Bone marrow stromal cell transplantation ameliorates cytopenias caused by depletion of FAP-α expressing cells
Camarillo Retamosa, Eva
MetadataShow full item record
This item's downloads: 251 (view details)
Mesenchymal stromal cell (MSC) therapies are being successfully developed for immune-mediated inflammatory diseases as phase 3 clinical trials have demonstrated. However, the en-dogenous roles of stromal cells (SSCs) are not fully elucidated. Fibroblast activation protein-α (FAP) is a marker of tissue resident SSCs removable in FAPDM2 mice using diphtheria toxin (DT) receptor-mediated conditional cell knockout (TRECK). Two DT doses confirmed FAP-α+ cell ablation at 72h associated with anaemia and altered haematopoiesis. Our hypothesis relies on the administration of a single intravenous (i.v) dose of stromal cells 24h after DT exposure alleviates the phenotypes associated with FAP-α+ cell depletion and attributed them to FAP-α+ SSCs. Peripheral blood (PB) counts and flow cytometry tests on haematopoietic and stromal cell (HSC & SSC) populations in BM were examined post ablation and MSC administration. FAP-α+ cell ablation resulted in anaemia, thrombocytopenia and neutropenia in PB and general hypo-cellularity was observed in BM, specifi-cally, megakaryocytes progenitors (MEP) but increased multipotent progenitors (MPP2). In addi-tion to FAP-α+ SSCs, other stromal cell subsets decreased; namely PDFGR-α, Leptin-R, gp38, and SDC2. Administration (i.v) of a single MSC (2.5x105) dose expressing FAP-α+ rescued anaemia, ame-liorated thrombocytopenia and neutropenia in PB as well as improved the cellularity of the mar-row: specifically progenitors (Lin-Sca-1+) and MEP, whereas the percentage of MPP2 was reversed indicating the lineage biased of the MPP2 to erytrocytosis and megakaryocytosis. FAP-α+ SSCs are necessary for marrow homeostasis and a single dose of BM-MSCs is sufficient to restore anaemia, alleviate thrombocytopenia and neutropenia and increase the haematopoietic progenitor’s absolute numbers in BM.
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. Please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.
The following license files are associated with this item: