Cargando…
Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia
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 a...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020384/ https://www.ncbi.nlm.nih.gov/pubmed/32054519 http://dx.doi.org/10.1186/s13287-020-1577-2 |
_version_ | 1783497734144131072 |
---|---|
author | Huo, Jiali Zhang, Leisheng Ren, Xiang Li, Chengwen Li, Xingxin Dong, Peiyuan Zheng, Xuan Huang, Jinbo Shao, Yingqi Ge, Meili Zhang, Jing Wang, Min Nie, Neng Jin, Peng Zheng, Yizhou |
author_facet | Huo, Jiali Zhang, Leisheng Ren, Xiang Li, Chengwen Li, Xingxin Dong, Peiyuan Zheng, Xuan Huang, Jinbo Shao, Yingqi Ge, Meili Zhang, Jing Wang, Min Nie, Neng Jin, Peng Zheng, Yizhou |
author_sort | Huo, Jiali |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7020384 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-70203842020-02-20 Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia Huo, Jiali Zhang, Leisheng Ren, Xiang Li, Chengwen Li, Xingxin Dong, Peiyuan Zheng, Xuan Huang, Jinbo Shao, Yingqi Ge, Meili Zhang, Jing Wang, Min Nie, Neng Jin, Peng Zheng, Yizhou Stem Cell Res Ther Research 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. BioMed Central 2020-02-13 /pmc/articles/PMC7020384/ /pubmed/32054519 http://dx.doi.org/10.1186/s13287-020-1577-2 Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Huo, Jiali Zhang, Leisheng Ren, Xiang Li, Chengwen Li, Xingxin Dong, Peiyuan Zheng, Xuan Huang, Jinbo Shao, Yingqi Ge, Meili Zhang, Jing Wang, Min Nie, Neng Jin, Peng Zheng, Yizhou Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia |
title | Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia |
title_full | Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia |
title_fullStr | Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia |
title_full_unstemmed | Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia |
title_short | Multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia |
title_sort | multifaceted characterization of the signatures and efficacy of mesenchymal stem/stromal cells in acquired aplastic anemia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7020384/ https://www.ncbi.nlm.nih.gov/pubmed/32054519 http://dx.doi.org/10.1186/s13287-020-1577-2 |
work_keys_str_mv | AT huojiali multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT zhangleisheng multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT renxiang multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT lichengwen multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT lixingxin multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT dongpeiyuan multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT zhengxuan multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT huangjinbo multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT shaoyingqi multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT gemeili multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT zhangjing multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT wangmin multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT nieneng multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT jinpeng multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia AT zhengyizhou multifacetedcharacterizationofthesignaturesandefficacyofmesenchymalstemstromalcellsinacquiredaplasticanemia |