Karissa T. Chabner

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During mammalian ontogeny, haematopoietic stem cells (HSCs) translocate from the fetal liver to the bone marrow, where haematopoiesis occurs throughout adulthood. Unique features of bone that contribute to a microenvironmental niche for stem cells might include the known high concentration of calcium ions at the HSC-enriched endosteal surface. Cells respond(More)
The specialized microenvironment or niche where stem cells reside provides regulatory input governing stem cell function. We tested the hypothesis that targeting the niche might improve stem cell-based therapies using three mouse models that are relevant to clinical uses of hematopoietic stem (HS) cells. We and others previously identified the osteoblast as(More)
Biocompatible inorganic matrices have been used to enhance bone repair by integrating with endogenous bone architecture. Hypothesizing that a three-dimensional framework might support reconstruction of other tissues as well, we assessed the capacity of a tantalum-coated carbon matrix to support reconstitution of functioning thymic tissue. We engineered a(More)
Haematopoietic stem and progenitor cells (HSPCs) change location during development and circulate in mammals throughout life, moving into and out of the bloodstream to engage bone marrow niches in sequential steps of homing, engraftment and retention. Here we show that HSPC engraftment of bone marrow in fetal development is dependent on the(More)
T-lymphocyte depletion of bone marrow grafts compromises engraftment, suggesting a facilitating mechanism provided by the T cells that has been shown to associate with CD8(+) but not CD4(+) T cells. Explanations for this phenomenon have focused on immune targeting of residual host cells or cytokine production. We provide evidence for an alternative(More)
It has recently been reported that in a xenotransplantation model of human cells injected into nonobese diabetic–severe combined immunodeficient mice, direct intratibial injection of stem cells improves engraftment.1,2 However, the complexities of using this approach clinically are substantial. We sought to determine whether in a syngeneic mouse model the(More)
Hematopoietic stem/progenitor cells (HSPC) transition in location during development1 and circulate in mammals throughout life2, moving into and out of the bloodstream to engage bone marrow (BM) niches in sequential steps of homing, engraftment and retention3–5. We show here that HSPC engraftment of BM in fetal development is dependent upon the guanine(More)
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