Centro Ricerca M. Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Monza, Italy.
School of Cancer and Pharmacological Sciences and KHP Cancer Research UK Centre, King's College London, London, UK.
Bone Marrow Transplant. 2022 Jun;57(6):942-948. doi: 10.1038/s41409-022-01662-1. Epub 2022 Apr 8.
The improvement of hematopoietic stem and progenitor cell (HSPC) engraftment remains a high-priority goal when limited cell doses are available, such as in cord blood (CB) transplantation and HSC gene therapy. We observed that monocytes are highly effective at improving the engraftment of both CB-CD34 and lentivirus-transfected CD34 cells in a xenogeneic model of HSC transplantation. Moreover, monocytes, in particular the CD14CD16 classical subset, in co-culture systems increase survival and stemness of CB-CD34 cells. Both soluble factors and direct-cell contact interactions, such as JAG/NOTCH and COX-2/PGE2 pathways, are critically involved in the HSC-monocyte crosstalk. Our results indicate that the infusion of monocytes improves engraftment when cell dose is a limiting factor.
当细胞剂量有限时，如在脐带血（CB）移植和 HSC 基因治疗中，提高造血干细胞和祖细胞（HSPC）的植入仍然是一个首要目标。我们观察到单核细胞在异种造血干细胞移植模型中非常有效地提高 CB-CD34 和慢病毒转染的 CD34 细胞的植入。此外，单核细胞，特别是 CD14CD16 经典亚群，在共培养系统中增加 CB-CD34 细胞的存活和干性。可溶性因子和直接细胞接触相互作用，如 JAG/NOTCH 和 COX-2/PGE2 途径，都在 HSC-单核细胞相互作用中起着关键作用。我们的结果表明，当细胞剂量成为限制因素时，输注单核细胞可提高植入。
