Dental Pulp Stem Cell-Derived Extracellular Vesicles Mitigate Haematopoietic Damage after Radiation
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Dental Pulp Stem Cell-Derived Extracellular Vesicles Mitigate Haematopoietic Damage after Radiation Fanxuan Kong 1,2 Hua Wang 1,3
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Chu-Tse Wu 1,3 & Panpan Geng 1 & Chao Liu 4
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Fengjun Xiao 1,3
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Li-Sheng Wang 1,3 &
# The Author(s) 2020
Abstract Radiation therapy can cause haematopoietic damage, and mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) have been shown to reverse this damage. Our previous research showed that dental pulp stem cells (DPSCs) have a strong proliferation capacity and can produce abundant amounts of EVs to meet the requirements for use in vitro and in vivo. DPSCs derived EVs (DPSCs-EVs) are evaluated for their effect on reducing haematopoietic damage. Haematopoietic stem cell (HSC) numbers and function were assessed by flow cytometry, peripheral blood cell counts, histology and bone marrow transplantation. Epidermal growth factor (EGF) was used as a reference for evaluating the efficiency of EVs. miRNA microarray was employed to find out the changes of miRNA expression after cells being irradiated in vivo and the role they may play in mitigation the radiation caused injury. We observed the effect of DPSCs-EVs on promoting proliferation and inhibiting apoptosis of human umbilical vein endothelial cells (HUVECs) and FDC-P1 cells in vitro. We found that DPSCs-EVs and EGF could comparably inhibit the decrease in WBC, CFU count and KSL cells in vivo. We also verified that EVs could accelerate the recovery of long-term HSCs. In summary, DPSCs-EVs showed an apoptosis resistant effect on HUVECs and FDC-P1 cells after radiation injury in vitro. EVs from DPSCs were comparable to EGF in their ability to regulate haematopoietic regeneration after radiation injury in vivo. Radiation could alter the expression of some miRNAs in bone marrow cells, and EVs could correct these changes to some extent.
Keywords Extracellular vesicles . Radiation injuries . Haematopoietic stem cells . Dental pulp stem cells . microRNA Abbreviations BMSC bone marrow stromal cell CAR CXCL12-abundant reticular CFU colony forming unit
DPSC EC EGF EV
dental pulp stem cell endothelial cell epidermal growth factor extracellular vesicle
This article is part of the Topical Collection on Special Issue on Exosomes and Microvesicles: from Stem Cell Biology to Translation in Human Diseases Guest Editor: Giovanni Camussi Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12015-020-10020-x) contains supplementary material, which is available to authorized users. * Hua Wang [email protected]; [email protected] Chu-Tse Wu [email protected]
2
PLA Strategic Support Force Characteristic Medical Center, No.9 An-Xiang-Bei-Li, Chao-Yang District, Beijing 100101, People’s Republic of China
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Beijing Key Laboratory for Radiobiology, No.27 Tai-ping Road, Hai-Dian District, Beijing 100850, People’s Republic of China
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Binzhou Medical University, No.522 Huang-He-Third-Road, Yantai 264003, People’s Republic of China
Li-Sheng Wang [email protected] 1
Department of Experimental H
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