The use of ectopic volar fibroblasts to modify skin identity II
The modification of skin identity, such as the conversion of residual limb/stump (non-volar) skin of amputees to pressure-resistant palmoplantar skin to enhance prosthesis use and minimize skin breakdown, has tremendous clinical potential. Recognizing the capacity of fibroblasts to modify keratinocyte differentiation, we hypothesized that volar fibroblast injections might induce ectopic volar characteristics. First, we observed pressure-responsive volar fibroblast resulting in increased limb development after pressure treatment, then we confirmed this in using a bioprinted skin construct, and later in a clinical trial that showed increased volar measures in non-volar skin after volar fibroblast injections. Bulk and single cell RNA seq demonstrate gene ontology categories of cornified envelope, keratinization and morphogenic pathways. Thus, the long-term engraftment of volar fibroblasts creates a platform for the therapeutic development Overall design: Autologous scalp or sole fibroblasts were injected into the non-volar dermis with various doses (3.33 million or 10 million cells) or equivalent volume of media per injection at 3 visits spanning up to one week. A total of 10 million cells were injected. Skin biopsies from the injected sites were collected at 5-month post-injection time point. 136-26, 27, and28 received single dose of 10 million cells, while 136-43, 45, and 46 received three doses of 3.3 million cells.