Direct bone marrow HSC transplantation enhances local engraftment at the expense of systemic engraftment in NSG mice

Futrega, Kathryn, Lott, William B., & Doran, Michael R. (2016) Direct bone marrow HSC transplantation enhances local engraftment at the expense of systemic engraftment in NSG mice. Scientific Reports, 6, Article Number-23886.

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Direct bone marrow (BM) injection has been proposed as a strategy to bypass homing inefficiencies associated with intravenous (IV) hematopoietic stem cell (HSC) transplantation. Despite physical delivery into the BM cavity, many donor cells are rapidly redistributed by vascular perfusion, perhaps compromising efficacy. Anchoring donor cells to 3-dimensional (3D) multicellular spheroids, formed from mesenchymal stem/stromal cells (MSC) might improve direct BM transplantation. To test this hypothesis, relevant combinations of human umbilical cord blood-derived CD34(+) cells and BM-derived MSC were transplanted into NOD/SCID gamma (NSG) mice using either IV or intrafemoral (IF) routes. IF transplantation resulted in higher human CD45(+) and CD34(+) cell engraftment within injected femurs relative to distal femurs regardless of cell combination, but did not improve overall CD45(+) engraftment at 8 weeks. Analysis within individual mice revealed that despite engraftment reaching near saturation within the injected femur, engraftment at distal hematopoietic sites including peripheral blood, spleen and non-injected femur, could be poor. Our data suggest that the retention of human HSC within the BM following direct BM injection enhances local chimerism at the expense of systemic chimerism in this xenogeneic model.

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ID Code: 94974
Item Type: Journal Article
Refereed: Yes
Keywords: Haemopoetic Stem Cells, Bone marrow, engraftment
DOI: 10.1038/srep23886
ISSN: 2045-2322
Divisions: Current > Schools > School of Biomedical Sciences
Current > Schools > School of Chemistry, Physics & Mechanical Engineering
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Facilities: Science and Engineering Centre
Copyright Owner: Copyright 2016
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Deposited On: 19 Apr 2016 04:39
Last Modified: 19 Apr 2016 23:10

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