Article Impact Level: HIGH Data Quality: STRONG Summary of Stem Cell Reports https://doi.org/10.1016/j.stemcr.2025.102640 Dr. Toshiya Nishimura et al.
Points
- An international research team developed the AR medium to optimize culture conditions and manipulate signaling pathways essential for maintaining the pluripotency of canine induced pluripotent stem cells.
- The study identified that fibroblast growth factor, transforming growth factor-beta, and WNT signals are critical components for the robust maintenance and stabilization of these specific stem cell lines.
- Cells cultured in this optimized medium demonstrated a homogenized global gene expression pattern that allowed for the successful establishment of NANOG-reporter canine induced pluripotent stem cell lines.
- The protocol facilitated the differentiation of stem cells into cardiomyocytes that exhibited functional rhythmic contractions and structural sarcomere alignment identical to native heart muscle tissue.
- This methodological advancement supports the use of canine models for testing drug safety and investigating genetic treatments for shared human and animal conditions like dilated cardiomyopathy.
Summary
This study addresses the persistent challenge of maintaining pluripotency and directing differentiation in canine induced pluripotent stem cells (ciPSCs), a technology currently limited by a lack of robust, species-specific protocols. An international team utilized a newly developed culture formulation, designated as AR medium, to manipulate critical signaling pathways including fibroblast growth factor (FGF), activin/transforming growth factor (TGF)-β, and WNT signals. The objective was to establish a stable environment for NANOG-reporter ciPSC lines that facilitates both the maintenance of the undifferentiated state and the subsequent controlled differentiation into specific tissue types.
Analysis of the ciPSCs cultured in the optimized AR medium demonstrated a homogenized global gene expression pattern, overcoming the instability and spontaneous differentiation often observed with traditional media. Following the stabilization of the undifferentiated state, the protocol successfully directed the cells to differentiate into functional cardiomyocytes. These derived cells exhibited specific genetic and protein markers exclusive to heart muscle, including successful sarcomere alignment. Crucially, the cardiomyocytes displayed rhythmic, spontaneous contractions, confirming their functional identity with native cardiac tissue.
The findings establish the AR medium as a viable tool for generating functional canine cardiomyocytes for translational research. By producing cells that are functionally identical to heart muscle, this protocol enables high-fidelity preclinical testing for drug efficacy and safety, particularly for conditions with shared genetic pathways in humans and dogs, such as dilated cardiomyopathy. This development suggests a scalable platform for accelerating regenerative medicine applications and investigating molecular treatments for complex hepatic, neurological, and cardiovascular disorders.
Link to the article: https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(25)00244-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2213671125002449%3Fshowall%3Dtrue
References
Nishimura, T., Kimura, K., Igarashi, K. J., Shishida, K., Sugisaki, H., Tsukamoto, M., Balakumar, A., Funamoto, C., Hirabayashi, M., Kol, A., & Hatoya, S. (2025). Signaling pathway-based culture condition improves differentiation potential of canine induced pluripotent stem cells. Stem Cell Reports, 20(10), 102640. https://doi.org/10.1016/j.stemcr.2025.102640
