Refining the migration and engraftment of short-term and long-term HSCs by enhancing homing-specific adhesion mechanisms

Asma S. Al-Amoodi, Yanyan Li, Arwa Al-Ghuneim, Hanaa Allehaibi, Ioannis Isaioglou, Luke E. Esau, Dina B. AbuSamra, Jasmeen S. Merzaban*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


In contrast to the short-term (ST) CD341 stem cells, studies have suggested that long-term (LT) hematopoietic stem cells (HSCs) found in the CD342 stem cell pool have trouble migrating and engrafting when introduced through IV. To understand why these deficiencies exist, we set out to fully elucidate the adhesion mechanisms used by ST and LT-HSCs to migrate to the bone marrow(BM). Specifically focusing on murine ST-HSCs (Flk22CD341) and LT-HSCs (Flk22CD342), we observed a distinctive expression pattern of BM homing effectors necessary for the first step, namely sialyl Lewis-X (sLex) (ligand for E-selectin), and the second step, namely CXCR4 chemokine receptor (receptor for SDF-1). sLex expression was higher on Flk22CD341 ST-HSCs (.60%) compared with Flk22CD342 LT-HSCs (,10%), which correlated to binding to E-selectin. Higher concentrations of CXCR4 were observed on Flk22CD341 ST-HSCs compared with Flk22CD342 LT-HSCs. Interestingly, the expression of CD26, a peptidase known to deactivate chemokines (ie, SDF-1), was higher on Flk22CD342 LT-HSCs. Given that both E-selectin–binding and CXCR4-mediated migration are compromised in Flk22CD342 LT-HSCs, we aimed to enhance their ability to migrate using recombinant human fucosyltransferase 6 (rhFTVI) and the CD26 inhibitor, Dip A (diprotin A). To this end, we observed that although LT-HSCs expressed low concentrations of sLex, they were able to engraft when transplanted into recipient mice. Moreover, although both CD26 inhibition and fucosylation enhanced migration of both HSC populations in vitro, only pretreatment of LT-HSCs with Dip A enhanced engraftment in vivo after transplantation into recipient mice. Remarkably, fucosylation of Flk22CD341 ST-HSCs consistently led to their ability to transplant secondary recipients. These data suggest that using fucosylation and Dip A to overcome the molecular disparity in adhesion mechanisms among ST-HSCs and LT-HSCs differentially influences their abilities to migrate and engraft in vivo and promotes the ability of ST-HSCs to engraft secondary recipient mice, the gold standard for testing functionality of LT-HSCs.

Original languageEnglish (US)
Pages (from-to)4373-4391
Number of pages19
JournalBlood advances
Issue number15
StatePublished - Aug 9 2022

ASJC Scopus subject areas

  • Hematology


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