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Transplantation of tissue-engineered human corneal epithelium in limbal stem cell deficiency rabbit models 被引量:4
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作者 Bin Xu Ting-Jun Fan +6 位作者 Jun Zhao Ai Sun Rui-Xin Wang Xiu-Zhong Hu Hao-Ze Yu Xian-Yuan Fan and Xiao-Hui Xu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2012年第4期424-429,共6页
AIM: To evaluate the biological functions of tissue-engineered human corneal epithelium (TE-HCEP) by corneal transplantation in limbal stem cell deficiency (LSCD) rabbit models. METHODS: TE-HCEPs were reconstructed wi... AIM: To evaluate the biological functions of tissue-engineered human corneal epithelium (TE-HCEP) by corneal transplantation in limbal stem cell deficiency (LSCD) rabbit models. METHODS: TE-HCEPs were reconstructed with DiI-labeled untransfected HCEP cells and denuded amniotic membrane (dAM) in air-liquid interface culture, and their morphology and structure were characterized by hematoxylin-eosin (HE) staining of paraffin-sections, immunohistochemistry and electron microscopy. LSCD models were established by mechanical and alcohol treatment of the left eyes of New Zealand white rabbits, and their eyes were transplanted with TE-HCEPs with dAM surface outside by lamellar keratoplasty (LKP). Corneal transparency, neovascularization, thickness, and epithelial integrality of both traumatic and post transplantation eyes were checked once a week by slit-lamp corneal microscopy, a corneal pachymeter, and periodic acid-Schiff (PAS) staining. At day 120 post surgery, the rabbits in each group were sacrificed and their corneas were examined by DiI label observation, HE staining, immunohistochemistry and electron microscopy. RESULTS: After cultured for 5 days on dAM, HCEP cells, maintaining keratin 3 expression, reconstructed a 6-7 layer TE-HCEP with normal morphology and structure. The traumatic rabbit corneas, entirely opaque, conjunctivalized and with invaded blood vessels, were used as LSCD models for TE-HCEP transplantation. After transplantation, obvious edema was not found in TE-HCEP-transplanted corneas which became more and more transparent, the invaded blood vessels reduced gradually throughout the monitoring period. The corneas decreased to normal thickness on day 25, while those of dAM eyes were over 575 mu m in thickness during the monitoring period. A 45 layer of epithelium consisting of TE-HCEP originated cells attached tightly to the anterior surface of stroma was reconstructed 120 days after TE-HCEP transplantation, which was similar to the normal control eye in morphology and structure. In contrast, intense corneal edema, turbid, invaded blood vessels were found in dAM eyes, and no multilayer epithelium was found but only a few scattered conjunctiva-like cells appeared. CONCLUSION: The TE-HCEP, with similar morphology and structure to those of innate HCEP, could reconstruct a multilayer corneal epithelium with normal functions in restoring corneal transparency and thickness of LSCD rabbits after transplantation. It may be a promising HCEP equivalent for clinical therapy of corneal epithelial disorders. 展开更多
关键词 tissue-engineered human corneal epithelium limbal stem cell deficiency rabbit lamellar keratoplasty human corneal epithelial cells denuded amniotic membrane RECONSTRUCTION
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Therapeutic effect of secretome from TNF-αstimulated mesenchymal stem cells in an experimental model of corneal limbal stem cell deficiency 被引量:2
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作者 Guo-Hu Di Xia Qi +4 位作者 Jing Xu Chao-Qun Yu Qi-Long Cao Zhi-Jun Xing Zhi-Chao Li 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2021年第2期179-185,共7页
AIM:To explore the secretome efficacy in tumor necrosis factor(TNF)-αstimulated mouse mesenchymal stem cells(MSCs)in a murine model of corneal limbal alkali injury.METHODS:Corneal limbal stem cell deficiency(LSCD)was... AIM:To explore the secretome efficacy in tumor necrosis factor(TNF)-αstimulated mouse mesenchymal stem cells(MSCs)in a murine model of corneal limbal alkali injury.METHODS:Corneal limbal stem cell deficiency(LSCD)was created in the eyes of male C57 mice.Concentrated conditioned medium from TNF-αstimulated MSCs(MSC-CMT)was applied topically for 4 wk,with basal medium and conditioned medium from MSCs as controls.Corneal opacification,corneal inflammatory response,and corneal neovascularization(NV)were evaluated.Corneal epithelial cell apoptosis,corneal conjunctivation,and inflammatory cell infiltration were assessed with TUNEL staining,CK3 and Muc-5 AC immunostaining,and CD11 b immunofluorescence staining,respectively.The effect of TSG-6 was further evaluated by knockdown with short hairpin RNA(sh RNA).RESULTS:Compared to the controls,topical administration of MSC-CMT significantly ameliorated the clinical symptoms of alkali-induced LSCD,with restrained corneal NV,reduced corneal epithelial cell apoptosis,and inhibition of corneal conjunctivation.In addition,MSC-CMT treatment significantly reduced CD11 b+inflammatory cell infiltration,and inhibited the expression of pro-inflammatory cytokines(IL-1β,TNF-αand IL-6).Furthermore,the promotion of corneal epithelial reconstruction by MSC-CMT was largely abolished by TSG-6 knockdown.CONCLUSION:Our study provides evidence that MSCCMT enhances the alleviation of corneal alkali injuries,partially through TSG-6-mediated anti-inflammatory protective mechanisms.MSC-CMT may serve as a potential strategy for treating corneal disorders. 展开更多
