Open AccessHigh‐efficient generation of VCAM‐1 + mesenchymal stem cells with multidimensional superiorities in signatures and efficacy on aplastic anaemia mice
Author(s) -
Wei Yimeng,
Zhang Leisheng,
Chi Ying,
Ren Xiang,
Gao Yuchen,
Song Baoquan,
Li Chengwen,
Han Zhibo,
Zhang Lei,
Han Zhongchao
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12862
Subject(s) - mesenchymal stem cell , immunophenotyping , biology , haematopoiesis , stem cell , regenerative medicine , transplantation , cancer research , matrigel , aplastic anemia , immunology , bone marrow , medicine , microbiology and biotechnology , flow cytometry , angiogenesis
Abstract 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‐1β, IL‐4 with IFN‐γ, 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.