Identification of functional pathways for regenerative bioactivity of selected renal cells

Stem Cell Research & Therapy

Wei Sha¹  Cory Brouwer¹  Joydeep Basu²  Deepak Jain²  Timothy Bertram² 

[1] Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 150 Research Campus Drive, Ste. 3333, 28081, Kannapolis, NC, USA;Prokidney, LLC, 27103, Winston-Salem, NC, USA;

关键词: Cell therapy;    Tissue engineering;    Chronic kidney disease;    Preclinical animal model;    Stem cell;    Transcriptomics;    Mechanism of action;    Selected renal cells;    Potency assay;   

DOI  :  10.1186/s13287-022-02713-6

来源: Springer

【 摘 要 】

BackgroundSelected renal cells (SRC) are in Phase II clinical trials as a kidney-sourced, autologous, tubular epithelial cell-enriched cell-based therapy for chronic kidney disease (CKD). In preclinical studies with rodent models of CKD, SRC have been shown to positively modulate key renal biomarkers associated with development of the chronic disease condition.MethodsA comparative bioinformatic analysis of transcripts specifically enriched or depleted in SRC component sub-populations relative to the initial, biopsy-derived cell source was conducted.ResultsOutcomes associated with therapeutically relevant bioactivity from a systematic, genome-wide transcriptomic profiling of rodent SRC are reported. Key transcriptomic networks and concomitant signaling pathways that may underlie SRC mechanism of action as manifested by reparative, restorative, and regenerative bioactivity in rodent models of chronic kidney disease are identified. These include genes and gene networks associated with cell cycle control, transcriptional control, inflammation, ECM–receptor interaction, immune response, actin polymerization, regeneration, cell adhesion, and morphogenesis.ConclusionsThese data indicate that gene networks associated with development of the kidney are also leveraged for SRC regenerative bioactivity, providing evidence of potential mechanisms of action.

【 授权许可】

CC BY