Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.
Potential Use of Autologous Renal Cells from Diseased Kidneys for the Treatment of Renal Failure.
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DOI：
10.1371/journal.pone.0164997
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yoo JJ
中科院分区：
文献类型：
--
作者：
George SK;Abolbashari M;Jackson JD;Aboushwareb T;Atala A;Yoo JJ
慢性肾脏疾病(CKD)是指某些疾病导致肾脏逐渐丧失功能。对于慢性肾脏病患者，肾移植是恢复肾功能的唯一治疗选择。在这项研究中，我们评估了从病变肾脏获得的原代肾脏细胞，以确定它们的正常表型和功能特征是否被保留，并可用于细胞治疗。从正常肾脏(NK)和病变肾脏(CKD)分离的原代肾细胞具有相似的表型特征和生长动力学。肾小管细胞标记物水通道蛋白-1和E-钙粘附素以及足细胞特异性标记物WT-1和Nephin在NK和CKD肾来源细胞中的表达水平相似。用荧光激活细胞分选技术(FACS)鉴定出特殊的肾细胞群，包括近端肾小管细胞(83.1%来自NK和80.3%来自CKD肾脏)、远端肾小管细胞(11.03%来自NK和10.9%来自CKD肾脏)和足细胞(1.91%来自NK和1.78%来自CKD肾脏)。扫描电子显微镜超微结构分析显示，NK和CKD培养细胞的顶端表面均有微绒毛。此外，透射电子显微镜(TEM)分析显示，紧密连接、桥粒和其他细胞内结构类似。NK和CKD来源的肾细胞对Na+的摄取特性也相似(分别为24.4mmoL/L和25mmoL/L)，两种细胞对蛋白质的摄取和转运特性没有显著差异。这些结果表明，来自CKD等疾病肾脏的原代肾细胞在体外培养时具有与来自正常健康肾脏(NK)的细胞相似的结构和功能特征。这项研究表明，来自病变肾脏的细胞可能被用作肾脏细胞治疗的自体细胞来源，特别是在CKD或终末期肾脏疾病(ESRD)患者中。
Chronic kidney disease (CKD) occurs when certain conditions cause the kidneys to gradually lose function. For patients with CKD, renal transplantation is the only treatment option that restores kidney function. In this study, we evaluated primary renal cells obtained from diseased kidneys to determine whether their normal phenotypic and functional characteristics are retained, and could be used for cell therapy. Primary renal cells isolated from both normal kidneys (NK) and diseased kidneys (CKD) showed similar phenotypic characteristics and growth kinetics. The expression levels of renal tubular cell markers, Aquaporin-1 and E-Cadherin, and podocyte-specific markers, WT-1 and Nephrin, were similar in both NK and CKD kidney derived cells. Using fluorescence- activated cell sorting (FACS), specific renal cell populations were identified and included proximal tubular cells (83.1% from NK and 80.3% from CKD kidneys); distal tubular cells (11.03% from NK and 10.9% from CKD kidneys); and podocytes (1.91% from NK and 1.78% from CKD kidneys). Ultra-structural analysis using scanning electron microscopy (SEM) revealed microvilli on the apical surface of cultured cells from NK and CKD samples. Moreover, transmission electron microscopy (TEM) analysis showed a similar organization of tight junctions, desmosomes, and other intracellular structures. The Na+ uptake characteristics of NK and CKD derived renal cells were also similar (24.4 mmol/L and 25 mmol/L, respectively) and no significant differences were observed in the protein uptake and transport characteristics of these two cell isolates. These results show that primary renal cells derived from diseased kidneys such as CKD have similar structural and functional characteristics to their counterparts from a normal healthy kidney (NK) when grown in vitro. This study suggests that cells derived from diseased kidney may be used as an autologous cell source for renal cell therapy, particularly in patients with CKD or end-stage renal disease (ESRD).
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