Renal Autologous Cell Therapy to Stabilize Function in Diabetes-Related Chronic Kidney Disease: Corroboration of Mechanistic Action With Cell Marker Analysis

Stavas, Joseph M.; Filler, Guido; Jain, Deepak; Ludlow, John W.; Basu, Joydeep; Payne, Richard; Butler, Emily; Ferris, Maria; Bertram, Tim

doi:10.1016/j.ekir.2022.04.014

Cited by 8 publications

(14 citation statements)

References 49 publications

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“…Two cellular fractions are selected and combined to form rat SRCs, which comprise primarily renal epithelial cells, including podocytes ( 7 – 12 ). Extensive non-clinical evidence corroborated by emerging clinical data support the notion that orthotopic implantation of SRCs are reparative and restorative ( 8 – 10 , 12 , 13 ). In the ZSF1 rat model of DKD ( 12 ), intervention with SRCs improved survival and mitigated loss of renal structure and function.…”

Section: Discussionmentioning

confidence: 77%

“…SRCs, a renal epithelial cell-enriched platform, are being advanced as autologous cell-based therapy for the treatment of CKD ( 13 ). In the present study, we report that the gene products of cdh1 , cubn , nphs1 , epo , kdr , hes1 , and pecam1 , mRNA differentially expressed by SRCs ( 10 ), reside within the tubular and glomerular compartments.…”

Section: Discussionmentioning

confidence: 99%

“…Advantages of such an approach include reduced risks for alloimmune events, bioincompatibility, and disease transmission (6). Autologous selected renal cell (SRC) therapy involves 10.3389/fmed.2022.1062890 use of biopsy-sourced kidney cells that are expanded in culture, submitted to gradient separation followed by implantation of a select fraction into the donor's kidney (7)(8)(9)(10)(11)(12)(13). Phenotypelabeling studies suggest that SRCs are composed primarily of renal epithelial cells, including podocytes (7)(8)(9)(10)(11)(12)(13), a finding consistent with the source of SRCs, viz.…”

Section: Introductionmentioning

confidence: 99%

“…Autologous selected renal cell (SRC) therapy involves use of biopsy-sourced kidney cells that are expanded in culture, submitted to gradient separation followed by implantation of a select fraction into the donor’s kidney ( 7 – 13 ). Phenotype-labeling studies suggest that SRCs are composed primarily of renal epithelial cells, including podocytes ( 7 – 13 ), a finding consistent with the source of SRCs, viz. the renal cortex.…”

Section: Introductionmentioning

confidence: 99%

“…Consistent with these observations, non-clinical data indicate that administration of SRCs to diseased kidneys stimulates a reparative response and improvement in renal filtration ( 8 – 10 , 12 ). Evaluation of glomerular filtration rate in a subset of diabetic kidney disease (DKD) patients at increased risk for ESRD suggests that randomization to SRCs (REACT™) is associated with stabilization of renal function ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

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Selected renal cells harbor nephrogenic potential

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Selected renal cells harbor nephrogenic potential

et al. 2022

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Advances and potential of regenerative medicine in pediatric nephrology

et al. 2023

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The endogenous capacity of the kidney to repair is limited, and generation of new nephrons after injury for adequate function recovery remains a need. Discovery of factors that promote the endogenous regenerative capacity of the injured kidney or generation of transplantable kidney tissue represent promising therapeutic strategies. While several encouraging results are obtained after administration of stem or progenitor cells, stem cell secretome, or extracellular vesicles in experimental kidney injury models, very little data exist in the clinical setting to make conclusions about their efficacy. In this review, we provide an overview of the cutting-edge knowledge on kidney regeneration, including pre-clinical methodologies used to elucidate regenerative pathways and describe the perspectives of regenerative medicine for kidney patients.

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