VLA-4 Agonist Promote Engraftment and Cell Immune Reconstitution of Allogeneic Hematopoietic Stem Cells

However, little is known about how to promote implantation and early immune reconstitution of HSCs through regulating its own functions. Here, we identified very-late antigen (VLA-4) as a pivotal target in regulating HSC implantation.

Critically, we screened out a VLA-4 agonist, which could promote the implantation and long-term hematopoietic reconstitution of donor HSCs in a mixed donor chimerism (MDC) mouse model and serial xenotransplantation model of human CD34+ cells from umbilical cord blood (UCB). Competitive transplantation mouse model and limited dilution assay for UCB CD34+ cells revealed that VLA-4 agonist could enhance the self-renewal capacity of HSCs and increase the number of severe combined immunodeficient (SCID)-repopulating cells (SRCs) to five-fold in vivo.