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Flexible wearable sensors:An emerging platform for monitoring of bacterial infection in skin wounds

Engineered Regeneration 2024年第2期5卷 186-198页

作者： Hao Meng Weicheng Zhong Kui Ma Jianlong Su Liqian Ma Yaying Hao Yufeng Jiang Xi Liu Xiaobing Fu Cuiping Zhang research Center for Tissue Repair and Regeneration Affiliated to the medical Innovation research Department PLA General Hospital and PLA Medical CollegeBeijing 100048PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine Beijing 100048PR China Beijing Key research Laboratory of Skin Injury Repair and RegenerationBeijing 100048PR China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China Department of Tissue Regeneration and Wound Repair PLA General HospitalBeijingPR China

Persistent inflammatory responses often occur when bacteria and other microorganisms frequently invade and colonize open wounds and eventually result in the formation of chronic ***,achieving real-time detection of invasive bacteria accurately and promptly is essential for efficient wound management and accelerat-ing the healing ***,flexible wearable sensors have garnered significant attention,especially those designed for monitoring real-time biophysical or biochemical signals in wound sites in a minimally invasive *** provide more precise and continuous monitoring data,making them as emerging tools for clinical *** this review,we first discuss the species and community distribution of different types of bacteria in chronic ***,we introduce currently developed techniques for detecting bacteria at wound ***-lowing that,we discuss the recent progress and unresolved issues of various flexible wearable sensors in detecting bacteria at wound *** believe that this review can provide meaningful guidance for the development of flexible wearable sensors for bacteria detection.

关键词： Flexible wearable sensors Chronic wounds Bacterial infections Real-time detection

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Autophagy and circadian rhythms:interactions and clinical implications

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BIOCELL 2024年第1期48卷 33-45页

作者： TIANKAI DI ZHIFEI ZHOU FEN LIU YUJIANG CHEN LULU WANG State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi Clinical Research Center for Oral DiseasesDepartment of Pediatric DentistrySchool of StomatologyThe Fourth Military Medical UniversityXi’an710032China Department of Stomatology The 969th HospitalJoint Logistics Support Force of the Chinese People’s Liberation ArmyHohhot010000China Department of Stomatology General Hospital of Tibetan Military CommandLhasa850000China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine research Clinical Research Center of Shaanxi Province for Dental and Maxillofacial DiseasesDepartment of Pediatric DentistryCollege of StomatologyXi’an Jiaotong UniversityXi’an710000China Department of Neurobiology and Institute of Neurosciences School of Basic MedicineFourth Military Medical UniversityXi’an710032China

Autophagy is a widespread biological process that controls cellular growth,survival,development,and *** rhythm is a recurring reaction of living organisms and behaviors to variations in surrounding brightness and *** of the fundamental physiological processes in mammals,such as the sleep-wake pattern and the rhythm of nutrition and energy metabolism,are governed by circadian *** has indicated that autophagy exhibits a specific circadian pattern in both normal and abnormal *** can modulate circadian rhythms by breaking down proteins that regulate the circadian *** potential regulatory connection between the two has been a popular subject of clinical and fundamental *** the interaction between circadian rhythm and autophagy could potentially lead to the development of novel approaches for disease treatment in the *** present analysis presented a summary of the molecular processes implicated in the interplay between autophagy and circadian rhythm,as well as the pathological importance of the disrupted regulatory association between these two phenomena.

