Japanese researchers claim world’s first ‘footprint-free’ cat stem cells

Researchers at Osaka Metropolitan University have announced the generation of the world’s first high-quality, “footprint-free” feline induced pluripotent stem cells (fiPSCs). Publishing their research in Regenerative Therapy, the scientists created novel stem cells that are free from residual reprogramming genes. In other words, no trace of the genetic manipulation used to create them remains. These footprint-free stem cells thus offer a safer and potentially more effective approach for developing future therapies.

Potential for feline and human disease

This development opens new avenues for studying and treating chronic diseases prevalent in cats, such as kidney disease and diabetes. But the potential benefits of the research may not be constrained to felines alone. Because cats share a complex living environment and develop diseases similar to people, these fiPSCs hold promise as models for human diseases as well.

In the scope of research, the scientists derived the iPSCs from feline uterine cells collected during routine sterilization procedures as well as from feline embryonic fibroblasts. According to the paper, the team also successfully derived iPSCs from feline embryonic fibroblasts. A Sendai virus vector delivered six feline-specific transcription factors (Oct3/4, Sox2, Klf4, c-Myc, NANOG, and LIN28A), ensuring the resulting iPSCs were free of exogenous genetic material. This non-integrating method overcomes limitations of previous feline iPSC generation techniques.

Confirming fiPSCs’ pluripotency

Under the leadership of Shingo Hatoya of the Graduate School of Veterinary Science, the research team confirmed the fiPSCs’ pluripotency — their ability to differentiate into any cell type in the body. The cells exhibited key characteristics, including expressing specific stem cell markers and forming teratomas (benign tumors containing tissues from all three germ layers) when transplanted into mice. This technique demonstrated their capacity for trilineage differentiation, a hallmark of true pluripotency. The paper also notes that the fiPSCs maintained normal karyotypes over extended passages, an important indicator of genetic stability.

In addition, the team reported a significant advance in cell culture methodology. Unlike previous attempts, these fiPSCs can be maintained under feeder-free and chemically defined conditions, eliminating the need for animal-derived products in the culture medium. Specifically, the paper mentions the use of StemFit AK02N medium and iMatrix-511 for maintaining the cells. Consequently, this reduces contamination risks and improves the consistency of results.

Potential in chronic kidney disease and diabetes

Professor Hatoya highlighted the need for this research, stating in a press release, “Especially in cats, chronic kidney disease and diabetes are serious problems. Establishing a method to direct these cells to form kidney or pancreas tissue will be a challenge for future research.” The paper emphasizes that these conditions in cats can serve as models for similar human diseases, underlining the translational potential of this research.

Looking ahead, the team emphasized the broader implications of their work. “We anticipate providing these high-quality feline iPSCs to researchers worldwide,” Professor Hatoya explained. “They can be utilized in veterinary regenerative medicine research, understanding the underlying mechanisms of genetic diseases, and developing new therapeutic agents.”