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cellular therapy of the corneal stroma: a new type of corneal surgery for keratoconus and corneal dystrophies

Eye and Vision 2018年第1期5卷 250-259页

作者： Jorge L.Aliódel Barrio Jorge L.Alió Cornea Cataract and Refractive Surgery UnitVissum CorporaciónAlicanteSpain Division of Ophthalmology Universidad Miguel HernándezAlicanteSpain. Vissum Instituto Oftalmologico de AlicanteAvda de Denia s/n03016 AlicanteSpain

cellular therapy of the corneal stroma,with either ocular or extraocular stem cells,has been gaining a lot of interest over the last *** publications from different research groups are showing its potential benefits in relation to its capacity to improve or alleviate corneal scars,improve corneal transparency in metabolic diseases by enhancing the catabolism of the accumulated molecules,generate new organized collagen within the host stroma,and its immunosuppressive and immunomodulatory *** extraocular stem cells do not require a healthy contralateral eye and they do not involve any ophthalmic procedures for their *** stem cells have been the most widely assayed and have the best potential to differentiate into functional adult keratocytes in vivo and in *** embryonic stem cells have been partially abandoned due to ethical implications,the discovery of the induced pluripotent stem cells(iPSC)has opened a new and very promising field for future research as they are pluripotent cells with the capacity to theoretically differentiate into any cell type,with the special advantage that they are obtained from adult differentiated *** delivery into the corneal stroma has been experimentally assayed in vivo in multiple ways:systemic versus local injections with or without a *** preliminary human clinical data is already available although still very limited,and further research is necessary in order to consolidate the clinical applications of this novel therapeutic line.

关键词： Stem cells Regenerative medicine Corneal transplant Decellularized cornea Cornea Corneal stroma cellular therapy MSC Mesenchymal stem cells

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Rationally designed monoamine oxidase A-activatable AIE molecular photosensitizer for the specific imaging and cellular therapy of tumors

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Aggregate 2023年第2期4卷 163-172页

作者： Yingcai Hu Sheng-Yan Yin Wei Liu Zuhao Li Yun Chen Jishan Li State Key Laboratory of Chemo/Bio-Sensing and Chemometrics College of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China

Due to both the requirements of repeated complex organic synthesis and tedious biochemical verification experiments for the screening of new photosensitizers,the development of a satisfactory photosensitizer with excellent photosensitivity and highly specific response ability is still a great challenge for the accurate imaging localization and the precise photodynamic therapy(PDT)of ***,under the help of theoretical calculations,a high-efficient target-activatable aggregation-induced emission(AIE)molecular photosensitizer,TPE-TThPy,is rationally designed and synthesized by the conjugation of tetraphenylethylene(TPE,which is used as the electron donor)and tetrahydropyridine(ThPy,which can be converted to methylpyridine salts as the electron acceptor)using thiophene(T)as the π-*** TPE-TThPy molecule exhibits not only good cellular uptake and mitochondrial targeting ability but also ultra-high monoamine oxidase A(MAO-A)response specificity and excellent photosensitivity when oxidized under the action of *** specifically imaging ability and cellular PDT performance of the MOA-A-activatable AIE photosensitizer of TPE-TThPy is demonstrated by using different cell lines and mouse tumor *** successful development of this MOA-A-activatable AIE photosensitizer also provides insight for the development of single-molecule PDT therapeutic drugs with excellent photosensitivity and highly specific targeting-response ability.

