State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi'an, Shaanxi Province, China.
PLoS One. 2013 Apr 30;8(4):e62363. doi: 10.1371/journal.pone.0062363. Print 2013.
Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) have been studied for damaged liver repair; however, the conclusions drawn regarding their homing capacity to the injured liver are conflicting. Besides, the relative utility and synergistic effects of these two cell types on the injured liver remain unclear.
METHODOLOGY/PRINCIPAL FINDINGS: MSCs, HSCs and the combination of both cells were obtained from the bone marrow of male mice expressing enhanced green fluorescent protein(EGFP)and injected into the female mice with or without liver fibrosis. The distribution of the stem cells, survival rates, liver function, hepatocyte regeneration, growth factors and cytokines of the recipient mice were analyzed. We found that the liver content of the EGFP-donor cells was significantly higher in the MSCs group than in the HSCs or MSCs+HSCs group. The survival rate for the MSCs group was significantly higher than that of the HSCs or MSCs+HSCs group; all surpassed the control group. After MSC-transplantation, the injured livers were maximally restored, with less collagen than the controls. The fibrotic areas had decreased to a lesser extent in the mice transplanted with HSCs or MSCs+HSCs. Compared with mice in the HSCs group, the mice that received MSCs had better improved liver function. MSCs exhibited more remarkable paracrine effects and immunomodulatory properties on hepatic stellate cells and native hepatocytes in the treatment of the liver pathology. Synergistic actions of MSCs and HSCs were most likely not observed because the stem cells in liver were detected mostly as single cells, and single MSCs are insufficient to provide a beneficial niche for HSCs.
CONCLUSIONS/SIGNIFICANCE: MSCs exhibited a greater homing capability for the injured liver and modulated fibrosis and inflammation more effectively than did HSCs. Synergistic effects of MSCs and HSCs were not observed in liver injury.
间充质干细胞（MSCs）和造血干细胞（HSCs）已被用于受损肝脏的修复研究；然而，关于它们向受损肝脏归巢的能力的结论存在争议。此外，这两种细胞类型对受损肝脏的相对效用和协同作用尚不清楚。
方法/主要发现：从表达增强型绿色荧光蛋白（EGFP）的雄性小鼠的骨髓中获取 MSCs、HSCs 以及这两种细胞的混合物，并将其注射到有或没有肝纤维化的雌性小鼠体内。分析了受者小鼠的干细胞分布、存活率、肝功能、肝细胞再生、生长因子和细胞因子。我们发现，MSC 组的 EGFP 供体细胞在肝脏中的含量明显高于 HSCs 组或 MSC+HSCs 组。MSC 组的存活率明显高于 HSCs 组或 MSC+HSCs 组；均超过对照组。MSC 移植后，受损肝脏得到最大程度的恢复，胶原含量低于对照组。接受 HSCs 或 MSC+HSCs 移植的小鼠纤维化区域减少程度较小。与 HSCs 组的小鼠相比，接受 MSCs 的小鼠肝功能得到了更好的改善。MSC 在治疗肝病理方面对肝星状细胞和固有肝细胞表现出更显著的旁分泌作用和免疫调节特性。由于在肝脏中检测到的干细胞主要为单个细胞，并且单个 MSC 不足以为 HSCs 提供有益的龛位，因此 MSCs 和 HSCs 之间可能没有观察到协同作用。
结论/意义：MSCs 对受损肝脏具有更强的归巢能力，并且比 HSCs 更有效地调节纤维化和炎症。在肝损伤中未观察到 MSCs 和 HSCs 的协同作用。
