Abstract 292: Hypoxia Induced Formation of Immunoproteasome Instigates Rejection of Allogeneic Mesenchymal Stem Cells in the Ischemic Heart
Bibliographic record
Abstract
Bone marrow derived allogeneic (donor derived) mesenchymal stem cells (MSCs) are considered to be prominent cell type for cardiac repair following a damage due to ischemic heart disease. Even though the outcome of initial allogeneic MSCs based clinical trials was encouraging, the overall enthusiasm lately has declined due to poor survival of transplanted cells in the ischemic heart. We reported in a rat model of myocardial infarction that allogeneic-MSCs became immunogenic after 5 weeks of transplantation and were rejected by host immune system that led to poor survival of implanted cells. The immunoprivilege of MSCs is preserved by absence of cell surface antigen, human leukocyte antigen (HLA) - DRα. We found that in normoxic MSCs, 26S proteasome degrades HLA-DRα and maintains immunoprivilege of MSCs. The exposure to hypoxia leads to inactivation of 26S proteasome and formation of immunoproteasome in MSCs, which is associated with upregulation and activation of HLA-DRα, and as a result MSCs become immunogenic. Furthermore, inhibition of immunoproteasome formation in hypoxic MSCs preserves the immunoprivilege. Therefore, hypoxia induced shift in the phenotype of proteasome from 26S toward immunoproteasome triggers loss of immunoprivilege of allogeneic MSCs and rejection. In our ongoing studies we are investigating if preventing the formation of immunoproteasome would prevent rejection of allogeneic MSCs in the ischemic heart and improve survival of transplanted cells. The outcome of these studies may provide molecular targets to plan interventions to preserve immunoprivilege of allogeneic MSCs in the ischemic heart and improve benefits of allogeneic MSCs for cardiac repair.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".