Spleen route accelerates engraftment of human hematopoietic stem cells

Intravenous injections of human hematopoietic stem cells (hHSCs) is routinely used in clinic and for modeling hematopoiesis in mice. However, unspecific dilution in vascular system and non-hematopoietic organs challenges engraftment efficiency. Although spleen is capable of extra medullar hematopoiesis, its ability to support human HSC transplantation has never been evaluated. We demonstrate that intra-splenic injection results in high and sustained engraftment of hHSCs into immune-deficient mice, with higher chimerisms than with intravenous or intra-femoral injections. Our results support that spleen microenvironment provides a niche for HSCs amplification and offers a new route for efficient HSC transplantation. •Intra-splenic (IS) route allows high engraftment of human HSC into immune deficient mice.•IS route is more efficient than intravenous (IV) route.•Limiting dilutions showed that IS-SRCs were 3-fold higher numerous than IV-SRCs.•Spleen microenvironment provides a niche for HSCs amplification.