Skin-Derived Stem Cells: A Source of Schwann Cells that Survive and Ensheath Axons on Transplantation into Peripheral Nerve
Bibliographic record
Abstract
Clones of neural-crest-derived progenitor cells from skin dermis (termed SKPs for skin-derived precursors) can proliferate and differentiate under appropriate culture conditions to produce neurons, glia, and mesodermal cells. The authors hypothesized that SKPs introduced into a nerve will 1) survive and spread within the nerve; 2) differentiate into Schwann cells (SCs); and 3) ensheath regenerating axons from the proximal nerve stump. Donor SKPs were generated from embryonic transgenic mice (E17–18) expressing the enhanced green fluorescent protein (GFP). To encourage SC differentiation, SKPs were cultured for 1 week in DMEM:F12 media at a 3:1 ratio, supplemented with 1% N2, 10ng/ml heregulin and 4 umol forksolin. Immunosuppressed recipient adult male Sv129 mice underwent nerve surgery and inoculation with SKPs. The sciatic nerve was exposed in the proximal thigh and crushed for 1 min using #4 jewelers' forceps. An injection, 5 mm distal to the crush injury site, of 3 ul of SKP cells (∼150,000/ul) was made in the subepineurium using a 33-gauge Hamilton syringe. Controls consisted of normal mice and mice with crush injuries receiving a 3-ul injection of diluent. At 1–4 weeks following nerve injury (n = 5/time point), nerve samples were collected for immunohistochemistry. Confocal imaging and analysis of double-stained sections were done to assess the relationship between SKPs and axons. SKPs (GFP + cells) survived for up to 4 weeks and spread within the endoneurium for several millimeters in normal sciatic nerve. Both naïve and pre-differentiated SKPs co-expressed SC markers (MBP and PMP-22) in vivo and appeared to associate with axons within the sciatic nerve. Moreover, these SKPs, when injected into the nerve distal to the crush, expressed myelin proteins and became closely associated with regenerating (NF +) axons. In separate experiments, semithin section and immunogold EM analysis from Shiverer mice nerve receiving SKPs conclusively demonstrated that transplanted (MBP + and GFP +) cells myelinated Shiverer axons. SKPs survive, express SC markers, associate with axons, and indeed myelinate axons in regenerating peripheral nerves. Moreover, naïve SKPs can differentiate into SCs within the nerve, suggesting that axon-derived factors can drive this differentiation. These results suggest that skin may provide an accessible autologous source of Schwann cells for nerve transplantation and nerve 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".