关键词： Autophagy Circadian rhythms Mechanism Application

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Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles

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Bioactive Materials 2023年第9期27卷 257-270页

作者： Ziqiang Chu Qilin Huang Kui Ma Xi Liu Wenhua Zhang Shengnan Cui Qian Wei Huanhuan Gao Wenzhi Hu Zihao Wang Sheng Meng Lige Tian Haihong Li Xiaobing Fu Cuiping Zhang research Center for Tissue Repair and Regeneration Affiliated to the medical Innovation research Department PLA General Hospital28 Fuxing RoadBeijing100853PR China Chinese PLA medical School 28 Fuxing RoadBeijing100853PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU05151 Fucheng RoadBeijing100048PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key research Laboratory of Skin Injury Repair and RegenerationChinese PLA Hospital and PLA Medical College51 Fucheng RoadBeijing100048PR China Department of Dermatology China Academy of Chinese Medical ScienceXiyuan HospitalBeijing100091PR China Department of Wound Repair Institute of Wound Repair and Regeneration MedicineSouthern University of Science and Technology HospitalSouthern University of Science and Technology School of MedicineShenzhen518055PR China

Neutrophil extracellular traps(NETs)have been considered a significant unfavorable factor for wound healing in diabetes,but the mechanisms remain *** therapeutic application of small extracellular vesicles(sEVs)derived from mesenchymal stem cells(MSCs)has received considerable attention for their *** preconditioning is reported to enhance the therapeutic potential of MSC-derived sEVs in regenerative ***,the aim of this study is to illustrate the detailed mechanism of NETs in impairment of diabetic wound healing and develop a promising NET-targeting treatment based on hypoxic pretreated MSC-derived sEVs(Hypo-sEVs).Excessive NETs were found in diabetic wounds and in high glucose(HG)-induced *** research showed that high concentration of NETs impaired the function of fibroblasts through activating endoplasmic reticulum(ER)***-sEVs efficiently promoted diabetic wound healing and reduced the excessive NET formation by transferring *** analysis and RNA interference experiment revealed that miR-17-5p in Hypo-sEVs obstructed the NET formation by targeting TLR4/ROS/MAPK ***,miR-17-5p overexpression decreased NET formation and overcame NET-induced impairment in fibroblasts,similar to the effects of ***,we identify a previously unrecognized NET-related mechanism in diabetic wounds and provide a promising NET-targeting strategy for wound treatment.

关键词： Diabetic wound healing Neutrophil extracellular traps Small extracellular vesicles Hypoxia Endoplasmic reticulum stress

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Efficient and rapid conversion of human astrocytes and ALS mouse model spinal cord astrocytes into motor neuron-like cells by defined small molecules

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military medical research 2021年第1期8卷 62-78页

作者： An-Dong Zhao Hua Qin Meng-Li Sun Kui Ma Xiao-Bing Fu Tianjin medical University Tianjin 300070China research Center for Tissue Repair and Regeneration Affiliated to the medical Innovation research Division and 4th medical Center PLA General Hospital and PLA Medical College28 Fu Xing RoadHaidian DistrictBeijing 100853China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key research Laboratory of Skin Injury Repair and RegenerationBeijing 100048China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical SciencesBeijing 100048China

Background: Motor neuron degeneration or loss in the spinal cord is the characteristic phenotype of motor neuron diseases or spinal cord injuries. Being proliferative and located near neurons, astrocytes are considered ideal cell sources for regenerating ***: We selected and tested different combinations of the small molecules for inducing the conversion of human and mouse astrocytes into neurons. Microscopic imaging and immunocytochemistry analyses were used to characterize the morphology and phenotype of the induced neurons while RT-q PCR was utilized to analyze changes in gene expression. In addition, whole-cell patch-clamp recordings were measured to examine the electrophysiological properties of induced ***: The results showed that human astrocytes could be rapidly and efficiently converted into motor neuronlike cells by treatment with defined small molecules, with a yield of over 85% motor neuron-like cells attained. The induced motor neuron-like cells expressed the pan-neuronal markers TUJ1, MAP2, Neu N, and Synapsin 1 and motor neuron markers HB9, ISL1, CHAT, and VACh T. During the conversion process, the cells did not pass through a proliferative neural progenitor cell intermediate. The induced motor neurons were functional, showing the electrophysiological properties of neurons. The same chemical cocktail could induce spinal cord astrocytes from an amyotrophic lateral sclerosis mouse model carrying a SOD1 mutation to become motor neuron-like cells that exhibited a decrease in cell survival and an increase in oxidative stress compared to that observed in wild-type MNs derived from healthy mice. Moreover, the chemical induction reduced oxidative stress in the mutant ***: The results of the present study demonstrated the feasibility of chemically converting human and mouse astrocytes into motor neuron-like cells that are useful for neurodegenerative disease modeling and regenerative medicine.

