Living Biomaterials to Engineer Hematopoietic Stem Cell Niches

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, living biomaterials based on Lactococcus lactis to control hematopoietic stem cells in 2D surfaces and 3D hydrogels are introduced. L. lactis is 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. These 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 (HSPCs)-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 suggest the possibility of using living materials based on genetically engineered bacteria for the ex-vivo expansion of HSPC with eventual practical clinical applications in HSPCs transplantation for hematological disorders.

Automated summary

Living biointerfaces are a new type of biomaterials that combine living cells and polymeric matrices to act as instructive materials for surrounding cells. In this study, living biomaterials based on Lactococcus lactis expressing specific genes were used to control hematopoietic stem cells in both 2D and 3D environments. The results showed that these living biomaterials can direct the interaction between stem cells and bacteria, and can significantly expand the population of specific stem cells in 3D hydrogels. The findings suggest the potential of using genetically engineered bacteria-based living materials for ex-vivo expansion of stem cells and clinical applications in hematological disorders.