Bibliographic record
Abstract
The adult human central nervous system (CNS) is an exquisitely complex structure that has very limited capacity for repair and regeneration. However, recent developments in stem cell biology may change this. A number of preclinical studies have demonstrated that grafting neural precursor cells for CNS injury/disorder confers beneficial effects, can repair damaged neural tissue, and promote functional recovery.1-3 These promising results from stem cell transplantation work provide a strong rationale to pursue clinical trials using stem cells for pathological conditions in CNS.4,5 On the other hand, there is much debate regarding the safety of intraspinal injections for cell transplantation.6 Although previous studies have shown that intraspinal transplantation into the spinal cord does not cause substantial damage or permanent loss of locomotor function, the animals used in this research were rats, and the study did not specifically focus on the transplantation method itself.7 A recent study conducted transplantation of human neural precursor cells into the cervical spinal cord in pigs and examined injection volume and speed.8 The current article reported by Gutierrez et al9 extends the previous results, and precisely evaluates the effects of intraspinal injection by investigating differing numbers and volume of injections. They found that, although transient loss of motor function was observed soon after injection, complete functional recovery was achieved by 2 weeks even when injection volume and number were increased. However, histological analysis revealed tissue damage when up to 50 μL of cells were injected per site. In addition, increased numbers of cell injections showed a nonsignificant trend toward increased risk of tissue damage. These findings emphasize the importance of caution in deciding on the optimal injecting conditions for clinical trials, especially with regard to injection volume, number of sites, speed of delivery, and cell concentration. It is interesting that motor function fully recovered even though damage to the spinal cord tissue was obvious on histological analysis. Because detailed data regarding the measurement of sensory function were not reported in this study, it is possible that this damage may have contributed to the occurrence of allodynia. Allodynia is associated with increased calcitonin gene-related peptide-immunoreactive sensory axons in dorsal horn.10 Higher expression of glial fibrillary acidic protein in transplanted cells is a contributory cause of neuropathic pain.10 Future study with detailed histological analysis will contribute to the validation of a safety protocol for these procedures. In terms of clinical relevance, it will be important, in future research, to track the injected cells and recipient tissues in live animals, with the use of imaging systems such as magnetic resonance imaging. Disclosure The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.
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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 | 0.009 | 0.082 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.003 | 0.004 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.013 | 0.006 |
| Scholarly communication | 0.013 | 0.006 |
| Open science | 0.006 | 0.006 |
| Research integrity | 0.171 | 0.083 |
| Insufficient payload (model declined to judge) | 0.027 | 0.018 |
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".