关键词： Human astrocyte Motor neuron Reprogramming Transdifferentiation Conversion Regeneration Amyotrophic lateral sclerosis Neurodegenerative

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Reciprocal interaction between vascular niche and sweat gland promotes sweat gland regeneration

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Bioactive Materials 2023年第3期21卷 340-357页

作者： Xingyu Yuan Xianlan Duan Enhejirigala Zhao Li Bin Yao Wei Song Yuzhen Wang Yi Kong Shijun Zhu Fanliang Zhang Liting Liang Mengde Zhang Chao Zhang Deling Kong Meifeng Zhu Sha Huang Xiaobing Fu School of Medicine Nankai University94 Weijin RoadTianjin300071PR China research Center for Tissue Repair and Regeneration Affiliated to the medical Innovation research Department PLA General Hospital28 Fuxing RoadBeijing100853PR China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key research Laboratory of Skin Injury Repair and RegenerationChinese PLA General Hospital and PLA Medical College51 Fucheng RoadBeijing100048PR China College of Graduate Tianjin Medical UniversityTianjin300070PR China Institute of Basic medical research Inner Mongolia Medical UniversityHohhot010110Inner MongoliaPR China Academy of medical Engineering and Translational Medicine Tianjin University92 Weijin RoadTianjin300072PR China Department of Burn and Plastic Surgery Air Force Hospital of Chinese PLA Central Theater CommandDatong037000ShanxiPR China College of Life Science State Key Laboratory of Medicinal Chemical BiologyKey Laboratory of Bioactive Materials of Ministry of EducationNankai University94 Weijin RoadTianjin300071PR China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing100048PR China

The incorporation of vasculature is known to be effective in tissue or organ functional ***,a vague understanding of the interaction between epidermal appendages and their vascular niches is a foremost obstacle to obtaining sweat gland(SG)-specific vasculature ***,we map their precise anatomical con-nections and report that the interplay between SG cells(SGCs)and the surrounding vascular niche is key for glandular development and homeostasis *** replicate this interplay in vitro,we used three-dimensional(3D)bioprinting to generate reproducible SGC spheroids from differentiated adipose-derived mesenchymal stem cells(ADSCs).With dermal microvascular endothelial cells(DMECs),sacrificial templates made from poly(ε-caprolactone)(PCL)were fabricated to pattern the vascular *** interplay model promoted physiologically relevant vascularized glandular morphogenesis in vitro and in *** identified a reciprocal regulatory mechanism for promoting SGs regeneration via contact-independent cell communication and direct cell-cell interactions between SGs and the *** envision the successful use of our approach for vascularized organ regeneration in the near future.

关键词： Vascular niche 3D bioprinting Sweat gland-vasculature interaction model ECM scaffold Sweat gland regeneration

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A volar skin excisional wound model for in situ evaluation of multiple-appendage regeneration and innervation

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Burns & Trauma 2023年第1期11卷 560-572页

作者： Huanhuan Gao Yiqiong Liu Ziwei Shi Hongliang Zhang Mengyang Wang Huating Chen Yan Li Shaifei Ji Jiangbing Xiang Wei Pi Laixian Zhou Yiyue Hong Lu Wu Aizhen Cai Xiaobing Fu Xiaoyan Sun research Center for Tissue Repair and Regeneration Affiliated to medical Innovation research Department and 4^(th)medical Center PLA General Hospital and PLA Medical CollegePLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin InjuryRepair and RegenerationResearch Unit of Trauma CareTissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048P.R.China Institute of Chemistry Chinese Academy of Sciences2 Beiyi StreetZhong guan cunBeijing 100190P.R.China research Institute of General Surgery Department of General Surgerythe First Medical CenterPLA General Hospital28 Fu Xing RoadBeijing 100853P.R.China