关键词 MSC-CMT limbal stem cell deficiency TSG-6
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Single-cell RNA sequencing in cornea research:Insights into limbal stem cells and their niche regulation 被引量:1
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作者 Di Sun Wei-Yun Shi Sheng-Qian Dou 《World Journal of Stem Cells》 SCIE 2023年第5期466-475,共10页
The corneal epithelium is composed of stratified squamous epithelial cells on the outer surface of the eye,which acts as a protective barrier and is critical for clear and stable vision.Its continuous renewal or wound... The corneal epithelium is composed of stratified squamous epithelial cells on the outer surface of the eye,which acts as a protective barrier and is critical for clear and stable vision.Its continuous renewal or wound healing depends on the proliferation and differentiation of limbal stem cells(LSCs),a cell population that resides at the limbus in a highly regulated niche.Dysfunction of LSCs or their niche can cause limbal stem cell deficiency,a disease that is manifested by failed epithelial wound healing or even blindness.Nevertheless,compared to stem cells in other tissues,little is known about the LSCs and their niche.With the advent of single-cell RNA sequencing,our understanding of LSC characteristics and their microenvironment has grown considerably.In this review,we summarized the current findings from single-cell studies in the field of cornea research and focused on important advancements driven by this technology,including the heterogeneity of the LSC population,novel LSC markers and regulation of the LSC niche,which will provide a reference for clinical issues such as corneal epithelial wound healing,ocular surface reconstruction and interventions for related diseases. 展开更多
关键词 CORNEA limbal stem cells Single cell RNA sequencing HETEROGENEITY Novel markers Niche regulation
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Comparative analysis of different feeder layers with 3T3 fibroblasts for culturing rabbits limbal stem cells 被引量:3
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作者 Hui-Xian Wang Xiao-Wei Gao +4 位作者 Bing Ren Yan Cai Wen-Jing Li Yu-Li Yang Yi-Jian Li 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2017年第7期1021-1027,共7页
AIM: To explore the possibility of human umbilical cord mesenchymal stem cells(h UCMSCs), human umbilical vein endothelial cells(h UVECs), human dental pulp stem cells(h DPSCs) and human periodontal ligament st... AIM: To explore the possibility of human umbilical cord mesenchymal stem cells(h UCMSCs), human umbilical vein endothelial cells(h UVECs), human dental pulp stem cells(h DPSCs) and human periodontal ligament stem cells(h PDLSCs) serving as feeder cells in co-culture systems for the cultivation of limbal stem cells.METHODS: Different feeder layers were cultured in Dulbecco's modified Eagle's medium(DMEM)/F12 and were treated with mitomycin C. Rabbits limbal stem cells(LSCs) were co-cultured on h UCMSCs, h UVECs, h DPSCs, h PDLSCs and NIH-3T3, and then comparative analysis were made between each group to see their respective colony-forming efficiency(CFE) assay and immunofluorescence(IPO13,CK3/12).RESULTS: The efficiency of the four type cells in supporting the LSCs morphology and its cellular differentiation was similar to that of NIH-3T3 fibroblasts as demonstrated by the immunostaining properties analysis, with each group exhibiting a similar strong expression pattern of IPO13, but lacking CK3 and CK12 expression in terms of immunostaining. But h UCMSCs, h DPSCs and h PDLSCs feeder layers were superior in promoting colony formation potential of cells when compared to h UVECs and feedercell-free culture.CONCLUSION: hUCMSCs, hDPSCs and hPDLSCs can be a suitable alternative to conventional mouse NIH-3T3 feeder cells, so that risk of zoonotic infection can be diminished. 展开更多
关键词 limbal stem cells feeder layers umbilical cord mesenchymal stem cells umbilical vein endothelial cells dental pulp stem cells periodontal ligament stem cells
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Focus on limbal stem cell deficiency and limbal cell transplantation 被引量:1
