Endothelium-targeted Human Delta-like 1 Enhances the Regeneration and Homing of Human Cord Blood Stem and Progenitor Cells

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2016 Jan 8

PMID 26740017

Citations 6

Authors

Deng-Mei Tian

Ying-Min Liang

Yong-Qing Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Umbilical cord blood (UCB) is becoming an alternative cell source for hematopoietic stem cell transplantation (HSCT). However, umbilical cord blood transplantation (UCBT) has been severely limited by low and finite numbers of hematopoietic stem cells and their delayed engraftment. New strategies are needed to improve ex vivo expansion efficiency and in vivo haematopoietic recovery.

Methods: We produced an endothelium-targeted soluble Notch ligand, the Delta-Serrate-Lag-2 (DSL) domain of human Delta-like 1 fused with a RGD motif (hD1R), and tested the effects of this protein on human umbilical cord blood hematopoietic stem and progenitor cell (UCB-HSPC) ex vivo and in vivo.

Results: hD1R-mediated ex vivo expansion system was able to significantly increase the absolute number of UCB-HSPCs. The hD1R-expanded cells had the enhanced homing and maintained long-term hematopoietic stem cell repopulation capacity in the bone marrow of immunodeficient nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice. Moreover, systemic administration of hD1R promoted the in vivo regeneration of donor cells in recipient mice and accelerated hematopoietic recovery, particularly in settings wherein the HSPCs dose was limiting.

Conclusions: Our results indicated that hD1R might be applied in improving hematopoietic recovery and HSC engraftment in human UCBT.

Citing Articles

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Hematopoietic Stem Cell Niche During Homeostasis, Malignancy, and Bone Marrow Transplantation.

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[Effect of endothelial cell-targeted soluble Notch ligand hD1R protein on the proliferation of acute myeloid leukemia cells].

Tian D, Liang Y, Zhang Y Zhonghua Xue Ye Xue Za Zhi. 2018; 39(10):845-850.

PMID: 30369206 PMC: 7348280. DOI: 10.3760/cma.j.issn.0253-2727.2018.10.011.

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