Development of Biomaterials for Feeder-Free and Xeno-Free Culture of Human Pluripotent Stem (Es and Ips) Cells(3/3)

Millions of people have suffered from damage of tissues and organs due to disease, accidents, or birthdefects. Pluripotent stem cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells(iPSCs) are an attractive prospect for tissue engineering and regenerative medicine. Human ESCs (hESCs)are attractive to use in clinical treatment due to differentiation ability into variety of somatic cells. However,there are ethical issues regarding use of human embryos for hESCs. Since 2007, these concerns can beovercome by induced pluripotent stem cells (iPSCs), if human iPSCs (hiPSCs) can be derived safely frompatients’ somatic cells and can culture under xeno-free conditions such as feeder-free conditions. Currently,hiPSCs and hESCs are cultured on mouse embryonic fibroblasts (MEFs) as a feeder layer. It is desirable togenerate and culture iPSCs and hESCs in xeno-free condition and especially feeder-free condition for clinicalusages. The tentative clinical potential of hiPSCs and hESCs is restricted by the use of MEFs as a feederlayer. This is because the possibility of xenogenic contamination during culture restricts the clinical use oftransplanted hiPSCs and hESCs. The development of feeder-free cultures using biomaterials havingoptimal elasticity and nanosegments as cell culture materials will create lower the cost of productionwithout introducing xenogenic contaminants and with more reproducible and reliable culture conditions.These improvements will open many avenues for potential stem cell-based regenerative therapies and thedevelopment of drug discovery platforms using hiPSCs and hESCs.The goal of this project, “Development of biomaterials for feeder-free and xeno-free culture of humanpluripotent stem (ES and iPS) cells”, is(a) Preparation of hydrogels (biomaterials) having different elasticity and specific nanosegments formaintenance of pluripotency of hiPSCs and hESCs on xeno-free and feeder free conditions,(b) Characterization of hiPSCs and hESCs cultured on the hydrogels having different elasticity andspecific nanosegments under feeder free conditions; Pluripotency of hiPSCs and hESCs, and differentiationefficiency into specific lineages (e.g., neural cells secreting dopamin for Parkinson disease treatment and betacells secreting insulin for diabate treatment).Crosslinked hydrogels showing different elasticity are selected as base cell culture materials. Severalbioactive oligopeptides and extracellular matrices (ECMs) are grafted on the hydrogel having differentelasticity. Furthermore, hiPSCs and hESCs on the hydrogels having different elasticity and nanosegments aredifferentiated into dopamin secreting cells (TH+ cells), insulin secreting cells (beta cells), osteoblasts, andcardiomyocytes. We will discuss the optimal nanosegments and nanosegments on the cell culture matrices formaintenance of pluripotency of hiPSCs and hESCs, and for differentiation of hiPSCs and hESCs in eachspecific lineage cells.