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作者 Emanuele Tonti Gregorio Antonio Manco +1 位作者 Leopoldo Spadea Marco Zeppieri 《World Journal of Transplantation》 2023年第6期321-330,共10页
Limbal stem cell deficiency(LSCD)causes severe vision impairment and can lead to blindness,representing one of the most challenging ocular surface disorders.Stem cell deficiency can be congenital or,more often,acquire... Limbal stem cell deficiency(LSCD)causes severe vision impairment and can lead to blindness,representing one of the most challenging ocular surface disorders.Stem cell deficiency can be congenital or,more often,acquired.The categorization of ocular surface transplantation techniques is crucial to achieving treatment homogeneity and quality of care,according to the anatomic source of the tissue being transplanted,genetic source,autologous or allogenic transplantation(to reflect histocompatibility in the latter group),and cell culture and tissue engineering techniques.The aim of this minireview is to provide a summary of the management of LSCD,from clinical characteristics and therapeutic outcomes to the development of novel therapeutic approaches.The manuscript also briefly summarizes recent findings in the current literature and outlines the future challenges to overcome in the management of the major types of ocular surface failure. 展开更多
关键词 limbal stem cell deficiency Conjunctival limbal autograft Conjunctival limbal allograft Keratolimbal allograft Cultivated limbal epithelial transplantation Simple limbal epithelial transplantation
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Investigation of immunogenicity of cryopreserved limbal stem cells
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作者 Yan Zhang, Li Sun 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2011年第6期590-593,共4页
AIM: To investigate changes in immunogenicity of cryopreserved limbal stem cells. METHODS: Cryopreserved limbal stem cells, fresh primary limbal stem cells and blank controls were inoculated subcutaneously in C57BL-6 ... AIM: To investigate changes in immunogenicity of cryopreserved limbal stem cells. METHODS: Cryopreserved limbal stem cells, fresh primary limbal stem cells and blank controls were inoculated subcutaneously in C57BL-6 mice and the percentage of CD25 cells in limbal explants was determined by flow cytometry at day 21 post inoculation. Morphological studies were performed by light and electron microscopy of limbal explant sections. RESULTS: The number of regional and systemic lymphocytes derived from cryopreserved limbal stem cells was lower than that from fresh primary limbal stem cells. CONCLUSION: Lymphocytes derived from cryopreserved limbal stem cells showed changes in immunogenicity, but the significance is unknown. The cryopreservation and thawing methods await further study. 展开更多
关键词 rabbit limbal stem cells CRYOPRESERVATION IMMUNOGENICITY EXPLANT
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Midterm outcomes of penetrating keratoplasty following allogeneic cultivated limbal epithelial transplantation in patients with bilateral limbal stem cell deficiency
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作者 Jun-Fa Xue Dong-Fang Li +6 位作者 Ya-Ni Wang Chen Chen Ru-Fei Yang Qing-Jun Zhou Ting Liu Li-Xin Xie Yan-Ling Dong 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2021年第11期1690-1699,共10页
AIM:To evaluate the midterm outcomes of penetrating keratoplasty(PK)following allogeneic cultivated limbal epithelial transplantation(CLET)for bilateral total limbal stem cell deficiency(LSCD).METHODS:Ten patients(10 ... AIM:To evaluate the midterm outcomes of penetrating keratoplasty(PK)following allogeneic cultivated limbal epithelial transplantation(CLET)for bilateral total limbal stem cell deficiency(LSCD).METHODS:Ten patients(10 eyes)with bilateral LSCD were enrolled in this prospective noncomparative case series study.Each participant underwent PK approximately 6 mo after a CLET.Topical tacrolimus,topical and systemic steroids,and oral ciclosporin were administered postoperatively.Best-corrected visual acuity(BCVA),intraocular pressure(IOP),ocular surface grading scores(OSS),corneal graft epithelial rehabilitation,persistent epithelial defect(PED),immunological rejection,and graft survival rate were assessed.RESULTS:The time interval between PK and allogeneic CLET was 6.90±1.29(6-10)mo.BCVA improved from 2.46±0.32 log MAR preoperatively to 0.77±0.55 log MAR post-PK(P<0.001).Kaplan-Meier analysis of mean graft survival revealed graft survival rates of 100%at 12 and 24 mo and 80.0%at 36 mo.PEDs appeared in 5 eyes at different periods post-PK,and graft rejection occurred in 4 eyes.The total OSS decreased from 12.4±4.4 before allogeneic CLET to 1.4±1.51 after PK.CONCLUSION:A sequential therapy design of PK following allogeneic CLET can maintain a stable ocular surface with improved BCVA despite the relatively high graft rejection rate. 展开更多
