Living biomaterials to engineer hematopoietic stem cell niches

Abstract

Living biointerfaces are a new class of biomaterials combining living cells and polymeric matrices that can act as biologically active and instructive materials that host and provide signals to surrounding cells. Here we introduce living biomaterials based on Lactococcus lactis to control hematopoietic stem cells in 2D surfaces and 3D hydrogels. L. lactis has been modified to express C-X-C motif chemokine ligand 12 (CXCL12), thrombopoietin (TPO), vascular cell adhesion protein 1 (VCAM1) and the 7th-10th type III domains of human plasma fibronectin (FN III7-10), in an attempt to mimic ex vivo the conditions of the human bone marrow Our results suggest that living biomaterials that incorporate bacteria expressing recombinant CXCL12, TPO, VCAM1 and FN in both 2D systems direct hematopoietic stem and progenitor cells (HSPC)-bacteria interaction, and in 3D using hydrogels functionalized with full-length human plasma fibronectin allow for a notable expansion of the CD34+/CD38–/CD90+ HSPC population compared to the initial population. These results provide a strong evidence based on data that suggests the possibility of using living materials based on genetically engineered bacteria for the ex-vivo expansion of HSPC with eventual practical clinical applications in HSPC transplantation for hematological disorders.