Tubular cell-enriched subpopulation of primary renal cells improves survival and augments kidney function in rodent model of chronic kidney disease
Tubular cell-enriched subpopulation of primary renal cells improves survival and augments kidney function in rodent model of chronic kidney disease
复制标题
DOI：
10.1152/ajprenal.00221.2010
复制
发表时间：
2010-11-01
影响因子：
4.2
通讯作者：
Presnell, Sharon C.
中科院分区：
文献类型：
--
作者：
Kelley, Rusty;Werdin, Eric S.;Presnell, Sharon C.
Kelley R, Werdin ES, Bruce AT, Choudhury S, Wallace SM, Ilagan RM, Cox BR, tatsumi - fight P, Rivera EA, Spencer T, Rapoport HS, Wagner BJ, Guthrie K, Jayo MJ, Bertram TA, Presnell SC.原发性肾细胞亚群对慢性肾脏疾病小鼠生存和肾功能的影响。[J] .中国生物医学工程学报，2016,31(2):444 - 444。首次发表于2010年9月8日；doi: 10.1152 / ajprenal.00221.2010。慢性肾脏疾病（CKD）可以通过肾滤过严重受损来确定，最终导致需要透析或肾移植。透析只能解决CKD的一些后遗症，并且需要移植的患者与可用器官之间存在显着差距，这为新的CKD治疗方式的发展提供了动力。一些人认为CKD是由组织损伤与肾脏内在修复和再生过程之间的渐进式不平衡发展而来的。在这项研究中，我们通过两步5/6肾减体积术（NX）建立CKD后4-7周，通过原位肝实质内注射给鼠肾细胞，通过生理、组织和分子标记评估了肾细胞对肾脏功能和结构再生的影响。该模型、细胞传递和系统效应的概念证明是通过异质肾细胞群（unx）进行的，该细胞群包含来自肾脏所有主要隔室的细胞。众所周知，肾小管细胞是急性损伤后原位肾再生的贡献者。最初作为对照测试，富管细胞的亚群（B2）令人惊讶地优于UNFX。两项独立研究（持续时间3个月和6个月）证实，B2可显著延长生存期，改善肾滤过（血清肌酐和血尿素氮）。通过与无细胞对照和同等剂量的非B2细胞的直接比较，证实了B2效应的特异性。治疗后6个月肾脏定量组织学评估证实B2治疗减轻了肾脏组织病理的严重程度。治疗相关的转化生长因子(TGF)- β 1、纤溶酶原激活物抑制剂(PAI)-1和纤维连接蛋白（FN）的减少证明B2细胞减弱了促纤维化细胞外基质生成的典型途径。
Kelley R, Werdin ES, Bruce AT, Choudhury S, Wallace SM, Ilagan RM, Cox BR, Tatsumi-Ficht P, Rivera EA, Spencer T, Rapoport HS, Wagner BJ, Guthrie K, Jayo MJ, Bertram TA, Presnell SC. Tubular cell-enriched subpopulation of primary renal cells improves survival and augments kidney function in rodent model of chronic kidney disease. Am J Physiol Renal Physiol 299: F1026-F1039, 2010. First published September 8, 2010; doi:10.1152/ajprenal.00221.2010.-Established chronic kidney disease (CKD) may be identified by severely impaired renal filtration that ultimately leads to the need for dialysis or kidney transplant. Dialysis addresses only some of the sequelae of CKD, and a significant gap persists between patients needing transplant and available organs, providing impetus for development of new CKD treatment modalities. Some postulate that CKD develops from a progressive imbalance between tissue damage and the kidney's intrinsic repair and regeneration processes. In this study we evaluated the effect of kidney cells, delivered orthotopically by intraparenchymal injection to rodents 4-7 wk after CKD was established by two-step 5/6 renal mass reduction (NX), on the regeneration of kidney function and architecture as assessed by physiological, tissue, and molecular markers. A proof of concept for the model, cell delivery, and systemic effect was demonstrated with a heterogeneous population of renal cells (UNFX) that contained cells from all major compartments of the kidney. Tubular cells are known contributors to kidney regeneration in situ following acute injury. Initially tested as a control, a tubular cell-enriched subpopulation of UNFX (B2) surprisingly outperformed UNFX. Two independent studies (3 and 6 mo in duration) with B2 confirmed that B2 significantly extended survival and improved renal filtration (serum creatinine and blood urea nitrogen). The specificity of B2 effects was verified by direct comparison to cell-free vehicle controls and an equivalent dose of non-B2 cells. Quantitative histological evaluation of kidneys at 6 mo after treatment confirmed that B2 treatment reduced severity of kidney tissue pathology. Treatment-associated reduction of transforming growth factor (TGF)-beta 1, plasminogen activator inhibitor (PAI)-1, and fibronectin (FN) provided evidence that B2 cells attenuated canonical pathways of profibrotic extracellular matrix production.