关键词 limbal stem cell deficiency allogeneic cultured limbal epithelial transplantation penetrating keratoplasty graft rejection
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A narrative review of limbal stem cell deficiency&severe ocular surface disease
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作者 Jennifer C.W.Hu Danielle Trief 《Annals of Eye Science》 2023年第3期19-32,共14页
Background and Objective:Limbal stem cell deficiency(LSCD)describes the clinical condition when there is dysfunction of the corneal epithelial stem/progenitor cells and the inability to sustain the normal homeostasis ... Background and Objective:Limbal stem cell deficiency(LSCD)describes the clinical condition when there is dysfunction of the corneal epithelial stem/progenitor cells and the inability to sustain the normal homeostasis of the corneal epithelium.The limbal stem cells are located in a specialized area of the eye called the palisades of Vogt(POV).There have been significant advances in the diagnosis and management of LSCD over the past decade and this review focuses on the pathophysiology of LSCD,its clinical manifestations,diagnosis,and causes.Methods:Papers regarding LSCD were searched using PubMed to identify the current state of diagnosis and causes of LSCD published through to June 2022.Key Content and Findings:LSCD is clinically demonstrated by a whorl-epitheliopathy,loss of the POV,and conjunctivalization of the cornea.The diagnosis of this condition is based on clinical examination and aided by the use of impression cytology,in vivo confocal microscopy,and anterior segment optical coherence tomography(asOCT).There are many causes of LSCD,but those which are most common include chemical injuries,aniridia,contact lens wear,and Stevens-Johnson syndrome(SJS).Conclusions:While this condition is most commonly encountered by corneal specialists,it is important that other ophthalmologists recognize the possibility of LSCD as it may arise in other co-morbid eye conditions. 展开更多
关键词 limbal stem cell deficiency(LSCD) chemical injury contact lens ANIRIDIA
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Cell-based therapies for limbal stem cell deficiency: a literature review
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作者 Katherine Chen Mohammad Soleimani +3 位作者 Raghuram Koganti Kasra Cheraqpour Samer Habeel Ali R.Djalilian 《Annals of Eye Science》 2023年第2期14-25,共12页
Background and Objective:Limbal stem cell deficiency(LSCD)is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium.Severe cases of LSCD may be treated with limbal transplantation f... Background and Objective:Limbal stem cell deficiency(LSCD)is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium.Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue.Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants.In this review,we describe the success rates,and complications of different cell-based therapies for LSCD.We also discuss each therapy’s relative strengths and weaknesses,their history in animal and human studies,and their effectiveness compared to traditional transplants.Methods:PubMed was searched for publications using the terms LSCD,cell-based therapy,cultivated limbal epithelial transplantation(CLET),cultivated oral mucosal epithelial transplantation(COMET),and mesenchymal stem cells from 1989 to August 2022.Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.Key Content and Findings:current cell-based therapies for LSCD are CLET and non-limbal epithelial cells.Non-limbal epithelial cell methods include COMET,conjunctival epithelial autografts,and mesenchymal stem/stromal cells(MSCs).Moreover,several alternative potential sources of non-limbal cells have described,including induced pluripotent stem cells(iPSCs),human embryonic stem cells(hESCs),human dental pulp stem cells,hair follicle bulge-derived epithelial stem cells,amniotic membrane epithelial cells,and human umbilical cord lining epithelial cells.Conclusions:Cell-based therapies are a promising treatment modality for LSCD.While CLET is currently the only approved cell-based therapy and is only approved in the European Union,more novel methods have also been shown to be effective in human or animal studies thus far.Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure.iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated.Lastly,cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study.Several potential sources of non-limbal cells are under investigation. 展开更多
关键词 limbal stem cell deficiency(LSCD) cell-based therapy cultivated limbal epithelial transplantation(CLET) cultivated oral mucosal epithelial transplantation(COMET)
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Limbal stem cells: Central concepts of corneal epithelial homeostasis 被引量:12
