Canine-Derived Vitronectin Developed for Stem Cell Culture Without Human Components

Canine induced pluripotent stem cells (ciPSCs) are valuable tools in veterinary regenerative medicine and disease modeling. When cultivating these cells, a culture substrate is required to provide a scaffold for attachment and growth. Without this support, the cells either die or lose their ability to differentiate.

Currently, recombinant proteins derived mainly from humans are used as substrates for culturing canine iPS cells. These human-based materials, however, are foreign to dog cells and may trigger immune rejection, limiting their suitability for clinical use. To overcome this limitation, a research group from Osaka Metropolitan University developed a species-specific approach.

The team engineered E. coli bacteria with canine genes that directed them to produce vitronectin (VTN). Acting as production systems, the E. coli generated sufficient quantities of VTN to function as a scaffold for canine iPS cell culture—eliminating the need for any human or mouse-derived materials. Testing showed that this dog-derived VTN supported cell growth and maintenance effectively, matching the performance of traditional human-derived vitronectin. The iPS cells also preserved their complete differentiation potential.

“This achievement is highly significant as it has paves the way for the stable cultivation of canine iPS cells without the use of human components,” explained Kohei Shishida, first author of the paper published in Regenerative Therapy. “This is valuable because it enables a fully canine culture system, reducing cross-species contamination risks.”

The researchers also examined a modified form of the protein, VTN-N, created by deleting part of its N-terminal region. The goal was to determine whether a simplified version could still maintain full functionality. The results showed that VTN-N performed comparably to human-derived vitronectin, maintaining adequate support for cell growth even with its reduced structure. The team expects that refining this version could improve the efficiency of large-scale production.

Senior author Professor Shingo Hatoya emphasized the broader implications: “This research brings the clinical application of regenerative medicine for intractable diseases commonly seen in dogs, such as heart disease, neurological disorders, and blood disorders, closer to reality.” “Canine-derived VTN can be produced stably and cost-effectively using E. coli, making it a useful foundational technology with broad applicability from research to clinical use.”