Bioengineering of humanized bone marrow microenvironments in mouse and their visualization by live imaging
journal contributionposted on 15.10.2020, 16:12 by Diana Passaro, Ander Abarrategi, Katie Foster, Linda Ariza-McNaughton, Dominique Bonnet
Human hematopoietic stem cells (HSCs) reside in the bone marrow (BM) niche, an intricate, multifactorial network of components producing cytokines, growth factors, and extracellular matrix. The ability of HSCs to remain quiescent, self-renew or differentiate, and acquire mutations and become malignant depends upon the complex interactions they establish with different stromal components. To observe the crosstalk between human HSCs and the human BM niche in physiological and pathological conditions, we designed a protocol to ectopically model and image a humanized BM niche in immunodeficient mice. We show that the use of different cellular components allows for the formation of humanized structures and the opportunity to sustain long-term human hematopoietic engraftment. Using two-photon microscopy, we can live-image these structures in situ at the single-cell resolution, providing a powerful new tool for the functional characterization of the human BM microenvironment and its role in regulating normal and malignant hematopoiesis.
AnimalsBioengineeringBone MarrowBone Marrow CellsBone Morphogenetic Protein 2CollagenFemaleHematopoietic Stem Cell TransplantationHematopoietic Stem CellsHumansMaleMice, SCIDMicroscopy, Fluorescence, MultiphotonOptical ImagingStem Cell NicheTissue ScaffoldsBonnet FC001045BRF-ackHP-ack1702 Cognitive Sciences0601 Biochemistry and Cell Biology1701 Psychology