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作者 Jinny J Yoon Salim Ismail Trevor Sherwin 《World Journal of Stem Cells》 SCIE CAS 2014年第4期391-403,共13页
A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferati... A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent stud-ies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal 展开更多
关键词 limbal stem cell CORNEAL EPITHELIUM XYZ HYPOTHESIS CORNEAL HOMEOSTASIS CORNEAL wound repair
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Quantification of corneal neovascularization after ex vivo limbal epithelial stem cell therapy 被引量:1
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作者 Adriano Guarnieri Javier Moreno-Monta?és +4 位作者 Belén Alfonso-Bartolozzi Alfonso L.Sabater María García-Guzmán Enrique J.Andreu Felipe Prosper 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2014年第6期988-995,共8页
AIM: To assess cultured limbal epithelial stem cell transplantation in patients with limbal stem cell deficiency by analyzing and quantifying corneal neovascularization.METHODS: This retrospective, interventional case... AIM: To assess cultured limbal epithelial stem cell transplantation in patients with limbal stem cell deficiency by analyzing and quantifying corneal neovascularization.METHODS: This retrospective, interventional case series included eight eyes with total limbal stem cell deficiency. Ex vivo limbal epithelial stem cells were cultured on human amniotic membrane using an animalfree culture method. The clinical parameters of limbal stem cell deficiency, impression cytology, and quantification of corneal neovascularization were evaluated before and after cultured limbal stem cell transplantation. The area of corneal neovascularization,vessel caliber(VC), and invasive area(IA) were analyzed before and after stem cell transplantation by image analysis software. Best-corrected visual acuity(BCVA),epithelial transparency, and impression cytology were also measured.RESULTS: One year after surgery, successful cases showed a reduction(improvement) of all three parameters of corneal neovascularization [neovascular area(NA), VC, IA], while failed cases did not. NA decreased a mean of 32.31%(P =0.035), invasion area29.37%(P =0.018) and VC 14.29%(P =0.072). BCVA improved in all eyes(mean follow-up, 76 ±21mo).Epithelial transparency improved significantly from 2.00 ±0.93 to 0.88±1.25(P =0.014). Impression cytology showed that three cases failed after limbal epithelial stem cell therapy before 1y of follow-up.CONCLUSION: This method of analyzing andmonitoring surface vessels is useful for evaluating the epithelial status during follow-up, as successful cases showed a bigger reduction in corneal neovascularization parameters than failed cases. Using this method,successful cases could be differentiated from failed cases. 展开更多
关键词 limbal stem cell corneal neovascularization stem cell therapy impression cytology limbal stem cell deficiency
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Limbal epithelial stem cells in corneal surface reconstruction
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作者 Li Wang Bowen Wang Hong Ouyang 《Annals of Eye Science》 2018年第1期14-21,共8页
Cornea serves as the partial front barrier and major light reflection organ of the eye.The integrity of corneal surface is essential for ocular function.Injuries or congenital diseases could significantly destruct the... Cornea serves as the partial front barrier and major light reflection organ of the eye.The integrity of corneal surface is essential for ocular function.Injuries or congenital diseases could significantly destruct the homeostasis of the ocular surface,especially the microenvironment of limbal epithelial stem cells(LESCs),and will eventually cause dysfunction of corneal regeneration and diminish of LESCs.The loss of LESCs by different reasons are named limbal stem cell deficiency(LSCD),which is one of the leading cause of vision loss worldwide.To restore the corneal surface,LESC transplantation in the form of tissue or cell cultures is currently a viable and promising method to treat LSCD.In this review,we aim to introduce the characters and niche of LESCs,and discuss different aspects of its application in cornea surface reconstruction. 展开更多
关键词 limbal epithelial stem cells(LESCs) CORNEA limbal stem cell deficiency(LSCD) stem cell transplantation
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Chronic ocular GVHD:limbal and conjunctival stem cell allografts from the same hematopoietic stem cell donor 被引量:2
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作者 Elias F Jarade Hala El Rami +1 位作者 Youssef Abdelmassih Mazen Amro 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第9期1569-1572,共4页
Dear Editor,I am Dr.Elias F Jarade from the Beirut Eye and ENT Specialist Hospital, Beirut, Lebanon. I write to describe a novel surgical technique in the management of chronic ocular graft-versus-host disease(GVHD).
