Wound Healing and Tissue Repair
Novel Method for Inducing Tissue Repair
The healing of open wounds or replacement of lost tissue following injury, reconstructive surgery, transplantation or loss of blood supply requires the formation of new blood vessels as well as the growth of organized tissue. At present there are no reproducible procedures to speed up tissue growth, which requires formation of extracellular matrix and collagens by activated fibroblasts, and to induce new blood vessel formation. Recombinant tissue growth factors have been utilized for this purpose with limited success due to their short half-life in vivo, limited penetration into deeper tissue regions, and difficulty in application directly to naturally healing tissue.
Wistar scientists have constructed replication-defective recombinant adenoviruses which express platelet-derived growth factor B (PDGF-B), vascular endothelial growth factor (VEGF) as well as other growth factors. Clinical trials of these vectors to enhance wound healing in diabetic ulcers have been planned; additional applications of the technology, including the use of the vectors in tissue engineering are in development.
Method of Producing a Stem Cell-Like Melanocyte
Wistar scientists have invented a method of producing a dedifferentiated melanocyte, a premelanoma stem cell-like cell, by activating specific intracellular targets and selecting for a stem cell-like melanocyte capable of proliferating under stem cell growth conditions. These dedifferentiated melanocytes increase expression of neural crest-related genes and exhibit a decrease in pigmentation-related genes, compared to untreated controls. Stem cell-like melanocytes are capable of further differentiation into various cell types, assuming neuronal, smooth muscle cell, oligodendrocyte, melanocyte, or chondrocyte phenotypes. Wistar scientists have defined an oncogenic role for Notch signaling in melanocytes and highlight the potential for Notch inhibition to be used as a therapeutic approach for the treatment of melanoma.
Multipotent Adult Stem Cells from Human Hair Follicles
Scientists at The Wistar Institute and the University of Pennsylvania have developed a novel strategy for isolating, growing, and differentiating broadly multipotent adult stem cells from human hair follicles. Adult stem cells, like embryonic stem cells, can differentiate into multiple types of function-dedicated daughter cells, such as nerve or muscle cells. However, most adult stem cells are restricted to producing cell types from only one tissue type (lineage). Researchers at Wistar, in collaboration with researchers at the University of Pennsylvania isolated a unique adult stem cell from human hair follicles, which is capable of producing daughter cells of multiple tissue lineages. The human hair follicle stem cell is a rare, but permanent, inhabitant of the skin follicular microenvironment, and exhibits features that are characteristic of highly-adaptable embryonic stem cells. This technology allows hair follicle stem cells to be collected, maintained in renewable culture, and stimulated to produce daughter cells of multiple classes, including functional skin cells, muscle cells, and nerve cells.