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Photobiomodulation:a novel approach to promote trans-differentiation of adipose-derived stem cells into neuronal-like cells

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Neural Regeneration Research 2025年第2期20卷 598-608页

作者： Daniella Da Silva Madeleen Jansen van Rensburg Anine Crous Heidi Abrahamse Laser Research Centre Faculty of Health SciencesUniversity of JohannesburgDoornfonteinJohannesburgSouth Africa

Photobiomodulation,originally used red and near-infrared lasers,can alter cellular *** has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of *** this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain *** investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/*** adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory *** findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control ***,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal *** biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic ***,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.

关键词： differentiation inducers green photobiomodulation immortalized adipose-derived stem cell near-infrared photobiomodulation neurodegenerative disease neurogenesis photobiomodulation trans-differentiation

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Single-cell transcriptomics reveals neural stem cell trans-differentiation and cell subpopulations in whole heart decellularized extracellular matrix

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Biophysics Reports 2024年第4期10卷 241-253页

作者： Xiaoning Yang Yuwei Zhao Wei Liu Zhongbao Gao Chunlan Wang Changyong Wang Siwei Li Xiao Zhang Beijing Institute of Basic Medical Sciences

The whole heart decellularized extracellular matrix(ECM) has become a promising scaffold material for cardiac tissue engineering. Our previous research has shown that the whole heart acellular matrix possesses the memory function regulating neural stem cells(NSCs) trans-differentiating to cardiac lineage cells. However, the cell subpopulations and phenotypes in the trans-differentiation of NSCs have not been clearly identified. Here, we performed single-cell RNA sequencing and identified 2,765 cells in the recellularized heart with NSCs revealing the cellular diversity of cardiac and neural lineage, confirming NSCs were capable of trans-differentiating into the cardiac lineage while maintaining the original ability to differentiate into the neural lineage. Notably, the trans-differentiated heart-like cells have dual signatures of neuroectoderm and cardiac mesoderm. This study unveils an in-depth mechanism underlying the trans-differentiation of NSCs and provides a new opportunity and theoretical basis for cardiac regeneration.

关键词： Single-cell transcriptomics Neural stem cell trans-differentiation Decellularized extracellular matrix Cardiac lineage cells

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Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas

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Protein & Cell 2023年第2期14卷 105-122页

作者： Fangyu Wang Xuan Liu Shaowen Li Chen Zhao Yumei Sun Kuan Tian Junbao Wang Wei Li Lichao Xu Jing Jing Juan Wang Sylvia MEvans Zhiqiang Li Ying Liu Yan Zhou Department of Neurosurgery Zhongnan hospital of Wuhan UniversityFrontier Science Center for Immunology and MetabolismMedical Research InstituteThe RNA InstituteCollege of Life SciencesWuhan UniversityWuhan 430071China Department of Neurology The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China Skaggs School of Pharmacy Department of MedicineDepartment of PharmacologyUniversity of California at San DiegoLa JollaCA 92093USA

Glioblastoma multiforme(GBM),a highly malignant and heterogeneous brain tumor,contains various types of tumor and non-tumor *** GBM cells can trans-differentiate into non-neural cell types,including mural cells or endothelial cells(ECs),to support tumor growth and invasion remains *** we generated two genetic GBM models de novo in immunocompetent mouse brains,mimicking essential pathological and molecular features of human ***-tracing and transplantation studies demonstrated that,although blood vessels in GBM brains underwent drastic remodeling,evidence of trans-differentiation of GBM cells into vascular cells was barely ***,GBM cells could promiscuously express markers for mural cells during ***,single-cell RNA sequencing showed that patterns of copy number variations(CNVs)of mural cells and ECs were distinct from those of GBM cells,indicating discrete origins of GBM cells and vascular ***,single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate *** than expansion owing to trans-differentiation,vascular cell expanded by proliferation during ***,cross-lineage trans-differentiation of GBM cells is very unlikely to occur during *** findings advance understanding of cell lineage dynamics during gliomagenesis,and have implications for targeted treatment of GBMs.