关键词 Chronic ocular GVHD limbal and conjunctival stem cell allografts from the same hematopoietic stem cell donor
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Induced pluripotent stem cells as a potential therapeutic source for corneal epithelial stem cells 被引量:1
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作者 Jie Zhu Mark Slevin +1 位作者 Bao-Qiang Guo Shou-Rong Zhu 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第12期2004-2010,共7页
Corneal blindness caused by limbal stem cell deficiency(LSCD) is one of the most common debilitating eye disorders. Thus far, the most effective treatment for LSCD is corneal transplantation, which is often hindered b... Corneal blindness caused by limbal stem cell deficiency(LSCD) is one of the most common debilitating eye disorders. Thus far, the most effective treatment for LSCD is corneal transplantation, which is often hindered by the shortage of donors. Pluripotent stem cell technology including embryonic stem cells(ESCs) and induced pluripotent stem cells(iPSCs) have opened new avenues for treating this disease. iPSCs-derived corneal epithelial cells provide an autologous and unlimited source of cells for the treatment of LSCD. On the other hand, iPSCs of LSCD patients can be used for iPSCs-corneal disease model and new drug discovery. However, prior to clinical trial, the efficacy and safety of these cells in patients with LSCD should be proved. Here we focused on the current status of iPSCs-derived corneal epithelial cells used for cell therapy as well as for corneal disease modeling. The challenges and potential of iPSCs-derived corneal epithelial cells as a choice for clinical treatment in corneal disease were also discussed. 展开更多
关键词 induced pluripotent stem cells corneal epithelial cells limbal stem cell deficiency disease modeling
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Ocular stem cells:a narrative review of current clinical trials
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作者 Konstadinos Sotiropulos Dimitrios Kourkoutas +2 位作者 Diamantis Almaliotis Katherine Ploumidou Vasileios Karampatakis 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2022年第9期1529-1537,共9页
·Stem cells are undifferentiated cells showcasing a remarkable capacity of self-replenishing and differentiating into mature cells.Their ability to proliferate connotes that a designated stem cell source is capab... ·Stem cells are undifferentiated cells showcasing a remarkable capacity of self-replenishing and differentiating into mature cells.Their ability to proliferate connotes that a designated stem cell source is capable of generating an unrestricted number of mature cells.The ever-increasing comprehension of position,activity,and function of ocular stem cells has led to rapid progress and incessant improvement of possible procedures and therapies.A narrative review was conducted to summarize the current evidence on clinical trials and respective literature,regarding current evolution in the field of ocular regenerative medicine.We tried to ascertain the safety of experimental and clinical procedures,their effectiveness,and the ethical repercussion of their use. 展开更多
关键词 stem cells cell-based therapies limbal stem cells h ESC-derived retinal pigment epithelium human induced pluripotent stem cells olfactory mucosa mesenchymal stem cells
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Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance 被引量:6
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作者 John D West Natalie J Dorà J Martin Collinson 《World Journal of Stem Cells》 SCIE CAS 2015年第2期281-299,共19页