Background:Promoting rapid wound healing with functional recovery of all skin appendages is the main goal of regenerative *** far current methodologies,including the commonly used back excisional wound model(BEWM)and paw skin scald wound model,are focused on assessing the regeneration of either hair follicles(HFs)or sweat glands(SwGs).How to achieve de novo appendage regeneration by synchronized evaluation of HFs,SwGs and sebaceous glands(SeGs)is still ***,we developed a volar skin excisional wound model(VEWM)that is suitable for examining cutaneous wound healing with multiple-appendage restoration,as well as innervation,providing a new research paradigm for the perfect regeneration of skin ***:Macroscopic observation,iodine-starch test,morphological staining and qRT-PCR anal-ysis were used to detect the existence of HFs,SwGs,SeGs and distribution of nerve fibres in the volar *** healing process monitoring,HE/Masson staining,fractal analysis and behavioral response assessment were performed to verify that VEWM could mimic the pathological process and outcomes of human scar formation and sensory function ***:HFs are limited to the *** are densely distributed in the footpads,scattered in the *** volar skin is richly *** wound area of the VEWM at 1,3,7 and 10 days after the operation is respectively 89.17%±2.52%,71.72%±3.79%,55.09%±4.94%and 35.74%±4.05%,and the final scar area accounts for 47.80%±6.22%of the initial *** the wound area of BEWM at 1,3,7 and 10 days after the operation are respectively 61.94%±5.34%,51.26%±4.89%,12.63%±2.86%and 6.14%±2.84%,and the final scar area accounts for 4.33%±2.67%of the initial *** analysis of the post-traumatic repair site for VEWM vs human was performed:lacunarity values,0.040±0.012 vs 0.038±0.014;fractal dimen-sion values,1.870±0.237 vs 1.903±*** nerve function of normal skin vs post-traumatic repair site was assessed

关键词： Wound healing Animal model Multiple appendages Innervation Regeneration evaluation Hair follicles Sweat gland Sebaceous gland

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P-MSC-derived extracellular vesicles facilitate diabetic wound healing via miR-145-5p/CDKN1A-mediated functional improvements of high glucose-induced senescent fibroblasts

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Burns & Trauma 2023年第1期11卷 325-348页

作者： Jianlong Su Qian Wei Kui Ma Yaxi Wang Wenzhi Hu Hao Meng Qiankun Li Yuehou Zhang Wenhua Zhang Haihong Li Xiaobing Fu Cuiping Zhang research Center for Tissue Repair and Regeneration Affiliated to the medical Innovation research Division and the 4th medical Center of Chinese PLA General Hospital 51 Fucheng RoadHaidian DistrictBeijing 100048China School of Medicine NanKai University94Weijin RoadNankai DistrictTianjin 300071China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU05151 Fucheng RoadHaidian DistrictBeijing 100048China Burn and Plastic Surgery Zhongda Hospital Affiliated Southeast UniversityDingjiaqiao 87Gulou DistrictNanjing 210009China Department of Wound Repair Institute of Wound Repair and Regeneration MedicineSouthern University of Science and Technology HospitalSouthern University of Science and Technology School of Medicine6019 Xililiuxian RoadNanshan DistrictShenzhen 518055China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key research Laboratory of Skin Injury Repair and Regeneration51 Fucheng RoadHaidian DistrictBeijing 100048China