关键词： glioblastoma mural cells endothelial cells trans-differentiation lineage tracing single-cell sequencing copy number variation

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Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells

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World Journal of Gastroenterology 2007年第24期13卷 3342-3349页

作者： Xiao-Hong Wu Cui-Ping Liu Kuan-Feng Xu Xiao-Dong Mao Jian Zhu Jing-Jing Jiang Dai Cui Mei Zhang Yu Xu Chao Liu Department of Endocrinology First Affiliated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China

AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat. METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. insulin release after glucose challenge was tested with ELiSA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry. RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d ***: Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro . Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.

关键词： Bone marrow mesenchymal stem cells trans-differentiation Islet Insulin transplantation

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The role of dendritic cells derived osteoclasts in bone destruction diseases

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Genes & Diseases 2021年第4期8卷 401-411页

作者： Bo Wang Yutong Dong Zhansong Tian Yueqi Chen Shiwu Dong Department of Biomedical Materials Science Third Military Medical University(Army Medical University)Chongqing400038PR China Battalion of Basic Medical Sciences Third Military Medical University(Army Medical University)Chongqing400038PR China Department of Orthopedics Southwest HospitalThird Military Medical University(Army Medical University)Chongqing400038PR China State Key Laboratory of Trauma Burns and Combined InjuryThird Military Medical University(Army Medical University)Chongqing400038PR China

The bone is previously considered as a dominant organ involved in the processes of ***,in the past two decades,a large number of studies have suggested that the skeletal system closely coordinated with the immune system so as to result in the emerging area of'osteoimmunology'.In the evolution of many kinds of bone destruction-related dis-eases,osteoclasts could differentiate from dendritic cells,which contributed to increased expression of osteoclast-related membrane receptors and relatively higher activity of bone destruction,inducing sewere bone destruction under inflammatory *** fac-tors could influence the interaction between osteoclasts and dendritic cells,contributing to the pathogenesis of several bone diseases in the context of inflammation,including both im-munocytes and a large number of *** addition,the products of osteoclasts released from bone destruction area serve as important signals for the differentiation and activation of immature dendritic ***,the border between the dendritic cell-rela ted immune response and osteoclast-related bone destruction has gradually *** cells and osteoclasts cooperate with each other to mediate bone destruction and bone remodelling under inflammatory *** this review,we will pay attention to the interactions be-tween dendritic cells and osteoclasts in physiological and pathological conditions to further understand the skeletal system and identifty potential new therapeutic targets for the future by summarizing their significant roles and molecular mechanisms in bone destruction.

关键词： Bone destruction diseases Dendritic cells Osteoclasts Osteoimmunology trans-differentiation

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The overexpression of Rps14 in Lgr5+progenitor cells promotes hair cell regeneration in the postnatal mouse cochlea

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Engineered Regeneration 2023年第3期4卷 328-336页

作者： Jingru Ai Pei Jiang Jingyuan Huang Hairong Xiao Yanqin Lin Mingchen Dai Yintao Wang Yuan Zhang Mengyao Tian Renjie Chai Shasha Zhang State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China Department of Otolaryngology Head and Neck Surgery Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsu Provincial Key Medical Discipline(Laboratory)NanjingChina Research Institute of Otolaryngology NanjingChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Department of Otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduChina Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijingChina Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

Sensory hair cells(HCs)in the cochlea cannot regenerate spontaneously in adult mammals after being damaged by external or genetic ***,several genes and signaling pathways are reported to induce cochlear HC regeneration at the early neonatal ***14 encodes a ribosomal protein that is involved in the regulation of cell differentiation and proliferation in ***,its roles in the cochlea have not been reported in ***,we specifically overexpressed Rps14 in Lgr5+progenitor cells in the newborn mouse cochlea and found that Rps14 conditional overexpression(cOE)mice had significantly increased the ectopic HCs,including inner and outer *** further explored the source of these ectopic HCs and found no EdU+supporting cells observed in the Rps14 cOE *** lineage tracing results,on the other hand,revealed that Rps14 cOE mice had significantly more tdTomato+HCs in their cochleae than control *** results indicated that regenerated HCs by cOE of Rps14 are most likely derived from inducing the direct trans-differentiation of Lgr5+progenitor cells into ***,real-time qPCR results suggested that the transcription factor genes Atoh1 and Gfi1,which are important in regulating HC differentiation,were upregulated in the cochlear basilar membrane of Rps14 cOE *** summary,this study provides in vivo evidence that,in the postnatal mouse cochlea,Rps14 is a potential gene that can promote the spontaneous trans-differentiation of Lgr5+progenitor cells into *** gene may one day be exploited as a therapeutic target for treating hearing loss.