In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell(LESC)hypothesis is most widely accepted. This proposes that ste... In this review we evaluate evidence for three different hypotheses that explain how the corneal epithelium is maintained. The limbal epithelial stem cell(LESC)hypothesis is most widely accepted. This proposes that stem cells in the basal layer of the limbal epithelium, at the periphery of the cornea, maintain themselves and also produce transient(or transit) amplifying cells(TACs). TACs then move centripetally to the centre of the cornea in the basal layer of the corneal epithelium and also replenish cells in the overlying suprabasal layers. The LESCs maintain the corneal epithelium during normal homeostasis and become more active to repair significant wounds. Second, the corneal epithelial stem cell(CESC) hypothesis postulates that, during normal homeostasis, stem cells distributed throughout the basal corneal epithelium, maintain the tissue. According to this hypothesis, LESCs are present in the limbus but are only active during wound healing. We also consider a third possibility, that the corneal epithelium is maintained during normal homeostasis by proliferation of basal corneal epithelial cells without any input from stem cells. After reviewing the published evidence, we conclude that the LESC and CESC hypotheses are consistent with more of the evidence than the third hypothesis, so we do not consider this further. The LESC and CESC hypotheses each have difficulty accounting for one main type of evidence so we evaluate the two key lines of evidence that discriminate between them. Finally, we discuss how lineage-tracing experiments have begun to resolve the debate in favour of the LESC hypothesis. Nevertheless, it also seems likely that some basal corneal epithelial cells can act as long-term progenitors if limbal stem cell function is compromised. Thus, this aspect of the CESC hypothesis may have a lasting impact on our understanding of corneal epithelial maintenance, even if it is eventually shown that stem cells are restricted to the limbus as proposed by the LESC hypothesis. 展开更多
关键词 Eye CORNEA CORNEAL EPITHELIUM limbalepithelium stem cell LINEAGE tracing
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Corneal stem cells and tissue engineering: Current advances and future perspectives 被引量:4
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作者 Aline Lütz de Araujo JoséAlvaro Pereira Gomes 《World Journal of Stem Cells》 SCIE CAS 2015年第5期806-814,共9页
Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there aremany challeng... Major advances are currently being made in regenerative medicine for cornea. Stem cell-based therapies represent a novel strategy that may substitute conventional corneal transplantation, albeit there aremany challenges ahead given the singularities of each cellular layer of the cornea. This review recapitulates the current data on corneal epithelial stem cells, corneal stromal stem cells and corneal endothelial cell progenitors. Corneal limbal autografts containing epithelial stem cells have been transplanted in humans for more than 20 years with great successful rates, and researchers now focus on ex vivo cultures and other cell lineages to transplant to the ocular surface. A small population of cells in the corneal endothelium was recently reported to have self-renewal capacity, although they do not proliferate in vivo. Two main obstacles have hindered endothelial cell transplantation to date: culture protocols and cell delivery methods to the posterior cornea in vivo. Human corneal stromal stem cells have been identified shortly after the recognition of precursors of endothelial cells. Stromal stem cells may have the potential to provide a direct cell-based therapeutic approach when injected to corneal scars. Furthermore, they exhibit the ability to deposit organized connective tissue in vitro and may be useful in corneal stroma engineering in the future. Recent advances and future perspectives in the field are discussed. 展开更多