Background:Persistent hyperglycaemia in diabetes causes functional abnormalities of human dermal fibroblasts(HDFs),partially leading to delayed skin wound *** vesicles(EVs)containing multiple pro-healing microRNAs(miRNAs)have been shown to exert therapeutic effects on diabetic wound *** present study aimed to observe the effects of EVs derived from placental mesenchymal stem cells(P-MSC-EVs)on diabetic wound healing and high glucose(HG)-induced senescent fibroblasts and to explore the underlying ***:P-MSC-EVs were isolated by differential ultracentrifugation and locally injected into the full-thickness skin wounds of diabetic mice,to observe the beneficial effects on wound healing in vivo by measuring wound closure rates and histological ***,a series of assays were conducted to evaluate the effects of low(2.28 x 1010 particles/ml)and high(4.56 x 1010 particles/ml)concentrations of P-MSC-EVs on the senescence,proliferation,migration,and apoptosis of HG-induced senescent HDFs in ***,miRNA microarrays and real-time quantitative PCR(RT-qPCR)were carried out to detect the differentially expressed miRNAs in HDFs after EVs *** RNA inhibitors,miRNA mimics,and small interfering RNA(siRNA)were used to evaluate the role of a candidate miRNA and its target genes in P-MSC-EV-induced improvements in the function of HG-induced senescent ***:Local injection of P-MSC-EVs into diabetic wounds accelerated wound closure and reduced scar widths,with better-organized collagen deposition and decreased p16INK4a *** vitro,P-MSC-EVs enhanced the antisenescence,proliferation,migration,and antiapoptotic abilities of HG-induced senescent fibroblasts in a dose-dependent ***-145-5p was found to be highly enriched in ***-145-5p inhibitors effectively attenuated the P-MSC-EV-induced functional improvements of senescent ***-145-5p mimics simulated the effects of P-MSC-EVs on funct

关键词： Diabetic wounds Mesenchymal stem cells Extracellular vesicles miR-145-5p CDKN1A Senescence Fibroblast Glucose

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MiR146a-loaded engineered exosomes released from silk fibroin patch promote diabetic wound healing by targeting IRAK1

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1224-1236页

作者： Qiankun Li Wenzhi Hu Qilin Huang Jie Yang Bingmin Li Kui Ma Qian Wei Yaxi Wang Jianlong Su Mengli Sun Shengnan Cui Rungong Yang Haihong Li Xiaobing Fu Cuiping Zhang Department of Tissue Repair and Regeneration The First Medical CenterChinese PLA General HospitalBeijing 100853China research Center for Tissue Repair and Regeneration Medical Innovation Research Department and the Fourth Medical CenterChinese PLA General HospitalBeijing 100048China Dermatology Department The Fourth Medical CenterChinese PLA General HospitalBeijing 100048China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key research Laboratory of Skin Injury Repair and RegenerationBeijing 100048China School of Medicine NanKai UniversityTianjing 300071China Department of Wound Repair and Dermatologic Surgery Taihe HospitalHubei University of MedicineShiyan 442000China

Unhealable diabetic wounds need to be addressed with the help of newer,more efficacious *** combined with biomaterials for sustained delivery of therapeutic agents are expected to bring new hope for chronic wound ***,the engineered exosomes modified for efficiently loading miR146a and attaching to silk fibroin patch(SFP)were demonstrated to promote diabetic wound *** fibroin binding peptide(SFBP)was screened through phage display,and SFBP-Gluc-MS2(SGM)and pac-miR146a-pac fusion protein were *** designed exosomes(SGM-Exos,miR146a-Exos,and SGM-miR146a-Exos)were isolated from the engineered placental mesenchymal stem cells(PMSCs)transduced with SGM or/and pac-miR146a-pac *** signals indicated SGM-Exo@SFP markedly increased the binding rate and the stability of ***,the loading efficiency of miR146a in SGM-miR146a-Exos was ten-fold higher than that in *** to untreated,SGM-miR146a-Exo-only treated,and SFP-only treated groups,SGM-miR146a-Exo@SFP drived wound healing associated with less inflammation,collagen deposition,and *** transcriptomics analysis suggested anti-inflammatory and regenerative effects with SGM-miR146a-Exo@SFP ***,we show efficient exosome@biomaterial-based miRNA delivery systems for regenerative medicine and tissue engineering.

