Administration of C5a Receptor Antagonist Improves the Efficacy of Human iPSCS-derived NS/PC Transplantation in the Acute Phase Of spinal Cord Injury
Bibliographic record
Abstract
Abstract Background: We previously reported the efficacy of human-induced pluripotent stem cells derived neural stem/progenitor cells (hiPSC-NS/PCs) transplantation for spinal cord injury (SCI) in the subacute phase. However, this procedure is not effective in the acute phase due to the inflammatory response occurring immediately after SCI, which negatively impacts transplanted cell survival. C5a, which is one of the complement components, is a powerful chemoattractant which recruits inflammatory cells through binding of the C5a receptor. We hypothesized that suppression of the inflammatory response immediately after SCI using a C5a receptor antagonist (C5aRA) as an immunosuppressant would improve the efficacy of hiPSC-NS/PCs transplantation for SCI in the acute phase.Methods: Immunodeficient SCID-Beige mice underwent contusion SCI at T10 and received C5aRA immediately after SCI. Inflammatory cytokines and inflammatory cells in the injured spinal cord tissue during the acute phase were quantified using quantitative PCR and flow-cytometry. Next, we randomly and blindly divided the SCI mice into 4 groups (PBS only, C5aRA only, PBS + transplantation (PBS+TP), C5aRA + transplantation (C5aRA+TP)). Immediately after SCI, C5aRA or PBS was injected intraperitoneally once a day for 4 consecutive days, and then, 5.0 × 105 hiPSC-NS/PCs were transplanted into the lesion epicenter on day 4 in the PBS+TP and C5aRA+TP groups. We evaluated cell survival rate, hindlimb motor function, and the differentiation profile of the graft hiPSC-NS/PCs.Results: C5aRA administration significantly reduced several inflammatory cytokines such as IL-1b, IL-6 and TNFα, as well as inflammatory cells after SCI. Within the transplantation groups, the C5aRA+TP group had better functional improvement as compared to the PBS only group. The C5aRA+TP group also had a significantly higher cell survival rate compared to the PBS+TP group. There were no significant differences in the differentiation profiles of grafted hiPSC-NS/PCs between the C5aRA+TP and PBS+TP groups.Conclusion: This study demonstrates that administration of C5aRA can suppress the inflammatory response during the acute phase of SCI, and also improve the survival rate of transplanted hiPSC-NS/PCs as well as enhance motor functional restoration. hiPSC-NS/PC transplantation with C5aRA is a promising treatment during the acute injury phase for SCI patients.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.002 | 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".