Project description:Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 (KRT9) expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency. Given fibroblasts' capacity to modify keratinocyte differentiation, we hypothesized that volar fibroblasts influence these features. Bioprinted skin constructs confirmed the capacity of volar fibroblasts to induce volar keratinocyte features. A clinical trial of healthy volunteers demonstrated that injecting volar fibroblasts into nonvolar skin increased volar features that lasted up to 5 months, highlighting a potential cellular therapy.
Project description: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
Project description: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
Project description: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
Project description: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
