Artificial Red Blood Cells Generated From Canine Stem Cells

Blood transfusions are crucial in human and veterinary medicine, yet human blood reserves are in constant need of donors while blood bank systems in veterinary care are nearly non-existent. This leaves canine transfusions largely reliant on donations from healthy dogs, but securing compatible blood remains a major challenge since dogs also have different blood types.

Fortunately, recent advances in induced pluripotent stem cells (iPSCs) have created new opportunities for producing blood cells in the laboratory. This and the similarities between human and canine health have drawn attention to dogs as translational models that can be used to bring about innovative changes in both fields. However, a method for generating red blood cells from canine iPSCs has not been fully established.

Taking on this crucial challenge, a research group led by Professor Shingo Hatoya at Osaka Metropolitan University’s Graduate School of Veterinary Science used canine iPSCs developed through collaborative research with TOKIWA-Bio Inc. to devise a method for generating red blood cell-like cells. Mimicking the natural process of blood cell development, canine iPSCs were cultured as cell clusters and then induced to develop into red blood cell-like cells. Progenitor cells, the origin of blood cells, emerged during culturing and yielded cells containing hemoglobin, the oxygen-carrying protein found in red blood cells.

Furthermore, using CRISPR-Cas9 genome editing to target glycophorin A (GYPA), a red blood cell marker, the researchers created canine iPSCs that glow green when GYPA is expressed. This allowed the team to visualize and track red blood cell differentiation in real time. Under the optimized differentiation conditions, more than 96% of the analyzed cells expressed GYPA.

“The cells generated in this study are not yet fully mature red blood cells suitable for transfusion,” said Professor Hatoya. “Only about 3% of the cells underwent enucleation, a key feature of mature mammalian red blood cells. Future studies will focus on improving the generation of functional red blood cells and understanding differences among cell lines.”

While this study does not yet provide transfusion-ready red blood cells, it establishes an important platform for generating red blood cell-like cells from canine iPSCs. The findings may also contribute to the development and evaluation of iPSC-derived blood products for human medicine.