCs）的一个新来源。我们研究了系统性注射人脐带血间充质干细胞及其条件培养基（CM）对去卵巢（OVX）诱导的裸鼠骨质流失的影响。将10周龄的雌性裸鼠分为6组：假手术并用溶媒处理的小鼠（假手术 - 溶媒组），接受脐带血间充质干细胞（OVX - MSC组）或人皮肤成纤维细胞（OVX - DFB组）移植的去卵巢小鼠，用脐带血间充质干细胞条件培养基（OVX - CM组）、唑来膦酸（OVX - Zol组）或溶媒（OVX - 溶媒组）处理的去卵巢小鼠。尽管与假手术 - 溶媒组相比，OVX - 溶媒组的骨矿物质密度（BMD）增加显著较少，但人脐带血间充质干细胞的移植（OVX - MSC组）有效地防止了去卵巢诱导的骨量减少。值得注意的是，OVX - CM组也显示出与OVX - MSC组相当的骨密度保持。此外，微计算机断层扫描分析表明，与OVX - 溶媒组或OVX - DFB组相比，OVX - MSC组和OVX - CM组的骨小梁参数均得到改善。组织形态计量学分析显示，OVX - MSC组和OVX - CM组小鼠的骨形成参数增加，同时血清I型前胶原N - 端肽水平升高。然而，细胞示踪分析未能证明在细胞输注48小时后间充质干细胞在骨组织中的植入。在体外，人脐带血间充质干细胞条件培养基增加了人骨髓来源的间充质干细胞的碱性磷酸酶（ALP）活性以及C3H10T1/2细胞中I型胶原、Runx2、osterix和ALP的mRNA表达。此外，人脐带血间充质干细胞条件培养基显著增加了类骨细胞MLO - Y4细胞的存活率，同时抑制了破骨细胞分化。总之，人脐带血间充质干细胞的移植可有效防止去卵巢介导的裸鼠骨质流失，这似乎是由旁分泌机制而非间充质干细胞的直接植入所介导的。
Umbilical cord blood (UCB) has recently been recognized as a new source of mesenchymal stem cells (MSCs) for use in stem cell therapy. We studied the effects of systemic injection of human UCB-MSCs and their conditioned medium (CM) on ovariectomy (OVX)-induced bone loss in nude mice. Ten-week-old female nude mice were divided into six groups: Sham-operated mice treated with vehicle (Sham-Vehicle), OVX mice subjected to UCB-MSCs (OVX-MSC), or human dermal fibroblast (OVX-DFB) transplantation, OVX mice treated with UCB-MSC CM (OVX-CM), zoledronate (OVX-Zol), or vehicle (OVX-Vehicle). Although the OVX-Vehicle group exhibited significantly less bone mineral density (BMD) gain compared with the Sham-Vehicle group, transplantation of hUCB-MSCs (OVX-MSC group) has effectively prevented OVX-induced bone mass attenuation. Notably, the OVX-CM group also showed BMD preservation comparable to the OVX-MSC group. In addition, microcomputed tomography analysis demonstrated improved trabecular parameters in both the OVX-MSC and OVX-CM groups compared to the OVX-Vehicle or OVX-DFB group. Histomorphometric analysis showed increased bone formation parameters, accompanied by increased serum procollagen type-I N-telopeptide levels in OVX-MSC and OVX-CM mice. However, cell-trafficking analysis failed to demonstrate engraftment of MSCs in bone tissue 48 h after cell infusion. In vitro, hUCB-MSC CM increased alkaline phosphatase (ALP) activity in human bone marrow-derived MSCs and mRNA expression of collagen type 1, Runx2, osterix, and ALP in C3H10T1/2 cells. Furthermore, hUCB-MSC CM significantly increased survival of osteocyte-like MLO-Y4 cells, while it inhibited osteoclastic differentiation. To summarize, transplantation of hUCB-MSCs could effectively prevent OVX-mediated bone loss in nude mice, which appears to be mediated by a paracrine mechanism rather than direct engraftment of the MSCs.