关键词： miR146a wound healing

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Direct conversion of human fibroblasts into dopaminergic neuron-like cells using small molecules and protein factors

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military medical research 2021年第2期8卷 162-173页

作者： Hua Qin An-Dong Zhao Meng-Li Sun Kui Ma Xiao-Bing Fu research Center for Tissue Repair and Regeneration affiliated to the medical Innovation research Division and 4th medical Center PLA General Hospital and PLA Medical College28 Fu Xing RoadHaidian DistrictBeijing 100853China Tianjin medical University Tianjin 300070China PLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key research Laboratory of Skin Injury Repair and RegenerationBeijing 100048China research Unit of Trauma Care Tissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051Beijing 100048China

Background:Generation of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson’s *** studies have reported the generation of dopaminergic(DA)neurons from mouse and human fibroblasts by ectopic expression of transcription factors,in which genetic manipulation is associated with potential ***:The small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like ***,immunocytochemical,and RT-qPCR analyses were used to characterize the morphology,phenotype,and gene expression features of the induced *** wholecell patch-clamp recordings were exploited to measure the electrophysiological ***:Human IMR-90 fibroblasts were rapidly converted into DA neuron-like cells after the chemical induction using small molecules and protein factors,with a yield of approximately 95%positive TUJ1-positive *** induced DA neuron-like cells were immunopositive for pan-neuronal markers MAP2,NEUN,and Synapsin 1 and DA markers TH,DDC,DAT,and *** chemical induction process did not involve a neural progenitor/stem cell intermediate *** induced neurons could fire single action potentials,which reflected partially the electrophysiological properties of ***:We developed a chemical cocktail of small molecules and protein factors to convert human fibroblasts into DA neuron-like cells without passing through a neural progenitor/stem cell intermediate *** induced DA neuron-like cells from human fibroblasts might provide a cellular source for cell-based therapy of Parkinson’s disease in the future.

关键词： Human fibroblasts Dopaminergic neurons Parkinson's disease Small molecules Reprogramming Transdifferentiation

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Sebaceous gland reprogramming with a single gene, PPARG, and small molecules

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3913-3916页

作者： Yiqiong Liu Shuaifei Ji Huanhuan Gao Huating Chen Jiangbing Xiang Shaoyuan Cui Christos CZouboulis Aizhen Cai Xiaobing Fu Xiaoyan Sun research Center for Tissue Repair and Regeneration affiliated to the medical Innovation research Department and 4th medical Center PLA General Hospital and PLA Medical CollegePLA Key Laboratory of Tissue Repair and Regenerative Medicine and Beijing Key Research Laboratory of Skin InjuryRepairand RegenerationResearch Unit of Trauma CareTissue Repair and RegenerationChinese Academy of Medical Sciences2019RU051100048 BeijingP.R.China Department of Nephrology The First Medical CenterChinese PLA General HospitalState Key Laboratory of Kidney Diseases100048 BeijingChina Departments of Dermatology VenereologyAllergologyand ImmunologyStaedtisches Klinikum DessauBrandenburg Medical School Theodor Fontane and Faculty of Health Sciences BrandenburgDessauGermany Institute of General Surgery Department of General Surgerythe 1st Medical CenterPLA General Hospital28 Fu Xing Road100853 BeijingP.R.China

Dear Editor,Sebaceous glands(SG)contribute to 90%of the skin surface lipid production and play critical roles in regulating proper skin functions including epidermal barrier maintenance,dermal immune responses,and global body anti-microbial activities.1 Reduced sebaceous lipid has been implicated in diverse skin diseases,including scarring alopecia,inflammation,chronic itch,as well as premature aging of the skin.2 Especially,scar repair after deep burns or large-scale skin defect often leads to irreversible loss of *** to lacking SG,the regenerated tissues cannot fully recapitulate the structural and functional integrity of normal ***,generation of expandable SG cells with developmental and lipid-producing potentials represents a promising approach for treating diseased,damaged,or aged skin with better quality of ***,direct cellular reprogramming has been widely used for obtaining difficult-to-maintain human cells by cell type-specific transcription factors(TFs).

关键词： programming maintain irreversible

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