On June 7th, Dr. Lian from Penn State University visited BEBC and gave a talk entitled "Human Stem Cell Engineering: Directed Differentiation and Tissue Engineering".

Dr. Lian is an expert for stem cell differentiation, especially to cardiomyocytes. 

The following is an abstract of his speech: Human pluripotent stem cells (hPSCs) offer tremendous promise in tissue engineering and cell-based therapies because of their unique combination of two properties: pluripotency and virtually unlimited proliferative potential. Hurdles facing utilization of hPSCs in cardiovascular regenerative medicine include a lack of reliable and efficient methods to differentiate hPSCs to cardiovascular lineages.

Here we show that differentiation stage-specific modulation of canonical Wnt signaling is both essential and sufficient for efficient endothelial and heart muscle cells induction from hPSCs under chemically defined conditions. First, we report a robust method to efficiently produce endothelial cells from hPSCs via glycogen synthase kinase 3 (Gsk3) inhibition and culture in defined media to direct hPSC differentiation to endothelial progenitors which were multipotent, capable of differentiating into calponin-expressing smooth muscle cells and endothelial cells. Next, we report sequential treatment of hPSCs with Gsk3 inhibitors followed by inducible expression of β-catenin shRNA or chemical inhibitors of Wnt signaling produced a high yield of virtually (up to 98%) pure functional human cardiomyocytes. Last, we report the large scale synchronization, generation, and purification of human ventricular muscle progenitors. Using the RNA-seq and bioinformatic analyses, we identified cell-surface markers for Isl1+ ventricular progenitors. Furthermore, we developed a novel strategy to perform in vivo tissue engineering using these purified Isl1+ progenitors and generated centimeter long vascularized human ventricular tissues in murine kidneys. In addition, in vivo intramyocardial transplantation of purified human Isl1+ ventricular progenitors results in their spontaneous migration and assembly into multi-cellular pure muscular patch of mature ventricular muscle cells. Our studies suggest the clinical feasibility of generate new heart parts via organ-on-organ level tissue engineering with large scale, purified populations of committed heart progenitors from hPSCs.