Biomimetic macroporous PEG hydrogels as 3D scaffolds for the multiplication of human hematopoietic stem and progenitor cells

Abstract

Multiplication of hematopoietic stem cells (HSCs) in vitro with current standard methods is limited and mostly insufficient for clinical applications of these cells. They quickly lose their multipotency in culture because of the fast onset of differentiation. In contrast, HSCs efficiently self-renew in their natural microenvironment (their niche) in the bone marrow. Therefore, engineering artificial bone marrow analogs is a promising biomaterial-based approach for culturing these cells. In the current study, a straight-forward, easy-to-use method for the production of biofunctionalized, macroporous hydrogel scaffolds that mimic the spongy architecture of trabecular bones was developed. As surrogates for cellular components of the niche, mesenchymal stem cells (MSCs) from different sources (bone marrow and umbilical cord) and osteoblast-like cells were tested. MSCs from bone marrow had the strongest pro-proliferative effect on freshly isolated human hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood. Co-culture in the pores of the three-dimensional hydrogel scaffold showed that the positive effect of MSCs on preservation of HSPC stemness was more pronounced in 3D than in standard 2D cell culture systems. Thus, the presented biomimetic scaffolds revealed to meet the basic requirements for creating artificial HSC niches.

Keywords: Biomimetic material; Bone marrow; Co-culture; HSC; HSPC; MSC; MSC-BM; MSC-UC; Stem cell; Stem cell niche; Three-dimensional scaffolds; hematopoietic stem and progenitor cell; hematopoietic stem cell; mesenchymal stem cell; mesenchymal stem cell from bone marrow; mesenchymal stem cell from umbilical cord.