关键词： Rps14 Lgr5+progenitor cells Ectopic hair cells Regeneration Proliferation trans-differentiation

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Putative epidermal stem cell convert into corneal epithelium-like cell under corneal tissue in vitro

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Science China(Life Sciences) 2007年第1期50卷 101-110页

作者： GAO Nan1, WANG ZhiChong1, HUANG Bing1, GE Jian1, LU Rong1, ZHANG KeFei1,2, FAN ZhiGang1, LU Li1, PENG Zhan1 & CUI GuangHui1 1 Key Laboratory of Ophthalmology (Sun Yat-sen University), Ministry of Education Zhongshan Ophthalmic Center, Guangzhou 510060, China 2 Liwan Hospital of Guangzhou Medical College, Guangzhou 510165, China Key Laboratory of Ophthalmology (Sun Yat-sen University) Ministry of Education China Zhongshan Ophthalmic Center Guangzhou China Liwan Hospital of Guangzhou Medical College Guangzhou China

Rhesus putative epidermal stem cells are being investigated for their potential use in regenerative corneal epithelium-like cells, which may provide a practical source of autologous seed cells for the construction of bioengineered corneas. The goal of this study was to investigate the potential of epi-dermal stem cells for trans-differentiation into corneal epithelium-like cells. Rhesus putative epidermal stem cells were isolated by type IV collagen attachment method. Flow cytometry analysis, immuno-histology and RT-PCR were conducted to identify the expression of specific markers (β1, α6 integrin, K15, K1/K10, K3/K12 and CD71) on the isolated rapid attaching cells. The isolated cells were cocultured with human corneal limbal stroma and corneal epithelial cells. After coculture, the expression of the same specific markers was evaluated in order to identify expression difference caused by the coculture conditions. K3/K12 expression was analyzed in coculture cells on day 2, 4, 6, 8 and 10. Putative epi-dermal stem cells in conditioned culture media were used as control. Putative epidermal stem cells were predominant in rapid attaching cells by type IV collagen attachment isolation. Before being co-cultured, the rhesus putative epidermal stem cells expressed K15, α6 and β1 integrin, but no CD71, K1/K10 and K3/K12. After coculture, these cells expressed K3/K12 (a marker of corneal epithelial cells), K15 and β 1 integrin, but no K1/K10. Cells being not coculture converted into terminally differentiated cells expressing K1/K10. These results indicate that rhesus putative epidermal stem cells can trans-differentiate into corneal epithelium-like cells and, therefore, may have potential therapeutic application as autologous seed cells for the construction of bioengineered corneas.

关键词： epidermal stem cells corneal epithelium cells trans-differentiation

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Skeletal Muscle-derived Stem Cells Exhibit Cardiocyte Competences

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第6期29卷 741-744页

作者：李进付德生洪光祥陈江海康皓陈振兵 Department of Hand Surgery Union Hospital Tongji Medical College Huazhong University of Science and Technology Department of Orthopedics Yingshan County People’s Hospital

