An in vivo humanized model to study homing and sequestration of Plasmodium falciparum transmission stages in the bone marrow

Abstract

IntroductionRecent evidence suggests that the bone marrow (BM) plays a key role in the diffusion of P. falciparum malaria by providing a “niche” for the maturation of the parasite gametocytes, responsible for human-to-mosquito transmission. Suitable humanized in vivo models to study the mechanisms of the interplay between the parasite and the human BM components are still missing.MethodsWe report a novel experimental system based on the infusion of immature P. falciparum gametocytes into immunocompromised mice carrying chimeric ectopic ossicles whose stromal and bone compartments derive from human osteoprogenitor cells.ResultsWe demonstrate that immature gametocytes home within minutes to the ossicles and reach the extravascular regions, where they are retained in contact with different human BM stromal cell types.DiscussionOur model represents a powerful tool to study BM function and the interplay essential for parasite transmission in P. falciparum malaria and can be extended to study other infections in which the human BM plays a role.

Modeling skeletal dysplasia in Hurler syndrome using patient-derived bone marrow osteoprogenitor cells

“…In this study, we used patient-derived models for reproducing and elucidating the cartilage pathology in MPS IH using skeletal progenitor cells. We applied these models to provide insight into the biological and transcriptional changes that are associated with endochondral ossification dysfunction in MPS IH patients, offering the first evidence to our knowledge that cartilaginous pellets and heterotopic ossicles, already employed in studies on hematological malignancies and infectious diseases ( 19 , 20 ), could be used to reproduce the skeletal pathology features of an inherited disease.…”