From Fat to Skin
Bibliographic record
Abstract
INTRODUCTION: The ideal aim of skin regeneration is to find a means to replace or regenerate this complex organ with normal appearance and with complete functionality. This process can be done in-vivo or in vitro and may require cells, natural or synthetic cell-supporting scaffold materials and bioactive molecules among other components. Unfortunately, current treatments are not capable of inducing permanent satisfying replacements.1–2 Human adipose-derived stem cells (ASC) have been shown to differentiate in-vitro into both mesenchymal lineages (adipogenesis, chondrogenesis, osteogenesis, fibroblasts) and non-mesenchymal lineages (endothelium, smooth muscle, cardiomyocytes, hepatocytes and neuron-like cells), confirming their transdifferentiation ability.3–5 This versatile differentiation potential and their easy availability, places adipose-derived stem cells at the advancing front of stem cell-based therapies. We hypothesized that ASC have the capacity to transdifferentiate into keratinocyte-like cells and furthermore be able to engineer a stratified epidermis. Methods and Results: ASC were successfully isolated from patients undergoing liposuction using Fluorescent-activated cell sorting technique (FACS). Pure populations of ASC were either co-cultured with human keratinocytes or with keratinocyte conditioned media. After a 14-day incubation period, ASC developed a polygonal cobblestone shape characteristic of human keratinocytes. Western blot and q-PCR analysis showed the presence of specific keratinocyte markers including Cytokeratin-5, Involucrin, Filaggrin and Stratifin in these keratinocyte-like cells (KLC); these markers were absent in undifferentiated ASC. To further evaluate if KLC were capable of stratification akin to human keratinocytes, ASC were seeded on top of human decellularized dermis and cultured in the presence of Epidermal Growth Factor (EGF) and 1.8mM Ca2+ concentrations. Histological analysis demonstrated a stratified structure similar to that observed in normal skin. Furthermore, immunohistochemical analysis revealed the presence of keratinocyte markers such as Involucrin, Cytokeratin-5 and Cytokeratin-10. CONCLUSION: In conclusion this study demonstrates for the first time that ASC have the capacity to transdifferentiate into KLC and also to produce a stratified epidermis. This study suggests that adipose tissue is potentially a readily available and accessible source of keratinocyte-like cells, particularly for severe wounds encompassing large surface areas of the body and requiring prompt epithelialization.
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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) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.044 | 0.024 |
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".