Cell-gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China; Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-Sen University, Guangzhou, China.
Biomaterials. 2015 May;50:56-66. doi: 10.1016/j.biomaterials.2015.01.029. Epub 2015 Feb 14.
Renal resident mesenchymal stem cells (MSCs) are important regulators of kidney homeostasis, repair or regeneration. However, natural distribution and the starting population properties of these cells remain elusive because of the lack of specific markers. Here, we identified post-natal kidney derived Nestin(+) cells that fulfilled all of the criteria as a mesenchymal stem cell. These isolated Nestin(+) cells expressed the typical cell-surface marker of MSC, including Sca-1, CD44, CD106, NG2 and PDGFR-α. They were capable of self-renewal, possessed high clonogenic potential and extensive proliferation for more than 30 passages. Under appropriate differentiation conditions, these cells could differentiate into adipocytes, osteocytes, chondrocytes and podocytes. After intravenous injection into acute kidney injury mice, Nestin(+) cells contributed to functional improvement by significantly decreasing the peak level of serum creatinine and BUN, and reducing the damaged cell apoptosis. Furthermore, conditioned medium from Nestin(+) cells could protect against ischemic acute renal failure partially through paracrine factor VEGF. Taken together, our findings indicate that renal resident Nestin(+) MSCs can be derived, propagated, differentiated, and repair the acute kidney injury, which may shed new light on understanding MSCs biology and developing cell replacement therapies for kidney disease.
肾固有间充质干细胞（MSCs）是肾脏内稳态、修复或再生的重要调节者。然而，由于缺乏特异性标志物，这些细胞的自然分布和起始群体特性仍难以捉摸。在这里，我们鉴定了出生后肾脏来源的巢蛋白（Nestin）阳性细胞，这些细胞满足间充质干细胞的所有标准。这些分离的巢蛋白阳性细胞表达 MSC 的典型细胞表面标志物，包括 Sca-1、CD44、CD106、NG2 和 PDGFR-α。它们具有自我更新能力，具有高克隆形成潜力，可在 30 代以上的时间内大量增殖。在适当的分化条件下，这些细胞可以分化为脂肪细胞、成骨细胞、软骨细胞和足细胞。静脉注射到急性肾损伤小鼠体内后，巢蛋白阳性细胞通过显著降低血清肌酐和 BUN 的峰值水平以及减少受损细胞凋亡，有助于改善肾功能。此外，巢蛋白阳性细胞的条件培养基可通过旁分泌因子 VEGF 部分保护缺血性急性肾衰竭。综上所述，我们的研究结果表明，肾脏固有巢蛋白阳性 MSC 可以被分离、扩增、分化，并修复急性肾损伤，这可能为理解 MSC 生物学和开发肾脏疾病的细胞替代治疗方法提供新的思路。
