Immunomodulatory Properties of Mesenchymal Stem Cells Combined with Mycophenolate Mofetil Induce T Cell Regulation and Prolong Renal Allografts Survival in Cynomolgus Monkeys
Bibliographic record
Abstract
The induction of tolerance to allografts is one of the major goals in transplantation. Mesenchymal stem cells (MSCs) have been shown to be potent immunomodulatory and immunosuppressive properties in vitro and in vivo. However, to the clinical perspective of MSC-based cell therapy, it has not been clearly defined whether immunosuppressants currently utilized in the clinic may affect immunomodulatory capacities of MSCs. The aim of this study was to investigate the effect of combination therapies of MSCs and mycophenolate mofetil (MMF) on delaying acute rejection of renal allografts in Cynomolgus monkey model. MSCs were isolated from born marrow of Cynomolgus monkey. They were expanded and characterized by morphology, phenotypes and immunosuppressive functions. They were positive for CD90, CD73, CD29, CD105, and negative for CD45, CD34 and MHC-II. Monkeys received adoptive multiple infusions of autogeneic MSCs with a short-term and low-dose of MMF achieved long-term renal graft survival (>90 days post-transplantation) with normal serum creatinine (sCr) concentration and ultrasound imaging of transplanted kidney grafts. Confocal fluorescence microscopy analyses revealed that the transplanted PKH-26 labeled MSCs were found in renal allograft, spleen and lymph nodes of the recipients after the transplantation. The monkeys received MSCs showed high frequencies of CD4+CD25+Foxp3+ regulatory T cells (Tregs). An increased population of interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells and T helper (Th) 2-dominant cytokine shift were detected in survival recipients. Immunosuppressive effect of MSCs was not only showed in CD4+ and CD8+ cells, but also in their subsets of CD4+CD28+CD95- and CD8+CD28+CD95-naïve T cells. A depression in the percentages of CD4+CD28-CD95+ and CD8+CD28-CD95+ effecter memory T cells was observed in MSC treated recipients at the early stage of the treatment. In conclusion, this study shows synergistic effects of MSCs with short-term and low-dose MMF regimen in promoting renal allograft survival in Cynomolgus monkeys, also provides information to motivate the development of MSC therapy strategies in clinical transplantation.
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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) | 0.001 | 0.000 |
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".