S139 JUNCTIONAL ADHESION MOLECULE A (JAM-A) IS A CRITICAL REGULATOR OF HSC HOMING AND MAINTENANCE OF STEM CELL QUIESCENCE

• DOI: 10.1097/01.hs9.0000558776.86374.3f
• Publication Date: 2019-06-17T13:52:53Z
• Authors: B. Cao; C. Hart; S. Iberl; G. Müller; B. Williams; S. Heazlewood; M. Domingues; A. Vinson; X. Sun; S. Li; C. Heazlewood; C. Pritchard; D. Haylock; C. Nefzger; J. Polo; R. Schelker; W. Herr; I. Martin-Padura; J. Grassinger; S. Nilsson
• Keywords: Homing (biology); Hematopoietic stem cell; Mobilization

Background: The success of clinical hematopoietic stem cell (HSC) transplants is highly dependent on the ability HSC to home bone marrow (BM). Although it appreciated that recovery post-transplant correlated infused number, greater understanding homing mechanisms should allow us identify improved transplant strategies are not solely reliant number but also quality. Mobilized blood most common source for and gold standard mobilization agent, granulocyte-colony stimulating factor (G-CSF), known impair HSC. G-CSF-mobilization be associated with reduced expression key adhesion molecules we hypothesize this include junctional molecule A (JAM-A), a transmembrane protein enriched long-term Currently, specific role JAM-A in mobilization, maintenance known. Aims: To assess (JAM-A) engraftment as well BM. In addition, aim G-CSF independent strategy does reduce receptors, thus providing mobilized product enhanced capacity. Methods: Anti-JAM-A antibody treatment followed by into either C57BL/6 or NSG mice were used murine human HSC, respectively. Mice injected anti-JAM-A blocking 3 consecutive days determine whether prolonged inhibition vivo leads alteration small combination α4β1/α9β1 integrin antagonist “BOP” CXCR4 “AMD3100” cells comparatively assessed using 1) single RNAseq 2) flow cytometric analysis molecules, including JAM-A, CXCR4, α4β1 α9β1 3) transplantation. Results: has multi-faceted roles regulation during steady state following mobilization. Specifically, critical contributes preferential quiescence endosteal niche (region closely bone/BM interface). Furthermore, significantly reduces result cleavage tumor necrosis α-converting enzyme, which upregulated administration. have impaired potential, attributed lower levels integrins compared BOP AMD3100. Consequently, show injection plus AMD3100 1 hour was capable mobilizing progenitors multi-lineage potential 4-day approach. Summary/Conclusion: Our results regulator progenitor trafficking BM suggests use (e.g. AMD3100) do abrogate function transplants.