Franchi Federico, Peterson Karen M, Xu Rende, Miller Brent, Psaltis Peter J, Harris Peter C, Lerman Lilach O, Rodriguez-Porcel Martin
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
Cell Transplant. 2015;24(9):1687-98. doi: 10.3727/096368914X684619. Epub 2014 Oct 6.
Polycystic kidney disease (PKD) is a common cause of end-stage renal failure, for which there is no accepted treatment. Progenitor and stem cells have been shown to restore renal function in a model of renovascular disease, a disease that shares many features with PKD. The objective of this study was to examine the potential of adult stem cells to restore renal structure and function in PKD. Bone marrow-derived mesenchymal stromal cells (MSCs, 2.5 × 10(5)) were intrarenally infused in 6-week-old PCK rats. At 10 weeks of age, PCK rats had an increase in systolic blood pressure (SBP) versus controls (126.22 ± 2.74 vs. 116.45 ± 3.53 mmHg, p < 0.05) and decreased creatinine clearance (3.76 ± 0.31 vs. 6.10 ± 0.48 µl/min/g, p < 0.01), which were improved in PKD animals that received MSCs (SBP: 114.67 ± 1.34 mmHg, and creatinine clearance: 4.82 ± 0.24 µl/min/g, p = 0.001 and p = 0.003 vs. PKD, respectively). MSCs preserved vascular density and glomeruli diameter, measured using microcomputed tomography. PCK animals had increased urine osmolality (843.9 ± 54.95 vs. 605.6 ± 45.34 mOsm, p < 0.01 vs. control), which was improved after MSC infusion and not different from control (723.75 ± 56.6 mOsm, p = 0.13 vs. control). Furthermore, MSCs reduced fibrosis and preserved the expression of proangiogenic molecules, while cyst size and number were unaltered by MSCs. Delivery of exogenous MSCs improved vascular density and renal function in PCK animals, and the benefit was observed up to 4 weeks after a single infusion. Cell-based therapy constitutes a novel approach in PKD.
多囊肾病（PKD）是终末期肾衰竭的常见病因，目前尚无公认的治疗方法。在肾血管疾病模型中，祖细胞和干细胞已被证明可恢复肾功能，肾血管疾病与PKD有许多共同特征。本研究的目的是检测成体干细胞在PKD中恢复肾脏结构和功能的潜力。将骨髓来源的间充质基质细胞（MSCs，2.5×10⁵个）经肾内注入6周龄的PCK大鼠体内。10周龄时，PCK大鼠的收缩压（SBP）较对照组升高（126.22±2.74 vs. 116.45±3.53 mmHg，p<0.05），肌酐清除率降低（3.76±0.31 vs. 6.10±0.48 μl/min/g，p<0.01），而接受MSCs的PKD动物上述指标得到改善（SBP：114.67±1.34 mmHg，肌酐清除率：4.82±0.24 μl/min/g，与PKD组相比，p分别为0.001和0.003）。使用微型计算机断层扫描测量发现，MSCs可维持血管密度和肾小球直径。PCK动物的尿渗透压升高（843.9±54.95 vs. 605.6±45.34 mOsm，与对照组相比，p<0.01），在注入MSCs后得到改善，且与对照组无差异（723.75±56.6 mOsm，与对照组相比，p=0.13）。此外，MSCs可减少纤维化并维持促血管生成分子的表达，而囊肿大小和数量未因MSCs而改变。外源性MSCs的注入改善了PCK动物的血管密度和肾功能，且在单次注入后长达4周都观察到了这种益处。基于细胞的治疗构成了PKD的一种新方法。
