Evidence map›Paper›PMID 40579673›Full record

ArticleStem cell reviews and reports2025

Direct Lineage Reprogramming of Fibroblasts into Functional Keratinocyte-Like Cells via BMI1 and FGFR2b for Diabetic Wound Repair.

Hongrui Ma, Yashi Cao, Zizheng Gao, Zhifei Xu, Bo Yang, Peihua Luo, Yuhuai Hu, Qiaojun He

Abstract read
In one paragraph

Article in Stem cell reviews and reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Hongrui MaCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Hangzhou, 310058, Zhejiang, PR China.
Yashi CaoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Hangzhou, 310058, Zhejiang, PR China.
Zizheng GaoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Hangzhou, 310058, Zhejiang, PR China.
Zhifei XuCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Hangzhou, 310058, Zhejiang, PR China.
Bo YangInstitute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, Zhejiang, PR China.
Peihua LuoCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Hangzhou, 310058, Zhejiang, PR China. peihualuo@zju.edu.cn.
Yuhuai HuYuhong Pharmaceutical Technology Co. Ltd, Hangzhou, 310000, Zhejiang, China. huyuhuai1218@zju.edu.cn.
Qiaojun HeCenter for Drug Safety Evaluation and Research of Zhejiang University, College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Zijingang Campus, Hangzhou, 310058, Zhejiang, PR China. qiaojunhe@zju.edu.cn.

Funding

National Natural Science Foundation of China 82204516Pioneer" and "Leading Goose" R&D Program of Zhejiang province 2024C03144
6 · The paper itself

Abstract

backgroundThe limited regenerative capacity of epidermal cells following tissue injury impairs wound healing in diabetic foot ulcers (DFUs), contributing to elevated rates of amputation and mortality. Recent advances have demonstrated that somatic cells can be reprogrammed into diverse cell types through the application of defined reprogramming factors. This study aims to develop a safe, efficient, and clinically translatable strategy for skin regeneration via direct lineage reprogramming.

methodsWe established a novel reprogramming approach using a combination of two factors, BMI1 and FGFR2b (termed B2), to induce fibroblast-to-keratinocyte-like cells (iKCs) conversion in vitro and delivered via adeno-associated virus 9 (AAV9) in vivo. Molecular and functional characteristics of iKCs were evaluated by qRT-PCR, Western blot, immunofluorescence, transcriptomic analysis, and in vitro differentiation assays. A diabetic (db/db) mouse skin wound model was used to assess the regenerative potential and therapeutic effects. Statistical significance was determined using Student's t-test or one-way ANOVA.

resultsiKCs-B2 (Keratinocyte-like cells form from B2-infected L929) exhibited both morphological and functional characteristics comparable to primary keratinocytes. In vivo, AAV9-mediated delivery of B2 factors significantly promoted wound closure, reconstructed stratified epithelium, restored barrier function, and markedly reduced the mortality rate.

conclusionsThis study presents a safe and effective direct reprogramming strategy for skin regeneration, bypassing the pluripotent stage and avoiding cell transplantation. The B2 combination provides a novel molecular tool for wound repair and offers translational potential for treating non-healing wounds such as DFUs.

Indexed as

Cell LineageCellular ReprogrammingDiabetic FootFibroblastsKeratinocytesPolycomb Repressive Complex 1Proto-Oncogene ProteinsReceptor, Fibroblast Growth Factor, Type 2Wound HealingAnimalsCell DifferentiationDependovirusMiceMice, Inbred C57BLBmi1 protein, mouseFgfr2 protein, mousePolycomb Repressive Complex 1Proto-Oncogene ProteinsReceptor, Fibroblast Growth Factor, Type 2Direct lineage reprogrammingEpigeneticsInduced keratinocyte-like cellsIn situ reprogrammingLineage reprogramming

Identifiers

PMID40579673
PMCPMC12408679

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.