We propose a method of in vivo tissue repair based on the modulation of cell microenvironment via the application of specific growth factor/chemical combinations to harness adult cell differentiation. This enables a targeted method for site-specific cell reprogramming for in vivo tissue regeneration after pathological loss of tissue matrix. This research is unique in that it employs adult cell plasticity, without genetic intervention. Our approach is, therefore, clinically applicable and readily achievable. In this proposal, we have outlined ex vivo studies and an in vivo proof of concept study which will provide the basis for the development of a treatment for corneal disease such as keratoconus, an ectatic corneal dystrophy of the eye. New Zealand has a high prevalence of keratoconus and the highest reported rate of corneal transplant surgery for keratoconus in the world. Although initially tested in the eye, this technology will be transferable across multiple health needs.