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Identification of functional pathways for regenerative bioactivity of selected renal cells
Wei Sha1, Timothy Bertram2, Deepak Jain2
1Bioinformatics Services Division, Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 150 Research Campus Drive, Ste. 3333, Kannapolis, NC, 28081, USA.
Background:
Selected 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.
Methods:
A comparative bioinformatic analysis of transcripts specifically enriched or depleted in SRC component sub-populations relative to the initial, biopsy-derived cell source was conducted.
Results:
Outcomes 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.
Conclusions:
These 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.
Insights
Selected renal cells (SRC) show regenerative potential for chronic kidney disease (CKD). Transcriptomic analysis reveals SRC leverage kidney development pathways for therapeutic bioactivity, offering insights into CKD treatment mechanisms.
Area of Science:
- Nephrology
- Regenerative Medicine
- Bioinformatics
Background:
- Selected renal cells (SRC) are an autologous cell therapy in Phase II trials for chronic kidney disease (CKD).
- Preclinical studies in rodent models demonstrated SRC's ability to modulate renal biomarkers relevant to CKD progression.
Purpose of the Study:
- To conduct a comparative bioinformatic analysis of transcriptomic changes in SRC.
- To identify key transcriptomic networks and signaling pathways involved in SRC's therapeutic bioactivity for CKD.
Main Methods:
- Genome-wide transcriptomic profiling of rodent SRC.
- Comparative bioinformatic analysis of SRC sub-populations versus the original cell source.
Main Results:
- Identification of therapeutically relevant bioactivity in SRC.
- Key transcriptomic networks and pathways linked to SRC's reparative, restorative, and regenerative effects in rodent CKD models were identified.
- These include genes and networks involved in cell cycle, transcriptional control, inflammation, ECM-receptor interaction, immune response, actin polymerization, regeneration, cell adhesion, and morphogenesis.
Conclusions:
- SRC regenerative bioactivity utilizes gene networks associated with kidney development.
- These findings provide evidence for potential mechanisms of action for SRC in treating chronic kidney disease.
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