Ectopic humanized mesenchymal niche in mice enables robust engraftment of myelodysplastic stem cells
Authors listSyed Mian Ander Abarrategi Kar Lok Kong Kevin Rouault-Pierre Henry Wood Caroline Anna Oedekoven Alexander E Smith Antoniana Batsivari Linda Ariza-Mcnaughton Peter Johnson Thomas Snoeks Ghulam J Mufti Dominique Bonnet
Myelodysplastic syndrome (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SCs) in mice by implantation of human mesenchymal cell-seeded scaffolds. Critically for modelling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 10 CD34 cells can be engrafted and expanded by this approach with the maintenance of the genetic make-up seen in the patients. Non-invasive high-resolution ultrasound imaging shows that these scaffolds are fully perfused. Our data shows that human microenvironment but not mouse is essential to MDS-SCs homing and engraftment. Notably, the alternative niche provided by healthy donor MSCs enhanced engraftment of MDS-SCs. This study characterizes a new tool to model MDS human disease with the level of engraftment previously unattainable in mice, and offers insights into human-specific determinants of MDS-SC microenvironment.
Journal Blood Cancer Discovery
Issue number 2