Infusion of endothelial progenitor cells accelerates hematopoietic and immune reconstitution, and ameliorates the graft-versus-host disease after hematopoietic stem cell transplantation.
Hematopoietic stem cells transplantation (HSCT) causes endothelial cell damage, disrupting hematopoietic microenviroment and leading to various complications. We hypothesized that infusion of endothelial progenitor cells (EPCs) may improve endothelium repair, facilitate hematopoietic reconstitution, and alleviate complications associated with HSCT. C57Bl6, and BALB/c mice received total body irradiation followed by infusion of C57Bl6-derived bone marrow (BM) cells, with or without concomitant infusion of C57Bl6-derived EPCs. The time course of hematopoietic and immune reconstitution and the severity of the graft-versus-host disease (GVHD) were monitored. Further, to confirm that EPCs promote endothelial cell recovery, HSCT mice were treated with anti-VE-cadherin antibody targeting the endothelium. The EPCs-treated mice exhibited accelerated recovery of BM vasculature, cellularity, hematopoietic stem and progenitor cell recovery, improved counts of lymphocyte subsets in peripheral blood, and facilitated spleen structure reconstruction. EPCs infusion also ameliorated the GVHD in the C57Bl6 → BALB/c allo-HSCT model. Systemic administration of anti-VE-cadherin antibody significantly delayed hematological and immune reconstitution in the EPCs-infused mice. In conclusion, our data demonstrate that infusion of EPCs augments the hematopoietic and immune reconstitution, and alleviates the GVHD. These findings further highlight the relationship between the microvascular recovery, hematopoietic and immune reconstitution, and the GVHD.
Department of Hematology, The Affiliated Hospital of Xuzhou Medical College, No. 99 West Huaihai Road, Xuzhou 221002, Jiangsu, China.
Lingyu
L
Zeng
Chong
C
Chen
Guoliang
G
Song
Zhiling
Z
Yan
Shijuan
S
Xu
Lu
L
Jia
Shuang
S
Ding
Jiang
J
Cao
Wei
W
Chen
Hai
H
Cheng
Zhenyu
Z
Li
Wei
W
Sang
Lin
L
Wang
Youping
Y
Li
Kailin
K
Xu
D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D042783:Endothelial Cells / Q000166:cytology* / Q000473:pathology; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D020127:Recovery of Function; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D014184:Transplantation, Homologous / Q000009:adverse effects