Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia

被引：59

作者：

Huo, Jiali ^{[1
]}

Zhang, Leisheng ^{[1
,2
]}

Ren, Xiang ^{[1
]}

Li, Chengwen ^{[1
]}

Li, Xingxin ^{[1
]}

Dong, Peiyuan ^{[1
]}

Zheng, Xuan ^{[1
]}

Huang, Jinbo ^{[1
]}

Shao, Yingqi ^{[1
]}

Ge, Meili ^{[1
]}

Zhang, Jing ^{[1
]}

Wang, Min ^{[1
]}

Nie, Neng ^{[1
]}

Jin, Peng ^{[1
]}

Zheng, Yizhou ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, State Key Lab Expt Hematol, 288 Nanjing Rd, Tianjin 300020, Peoples R China

[2] Nankai Univ, Sch Med, Postdoctoral Res Stn, Tianjin 300071, Peoples R China

来源：

STEM CELL RESEARCH & THERAPY | 2020年 / 11卷 / 01期

基金：

中国博士后科学基金; 中国国家自然科学基金;

关键词：

Acquired aplastic anemia; MSCs; Biological phenotype; Genetic alterations; Immunodysregulation; BONE-MARROW-TRANSPLANTATION; STEM-CELLS; PATHOPHYSIOLOGY; CYCLOSPORINE;

D O I：

10.1186/s13287-020-1577-2

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Background Longitudinal studies have verified the pivotal role of mesenchymal stem/stromal cells (MSCs) in the bone marrow microenvironment for hematopoiesis and coordinate contribution to leukemia pathogenesis. However, the precise characteristics and alternation of MSCs during acquired aplastic anemia (AA) remain obscure. Methods In this study, we originally collected samples from both healthy donors (HD) and AA patients to dissect the hematological changes. To systematically evaluate the biological defects of AA-derived MSCs (AA-MSCs), we analyzed alterations in cellular morphology, immunophenotype, multi-lineage differentiation, cell migration, cellular apoptosis, and chromosome karyocyte, together with the immunosuppressive effect on the activation and differentiation of lymphocytes. With the aid of whole genome sequencing and bioinformatic analysis, we try to compare the differences between AA-MSCs and HD-derived MSCs (HD-MSCs) upon the molecular genetics, especially the immune-associated gene expression pattern. In addition, the efficacy of umbilical cord-derived MSC (UC-MSC) transplantation on AA mice was evaluated by utilizing survivorship curve, histologic sections, and blood cell analyses. Results In coincidence with the current reports, AA patients showed abnormal subsets of lymphocytes and higher contents of proinflammatory cytokines. Although with similar immunophenotype and chromosome karyotype to HD-MSCs, AA-MSCs showed distinguishable morphology and multiple distinct characteristics including genetic properties. In addition, the immunosuppressive effect on lymphocytes was significantly impaired in AA-MSCs. What is more, the cardinal symptoms of AA mice were largely rescued by systemic transplantation of UC-MSCs. Conclusions Herein, we systematically investigated the signatures and efficacy of MSCs to dissect the alterations occurred in AA both at the cellular and molecular levels. Different from HD-MSCs, AA-MSCs exhibited multifaceted defects in biological characteristics and alterative molecular genetics in the whole genome. Our findings have provided systematic and overwhelming new evidence for the defects of AA-MSCs, together with effectiveness assessments of UC-MSCs on AA as well.

引用

页数：18