Narayan Prakash, Bruce Andrew T, Rivera Elias A, Bertram Timothy A, Jain Deepak
Department of Bioprocess Research and Development, ProKidney LLC, Winston-Salem, NC, United States.
Front Med (Lausanne). 2022 Dec 22;9:1062890. doi: 10.3389/fmed.2022.1062890. eCollection 2022.
Selected renal cells (SRCs), a renal epithelial cell-enriched platform, are being advanced as an autologous cell-based therapy for the treatment of chronic kidney disease. However, the mechanism underlying its renal reparative and restorative effects remains to be fully elucidated. In this study, we coupled knowledgebase data with empirical findings to demonstrate that genes differentially expressed by SRCs form interactomes within tubules and glomeruli and mediate a suite of renal developmental activities including epithelial cell differentiation, renal vasculature development, and glomerular and nephron development. In culture, SRCs form organoids which self-assemble into tubules in the presence of a scaffold. Implanted into the kidneys of subtotally nephrectomized rats, SRCs are associated with comma- and S-shaped body cell formation and glomerular development, and improvement in renal filtration indices and renal microarchitecture. These data suggest that SRCs harbor nephrogenic potential, which may explain, at least in part, their therapeutic activity.
精选肾细胞(SRCs)是一种富含肾上皮细胞的平台,正作为一种基于自体细胞的疗法用于治疗慢性肾病。然而,其肾脏修复和恢复作用的潜在机制仍有待充分阐明。在本研究中,我们将知识库数据与实证结果相结合,以证明SRCs差异表达的基因在肾小管和肾小球内形成相互作用组,并介导一系列肾脏发育活动,包括上皮细胞分化、肾血管发育以及肾小球和肾单位发育。在培养过程中,SRCs形成类器官,在有支架的情况下可自组装成肾小管。将SRCs植入次全肾切除大鼠的肾脏后,其与逗号状和S形体细胞形成以及肾小球发育相关,并改善了肾滤过指标和肾脏微观结构。这些数据表明SRCs具有肾发生潜能,这可能至少部分解释了它们的治疗活性。