Liao Xinbo, Li Feng, Wang Xujung, Yanoso Jacquelyn, Niyibizi Christopher
Pennsylvania State University College of Medicine, Department of Orthopaedics and Rehabilitation, Division of Musculoskeletal Sciences, Hershey PA 17033, USA.
Stem Cells Dev. 2008 Apr;17(2):303-14. doi: 10.1089/scd.2007.0086.
Systemic delivery of mesenchymal stem cells (MSCs) or stromal cells in vivo is attractive because it offers means of disseminating therapeutic cells to various tissues and organs in vivo. In the present study, we investigated the distribution and engraftment of the murine adipose-derived mesenchymal stem cells (ADSCs) without exposure to or exposed to bone microenvironment or transforming growth factor-beta1 (TGF-beta1) prior to transplantation into developing mice. The ADSCs harvested from the murine inguinal fat pad exhibited potential for differentiation toward osteogenic and adipogenic cell lineages in vitro. Fourteen days after systemic transplantation of the ADSCs marked with enhanced green fluorescent protein (EGFP) into developing mice, minimal donor GFP(+) cells were detected in the skeletal tissues in a limited number of the recipient mice. Exposure of the ADSCs to bone microenvironment for 7 or 14 days prior to transplantation into developing mice enhanced their migration and survival in the bones of the recipient mice. Exposure of ADSCs to TGF-beta1 prior to systemic transplantation exerted similar effects on cell migration and engraftment in various tissues, including the bones of the recipient developing mice. At 28 days following systemic transplantation, the ADSCs exposed to bone microenvironment were restricted mostly to the skeletal tissues of the recipient mice. Donor cells retrieved from the bones of the recipient mice at 28 days following cell transplantation expressed the differentiation markers Runx2 and Osterix (Osx). These data suggest that exposure of ADSCs to bone microenvironment or to TGF-beta1 prior to transplantation enhances their survival in the skeletal tissues following transplantation.
间充质干细胞（MSCs）或基质细胞的体内系统性递送具有吸引力，因为它提供了将治疗性细胞扩散到体内各种组织和器官的手段。在本研究中，我们调查了在移植到发育中的小鼠体内之前，未暴露于或暴露于骨微环境或转化生长因子-β1（TGF-β1）的小鼠脂肪来源间充质干细胞（ADSCs）的分布和植入情况。从小鼠腹股沟脂肪垫收获的ADSCs在体外表现出向成骨和成脂细胞谱系分化的潜力。将用增强型绿色荧光蛋白（EGFP）标记的ADSCs系统性移植到发育中的小鼠体内14天后，在少数受体小鼠的骨骼组织中检测到极少的供体GFP(+)细胞。在移植到发育中的小鼠体内之前，将ADSCs暴露于骨微环境7天或14天可增强它们在受体小鼠骨骼中的迁移和存活。在系统性移植之前将ADSCs暴露于TGF-β1对细胞在包括受体发育中小鼠骨骼在内的各种组织中的迁移和植入产生类似影响。系统性移植后28天，暴露于骨微环境的ADSCs大多局限于受体小鼠的骨骼组织中。在细胞移植后28天从受体小鼠骨骼中回收的供体细胞表达了分化标志物Runx2和Osterix（Osx）。这些数据表明，在移植前将ADSCs暴露于骨微环境或TGF-β1可提高它们在移植后骨骼组织中的存活率。