Adult stem cells from skeletal muscle cells were induced to differentiate into cardiocytes to see if stem cells from another different but histologically-comparable tissues can differentiate to the target cells. Skeletal muscles-derived stem cells （MDSCs） were isolated from adult skeleton muscle tissues by differential adhesion, and immunocytochemically identified by using Sca-1. In order to induce the proliferation but not differentiation of MDSCs, the cells were cultured in Dulbecco’s modified Eagle’s medium/F12 （DMEM/F12） supplemented with 1：50 B27, 20 ng/mL basic fibroblast growth factor （bFGF）, 20 ng/mL epidermal growth factor （EGF） in a suspension for 6 days. Then these stem cells were treated with 5 μmol/L 5-azacytidine for 24 h in an adherence culture. The characteristics of induced cells were examined by immunocytochemistry, quantitative real time RT-PCR and morphological observation of cell phenotype. Our results showed that the appearance of some cells gradually changed from spindle-shape into polygonal or short-column-shape. Some of these post-treated cells could contract spontaneously and rhythmically. The expression of GATA-4 and cTnT was increased 1 and 2 week（s） after the treatment. And about 16.6% of post-treated cells were cTnT-positive. Therefore, we are led to conclude that skeletal muscle-derived stem cells could differentiate into cardiocyte-like cells, which exhibited some characteristics of cardiocytes.

关键词： skeletal muscle-derived stem cells trans-differentiation cardiocytes

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Reprogramming somatic cells to cells with neuronal characteristics by defined medium both in vitro and in vivo

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Cell Regeneration 2015年第1期4卷 123-131页

作者： Songwei He Yiping Guo Yixin Zhang Yuan Li Chengqian Feng Xiang Li Lilong Lin Lin Guo Haitao Wang Chunhua Liu Yi Zheng Chuanming Luo Qiang Liu Fuhui Wang Hao Sun Lining Liang Lingyu Li Huanxing Su Jiekai Chen Duanqing Pei Hui Zheng CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences#190 Kaiyuan AvenueScience CityGuangzhou 510530China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Anhui University Hefei 230601China

Background:Currently,direct conversion from somatic cells to neurons requires virus-mediated delivery of at least one transcriptional factor or a combination of several small-molecule *** of transcriptional factors may affect genome stability,while small-molecule compounds may require more evaluations when applied in ***,a defined medium with only conventional growth factors or additives for cell culture is desirable for inducing neuronal ***:Here,we report that a defined medium(5C)consisting of basic fibroblast growth factor(bFGF),N2 supplement,leukemia inhibitory factor,vitamin C(Vc),andβ-mercaptoethanol(βMe)induces the direct conversion of somatic cells to cells with neuronal *** of 5C medium converted mouse embryonic fibroblasts(MEFs)into TuJ+neuronal-like cells,which were capable of survival after being transplanted into the mouse *** same 5C medium could convert primary rat astrocytes into neuronal-like cells with mature electrophysiology characteristics in vitro and facilitated the recovery of brain injury,possibly by inducing similar conversions,when infused into the mouse brain in ***,5C medium could also induce neuronal characteristics in several human cell ***:In summary,this 5C medium not only provides a means to derive cells with neuronal characteristics without viral transfection in vitro but might also be useful to produce neurons in vivo for neurodegenerative disease treatment.

关键词： Neurons Somatic cells Astrocytes trans-differentiation Defined medium

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transitions between mesenchymal and epithelial states and the concomitant gene expression changes

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Science Foundation in China 2016年第1期24卷 50-62页

作者： LIANG LiNing SUN Hao LI LingYu ZHENG Hui CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences Anhui University

Epithelial-mesenchymal transition(EMT),mesenchymal-epithelial transition(MET),and even the sequential EMT-MET can be observed during multiple cell fate conversions including cancer progression and embryonic *** the current review,we first focused on the existence and beneficial roles of the sequential EMT-MET during three typical cell fate conversions,differentiation from pluripotent stem cells(PSCs)to neurons,de-differentiation from mouse embryonic fibroblasts(MEFs)to PSCs,and trans-differentiation from MEFs to *** tried to provide some preliminary hypotheses to connect EMT-MET and cell fate conversions,like the possible contributions of the intermediate mesenchymal state to iPSCs generation and *** intermediate mesenchymal state during sequential EMT-MET was further discussed by exploring the conserved signatures on gene expression during a variety of *** on the interaction among vitamin C,DNA methylation,and EMT/MET was also provided.

关键词： Epithelial-mesenchymal transition Cell fate conversions Reprogramming trans-differentiation

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