关键词 CORNEA stem cells cell-based therapy limbal TRANSPLANTATION TISSUE engineering Cornealendothelium
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Cryopreserved limbal lamellar keratoplasty for peripheral corneal and limbal reconstruction 被引量:1
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作者 Hua-Tao Xie Jing Li +3 位作者 Yang Liu Dong-Ling Jiang Rui-Fen Shen Ming-Chang Zhang 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2018年第4期699-702,共4页
This study aimed to evaluate the outcomes and described the recovery process of cryopreserved limbal lamellar keratoplasty(CLLK) for peripheral corneal and limbal diseases. Thirteen eyes of 12 patients with a mean a... This study aimed to evaluate the outcomes and described the recovery process of cryopreserved limbal lamellar keratoplasty(CLLK) for peripheral corneal and limbal diseases. Thirteen eyes of 12 patients with a mean age of 41±23.9 y were included. The average follow-up was 12.1±5.6 mo. Stable ocular surface was achieved in all eyes at last follow-up. Epithelialization originated from both recipient and graft in 9 eyes. We conclude that CLLK compensates for the shortage of donor corneas and cryopreserved limbal grafts provide epithelialization sources in ocular surface reconstruction. 展开更多
关键词 cryopreserve epithelialization lamellar keratoplasty limbus neovascularization ocular surface peripheral corneal and limbal diseases stem cells
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手术切除联合角膜缘干细胞移植治疗翼状胬肉的疗效观察
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作者 吴勤 杨春林 +1 位作者 陆瑶瑶 曹冬蕾 《中国临床新医学》 2024年第9期1026-1031,共6页
目的 观察手术切除联合角膜缘干细胞移植治疗翼状胬肉的疗效。方法 招募2020年1月至2022年12月启东市中医院收治的翼状胬肉患者180例,采用随机数字表法将其分为Ologen胶原基质植入组(接受手术切除联合Ologen胶原基质植入治疗,90例145眼... 目的 观察手术切除联合角膜缘干细胞移植治疗翼状胬肉的疗效。方法 招募2020年1月至2022年12月启东市中医院收治的翼状胬肉患者180例,采用随机数字表法将其分为Ologen胶原基质植入组(接受手术切除联合Ologen胶原基质植入治疗,90例145眼)和角膜缘干细胞移植组(接受手术切除联合角膜缘干细胞移植治疗,90例147眼)。比较两组治疗后屈光状态、泪膜功能、舒适度情况、创面愈合时间、临床疗效及复发情况。结果 两组术后裸眼视力(UCVA)、泪膜破裂时间(BUT)呈上升趋势,角膜散光度(CA)呈下降趋势,两组变化幅度差异有统计学意义(P<0.05)。在术后6个月,Ologen胶原基质植入组UCVA、BUT低于角膜缘干细胞移植组,CA高于角膜缘干细胞移植组,差异有统计学意义(P<0.05)。术后6个月,在畏光流泪、异物感、眼痛、球结膜充血4个维度,角膜缘干细胞移植组的舒适度评分显著优于Ologen胶原基质植入组(P<0.05)。角膜缘干细胞移植组的创面愈合时间显著快于Ologen胶原基质植入组[(2.85±1.06)d vs (3.04±0.31)d;t=2.073,P=0.039]。角膜缘干细胞移植组的临床有效率显著高于Ologen胶原基质植入组(98.64%vs 93.10%;χ^(2)=5.678,P=0.017),术后6个月的复发率更低(0.00%vs 4.14%;χ^(2)=4.325,P=0.038)。结论 手术切除联合角膜缘干细胞移植治疗翼状胬肉的疗效优于手术切除联合Ologen胶原基质植入治疗,值得推荐。 展开更多
关键词 Ologen胶原基质 角膜缘干细胞移植 翼状胬肉 屈光状态 翼状胬肉切除术
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退翳明目汤联合手术治疗翼状胬肉活动期的疗效观察
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作者 张婷 孙湛 郭宗宾 《中国中医眼科杂志》 2024年第4期342-345,354,共5页
目的 观察退翳明目汤联合手术治疗翼状胬肉的临床疗效。方法 纳入2018年6月—2021年6月宝鸡市中医医院诊治的翼状胬肉患者98例(98只眼),随机分为试验组和对照组,每组各49例(49只眼)。对照组以翼状胬肉切除联合自体角膜缘干细胞移植术治... 目的 观察退翳明目汤联合手术治疗翼状胬肉的临床疗效。方法 纳入2018年6月—2021年6月宝鸡市中医医院诊治的翼状胬肉患者98例(98只眼),随机分为试验组和对照组,每组各49例(49只眼)。对照组以翼状胬肉切除联合自体角膜缘干细胞移植术治疗。试验组在对照组的基础上联合退翳明目汤口服。2组均观察4周,分别于治疗前、后检查2组患者散光度数、角膜垂直曲率和水平曲率、泪膜破裂时间(BUT)、泪液分泌试验(SⅠT)。结果 2组治疗前散光度数、角膜垂直曲率和水平曲率、BUT、SⅠT比较,差异均无统计学意义(P>0.05)。(1)散光度数:2组治疗后散光度数均较治疗前降低,差异均有统计学意义(t_(试验组)=59.561、t_(对照组)=42.619,均P=0.000)。治疗后试验组散光度数低于对照组,差异有统计学意义(t=17.919,P=0.000)。(2)角膜垂直曲率:2组治疗后角膜垂直曲率均较治疗前升高,差异均有统计学意义(t_(试验组)=21.819、t_(对照组)=9.284,均P=0.000)。治疗后试验组角膜垂直曲率高于对照组,差异有统计学意义(t=13.831,P=0.000)。(3)角膜水平曲率:2组治疗后角膜水平曲率均较治疗前升高,差异均有统计学意义(t_(试验组)=21.052、t_(对照组)=15.903,均P=0.000)。治疗后试验组角膜水平曲率高于对照组,差异有统计学意义(t=11.241,P=0.000)。(4)BUT:2组治疗后BUT均较治疗前延长,差异均有统计学意义(t_(试验组)=14.672、t_(对照组)=8.537,均P=0.000)。治疗后,试验组BUT长于对照组,差异有统计学意义(t=5.015,P=0.000)。(5)SⅠT:2组治疗后SⅠT均较治疗前增加,差异均有统计学意义(t_(试验组)=7.781、t_(对照组)=5.426,均P=0.000)。治疗后2组间比较,差异无统计学意义(P>0.05)。(6)并发症发生率:试验组的并发症发生率低于对照组,差异有统计学意义(χ^(2)=4.782,P=0.029)。结论 退翳明目汤联合手术治疗翼状胬肉,有利于改善患者的泪膜功能,降低角膜散光度,同时降低并发症。 展开更多
关键词 退翳明目汤 散光度数 自体角膜缘 翼状胬肉
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