ArticleCell death & disease2019
Hypoxia-induced 26S proteasome dysfunction increases immunogenicity of mesenchymal stem cells.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Role of the Proteasome System in Shaping Cellular Immunological Characteristics and Its Impact in Modulating the Pathogenesis of Immune-Related Diseases.Cells, tissues, organs · 2026Review
- Hypoxia Increases Connexin46 and Connexin43 Levels in KNS-42 Glioblastoma Cells.International journal of molecular sciences · 2026Article
- Adipose Tissue and Bone Marrow-Derived Mesenchymal Stem Cells are not Really the Same: Investigating the Differences in Their Immunomodulatory, Migratory, and Adhesive Profile.Biochemical genetics · 2025Article
- Enhancing the functionality of mesenchymal stem cells: An attractive treatment strategy for metabolic dysfunction-associated steatotic liver disease?World journal of stem cells · 2024Article
- The application potential of iMSCs and iMSC-EVs in diseases.Frontiers in bioengineering and biotechnology · 2024Review
- Enhancing mesenchymal stem cell survival and homing capability to improve cell engraftment efficacy for liver diseases.Stem cell research & therapy · 2023Review
- Recent advances in pre-conditioned mesenchymal stem/stromal cell (MSCs) therapy in organ failure; a comprehensive review of preclinical studies.Stem cell research & therapy · 2023Review
- Proteasome Dysfunction Leads to Suppression of the Hypoxic Response Pathway in Arabidopsis.International journal of molecular sciences · 2022Article
- Cardiac ischemia on-a-chip to investigate cellular and molecular response of myocardial tissue under hypoxia.Biomaterials · 2022Article
- Editorial: The Analysis of Nanovesicles, Biomaterials and Chemical Compounds: Assisting the Promotion of Angiogenesis and Enhancing Tissue Engineering Strategies.Frontiers in cardiovascular medicine · 2022Article
- Engineering of human mesenchymal stem cells resistant to multiple natural killer subtypes.International journal of biological sciences · 2022Article
- Review
- Reduced Granule Cell Proliferation and Molecular Dysregulation in the Cerebellum of Lysosomal Acid Phosphatase 2 (ACP2) Mutant Mice.International journal of molecular sciences · 2021Article
- Hypoxia-induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of mesenchymal stem cells.Cell death & disease · 2020Article
- Proteomic Analysis of Two Weight Classes of Mule Duck "Frontiers in physiology · 2020Article
- Cross talk between 26S proteasome and mitochondria in human mesenchymal stem cells' ability to survive under hypoxia stress.The journal of physiological sciences : JPS · 2019Article
- Substantial Overview on Mesenchymal Stem Cell Biological and Physical Properties as an Opportunity in Translational Medicine.International journal of molecular sciences · 2019Review
- Addressing the impact of different fetal bovine serum percentages on mesenchymal stem cells biological performance.Molecular biology reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Bone marrow-derived allogeneic (donor derived) mesenchymal stem cells (MSCs) are immunoprivileged and are considered to be prominent candidates for regenerative therapy for numerous degenerative diseases. Even though the outcome of initial allogeneic MSCs based clinical trials was encouraging, the overall enthusiasm, of late, has dimmed down. This is due to failure of long-term survival of transplanted cells in the recipient. In fact, recent analyses of allogeneic MSC-based studies demonstrated that cells after transplantation turned immunogenic and were subsequently rejected by host immune system. The current study reveals a novel mechanism of immune switch in MSCs. We demonstrate that hypoxia, a common denominator of ischemic tissues, induces an immune shift in MSCs from immunoprivileged to immunogenic state. The immunoprivilege of MSCs is preserved by downregulation or the absence of major histocompatibility complex class II (MHC-II) molecules. We found that 26S proteasome-mediated intracellular degradation of MHC-II helps maintain the absence of MHC-II expression on cell surface in normoxic MSCs and preserves their immunoprivilege. The exposure to hypoxia leads to dissociation of 19S and 20S subunits, and inactivation of 26S proteasome. This prevented the degradation of MHC-II and, as a result, the MSCs became immunogenic. Furthermore, we found that hypoxia-induced decrease in the levels of a chaperon protein HSP90α is responsible for inactivation of 26S proteasome. Maintaining HSP90α levels in hypoxic MSCs preserved the immunoprivilege of MSCs. Therefore, hypoxia-induced inactivation of 26S proteasome assembly instigates loss of immunoprivilege of allogeneic mesenchymal stem cells. Maintaining 26S proteasome activity in mesenchymal stem cells preserves their immunoprivilege.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.