BioE Seminar: Tissue Engineering with Skin Somatic Stem Cells
Thursday, April 19, 2018
12:00 pm - 1:00 pm
Fitzpatrick Center Schiciano Auditorium Side B, room 1466
Xiaoyang, Wu, Ph.D., Assistant Professor, The Ben May Department for Cancer Research, The University of Chicago
Somatic gene therapy provides a promising therapeutic approach for treatment of a variety of otherwise terminal or severely disabling diseases. The recent development of genome editing technology, including CRISPR (clustered regularly-interspaced short palindromic repeats) system, has made it possible to perform precise genetic engineering in cells. However, clinical application of CRISPR technology to human patients has been challenging due to the inadequate efficacy in vivo using conventional delivery approach. Thus, it is urgently needed to develop an ex vivo platform that can combine both precise genome editing in vitro with effective application of engineered cells in vivo.
The epidermal progenitor cells of skin have several unique advantages, making it particularly suited for ex vivo gene therapy. Human skin is the largest and most accessible organ in the body, making it easy to isolate skin epidermal progenitor cells and monitor the tissue for potential detrimental complications. Anatomically, skin epidermis is separated from vasculature by the basement membrane, which prevents potential dissemination of genetically modified cell in vivo, making the potential therapy tissue specific and safe. Lastly, the potential applicability of cutaneous gene therapy is broad because it has been well documented that proteins expressed in skin epidermal cells can cross the epidermal/dermal barrier and reach circulation to achieve therapeutic effect in a systematic manner. In addition, ectopic expression of metabolic enzymes in skin epidermal cells can transform the engineered skin into a “metabolic sink” for correction of various metabolic disorders. However, despite the potential clinical importance, research in epidermal progenitor cell-based therapy (cutaneous gene therapy) has been greatly hindered due to lack of an appropriate mouse model. Although mouse or human skin can be transplanted to immunodeficient mice, lack of an intact immune system makes it impossible to examine the potential outcomes and complications that the therapy may elicit in vivo. We have now resolved the technical hurdle and established a unique mouse-to-mouse skin transplantation model that can stably introduce genome-edited epidermal progenitor cells into immunocompetent mice. Our study demonstrated the broad applicability of engineered skin grafts for treatment of different diseases.
Xiaoyang Wu’s research interests include somatic stem cells in skin. The skin epidermis and its appendages provide a protective barrier that keeps harmful microbes out and essential body fluids in. To perform these functions while confronting the harsh physicochemical traumas from the outside world, our skin must undergo rejuvenation through homeostasis and wound repair. Both processes rely on the activities of skin stem cells, including the activation and migration of stem cells upon wounding and the delicate balance of stem cell proliferation, self-renewal, and differentiation during tissue homeostasis. Understanding the underlying mechanisms is particularly important, as these processes, when gone awry, lead to skin diseases including cancers.
Wu was the first author for a number of publications, including “Focal Adhesion Kinase Regulation of N-WASP Subcellular Localization and Function” and “ACF7 Regulates Cytoskeletal–Focal Adhesion Dynamics and Cell Migration and Has ATPase Activity.” Most recently, he received the Cancer Research Foundation Young Investigator Award and an American Cancer Society Institutional Research Grant.
Wu was awarded his PhD in pharmacology from Cornell University in 2006. He also received biochemistry degrees from Nanjing University, China (MS in 2000 and BS in 1997). Wu joined the University of Chicago faculty in 2012.