期刊
CELL PROLIFERATION
卷 53, 期 8, 页码 -出版社
WILEY
DOI: 10.1111/cpr.12862
关键词
Aplastic anaemia; genetic alteration; hUC-MSCs; immunoregulation; proangiogenesis; VCAM-1
类别
资金
- Science and Technology Project of Tianjin [17ZXSCSY00030]
- China Postdoctoral Science Foundation [2019M661033, JCQY012]
- Nanyang Science and Technology Project of He-nan Province [JCQY012]
- CAMS Innovation Fund for Medical Sciences [2016-I2M-1-017]
- Natural Science Foundation of Tianjin City [19JCQNJC12500]
- CAMS Key Laboratory of Gene Therapy for Blood Diseases [2017PT31047, 2018PT31038, 2018PT32028]
- Beijing-Tianjin-Hebei Basic Research Project [18JCZDJC44600, H2018206423]
- Department of Science and Technology of Shangrao City
- Department of Science and Technology of Jiangxi Province
- Natural Science Foundation of Tianjin [19JCQNJC12500]
- National Natural Science Foundation of China [81330015, 81700119, 81900126]
Objective Longitudinal studies have indicated VCAM-1(+)mesenchymal stem/stromal cells (MSCs) as promising resources in regenerative medicine, yet the abundance in gene expression is far from adequate in the advantaged and discarded hUC-MSCs. Thus, high-efficient preparation and systematic dissection of the signatures and biofunctions of the subpopulation is the prerequisite for large-scale clinical applications. Materials and methods We primarily took advantage of a cytokine-based programming strategy for large-scale VCAM-1(+)hUC-MSC generation (III-MSCs). Thereafter, we conducted multifaceted analyses including cytomorphology, immunophenotype, cell vitality, multilineage differentiation, whole-genome analysis, tube formation and Matrigel plug assay, lymphocyte activation and differentiation, and systemic transplantation for aplastic anaemia (AA) treatment. Results III-MSCs with high-proportioned VCAM-1 expression were obtained by combining IL-1 beta, IL-4 with IFN-gamma, which exhibited comparable immunophenotype with untreated hUC-MSCs (NT-MSCs) but revealed multidimensional superiorities both at the cellular and molecular levels. Simultaneously, systemic infusion of III-MSCs could significantly ameliorate clinicopathological features and finally help facilitate haematopoietic reconstruction and immunoregulation in AA mice. Conclusions We have established a high-efficient procedure for large-scale generation of III-MSCs with preferable signatures and efficacy upon aplastic anaemia in mice. Our findings suggested that III-MSCs were advantageous sources with multifaceted characteristics for regenerative medicine.
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