Bacteriophage-based biomaterials for manipulating derivation and differentiation of human induced pluripotent stem cells

Abstract

Induced pluripotent stem cells (iPSCs), which are derived from somatic cells, can differentiate into any cell type. They are promising tools in medical applications including regenerative medicine, personalized cell therapy, disease modeling, and drug discovery. The current stem cell research faces at least the following two major challenges: how to improve the reprogramming efficiency in iPSCs derivation; and how to control the differentiation of stem cells into certain cell types. The works in this dissertation attempt to find solutions to tackle the above two challenges. To enhance the reprogramming efficiency of somatic cells into iPSCs, human dermal fibroblasts (HDFs)-internalizing peptides were selected using Phage Display Peptide Library. After the selection, 3 HDF-binding peptides with high occurrences were selected for further screening. Finally, the HDF-binding peptide with the strongest affinity and high specificity was chemically conjugated to the surface of a nanoparticle plasmid carrier to improve the endocytosis efficiency and further help with the reprogramming process. To induce directional differentiation of iPSCs or iPSC-derived stem cells, a novel 2D virus-based substrate with unique self-assembled hierarchical nano- and micro-topographies was developed. This substrate can direct the bidirectional differentiation of iPSC-derived neural progenitor cells (NPCs) into neurons and astrocytes without the use of costly growth factors, which also provide a new approach for studying the interaction between neurons and astrocytes.