줄기세포 표현형 제어를 위한 세포 친화적인 고분자 생체재료

Abstract

In tissue engineering approaches, polymeric scaffolds play a critical role in the construction of biomimetic microenvironments, as they provide the mechanical stability and present binding sites for cell adhesion. Polymer scaffolds can regulate stem cell differentiation into various lineages by modification with various bioactive molecules. Controlling cell-matrix interactions as well as cell-cell interactions is important for regulating stem cell phenotype, such as adhesion, proliferation, and differentiation in tissue engineering. Alginate hydrogels modified with RGD peptides containing various spacer arm lengths increased osteogenic and adipogenic differentiation of D1 stem cells, as the spacer arm length increased. On the contrary, chondrogenic differentiation was independent of the spacer arm length at the same cell concentration. However, as the cell concentration increased, adhesion ligand with long spacer arm was able to improve the chondrogenic differentiation of D1 stem cells. Cell-cell interactions were also very important for chondrogenic differentiation of the stem cells. LRP5 peptide, known to bind to N-cadherin was chemically introduced to alginate gels and the gels were useful to enhance chondrogenic differentiation of D1 stem cells even at the low cell density, compared to RGD-modified alginate gels. Controlling cell-cell interactions in polymeric scaffolds was also critical in creation hematopoietic stem cell (HSC) niche in vitro. Stem cell niche is a specific microenvironment where stem cells are located, and in which stem cells maintain their quiescence and pluripotency. Angiopoietin-1 (Ang-1) coupled to alginate gels were able to bind to tyrosine kinase receptor (Tie2) on the surface of HSCs. Ang1-modified alginate gels provided a niche for HSC quiescence, compared with those co-cultured with osteoblasts. Development of cell-instructive polymeric materials for controlling stem cell phenotype may find useful applications in tissue engineering as well as in cell transplantation using stem cells.