Pluripotent stem cells can grow in culture indefinitely and differentiate into all cell types of the body, two properties that are very attractive for regenerative medicine. These stem cells can either be isolated from embryos (embryonic stem cells) or they can be generated by reprogramming adult cells back into a pluripotent state (induced pluripotent stem cells or IPSC). IPSC from a variety of wild, agricultural, and companion animals, such as the Tasmanian devil, cow, horse, and dog have been created and well-characterized. In contrast, little research has been done on IPSC generated from feline cells.

Two years ago, the PI took a sabbatical leave to learn how to create and characterize IPSC in the bovine system. With this experience, we propose to expand this technique in our lab to create feline IPSC. These cells will be used for studies focused on the potential of feline IPSC in regenerative medicine, and will provide a novel platform for other Cornell researchers interested in treating and/or modeling diseases important to feline health (e.g., cancer, heart diseases, infectious diseases).

In Aim 1, we will create feline IPSC by reprogramming feline fetal fibroblasts, using 2 approaches. One approach, based on published literature, uses a traditional retroviral-based reprogramming system, whereas the other approach will use a more recently developed Sendai virus-based reprogramming system. The cells will then be characterized both phenotypically and functionally to confirm their pluripotent nature. In Aim 2, we will differentiate feline IPSC into functional mesenchymal stromal cells (MSC), characterize the IPSC-derived MSC, and use them in our well-established in vitro assays to assess their regenerative and antimicrobial properties.

The overall importance and significance of this proposal is that it will provide a source of well-characterized feline pluripotent stem cells that can be used by our group and others interested in feline health, leading to improved therapeutic interventions and increased knowledge on disease pathogenesis.