关键词： aggregation-induced emission cellular therapy fluorescence imaging photosensitizer target-activatable

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Is cellular therapy beneficial in management of rotator cuff tears?Meta-analysis of comparative clinical studies

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World Journal of Meta-Analysis 2022年第3期10卷 162-176页

作者： Sathish Muthu Cheruku Mogulesh Vibhu Krishnan Viswanathan Naveen Jeyaraman Satvik N Pai Madhan Jeyaraman Manish Khanna Department of Orthopaedics Government Medical College and HospitalDindigul 624001Tamil NaduIndia Department of Biotechnology School of Engineering and TechnologySharda UniversityGreater Noida 201306Uttar PradeshIndia Indian Stem Cell Study Group Association Lucknow 226010Uttar PradeshIndia Department of Orthopaedic Rheuamtology Dr Ram Manohar Lohiya National Law UniversityLucknow 226010Uttar PradeshIndia Department of MSK Oncology University of CalgaryAlberta AB T2N 1N4AlbertaCanada Department of Orthopaedics Atlas Hospitals(The Tamil Nadu Dr MGR Medical University)Tiruchirappalli 620002Tamil NaduIndia Department of Orthopaedics Sri Ramachandra Medical College and Research InstituteChennai 600116Tamil NaduIndia Department of Orthopaedics Faculty of MedicineSri Lalithambigai Medical College and HospitalDr MGR Educational and Research InstituteChennai 600095Tamil NaduIndia Department of Orthopaedics South Texas Orthopaedic Research Institute(STORI Inc.)LaredoTX 78045United States Department of Orthopaedics Autonomous State Medical CollegeAyodhya 224135Uttar PradeshIndia

BACKGROUND Mesenchymal stromal cell(MSC)-based cellular therapy promotes type I collagen production,enhance mechanical strength of tissues,and enhance biology at the bone-tendon interface,which primarily explains their potential clinical utility in rotator cuff(RC)*** To analyze the efficacy and safety of cellular therapy utilizing MSCs in the management of RC tears from clinical studies available in the *** We conducted independent and duplicate electronic database searches including PubMed,Embase,Reference Citation Anallysis,Web of Science,and Cochrane Library in August 2021 for studies analyzing the efficacy and safety of cellular therapy(CT)utilizing MSCs in the management of RC *** Analog Score(VAS)score for pain,American Shoulder and Elbow Surgeons(ASES)score,Disability of the Arm,Shoulder,and Hand score,Constant score,radiological assessment of healing,and complications such as retear rate and adverse events were the outcomes *** was performed in R-platform using OpenMeta[Analyst]*** Six studies involving 238 patients were included for *** noted a significant reduction in VAS score for pain at 3 mo(weighed mean difference[WMD]=-2.234,Pcellular therapy,as comp

关键词： Mesenchymal stromal cell Bone-marrow derived mesenchymal stromal cell Adipose-derived mesenchymal stromal cell Rotator cuff tear cellular therapy Meta-analysis

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Novel cellular therapies for hepatobiliary malignancies

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Hepatobiliary & Pancreatic Diseases International 2022年第5期21卷 450-454页

作者： Jing-Nan Xue Yan-Yu Wang Yun-Chao Wang Nan Zhang Long-Hao Zhang Zheng-Hui Lu Li-Jin Zhao Hai-Tao Zhao Department of Liver Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Hepatobiliary and Pancreatic Surgery Affiliated Hospital of Zunyi Medical UniversityZunyi 563000China Hepatobiliary and Pancreatic Surgery Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518000China

Background:The mortalities of hepatobiliary malignancies are *** the failure of conventional chemotherapy and unsatisfactory outcome of molecular targeted drugs,immune-based therapy has become a new focus of research in hepatobiliary cancers *** sources:We performed a Pub Med search with relevant articles published up to May 2022 and the following keywords:cellular immunotherapy,hepatobiliary cancer,antigen receptor T cell therapy,and receptor-engineered T *** of clinical trials was obtained from https://***/.Results:Cell therapies for hepatobiliary malignancies are at early stage of *** current review showed that cellular therapies are safe and feasible in *** findings provide an important platform for future lager scale clinical trials on immunotherapy in patients with hepatobiliary ***:With the continuous advances of cellular immunotherapy,the combination of cellular immunotherapy with surgery,chemotherapy and radiotherapy will be new therapeutic strategies for patients with hepatobiliary cancer.

关键词： cellular therapy Chimeric antigen receptor T cell therapy Receptor-engineered T cell Hepatobiliary malignancy

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cellular strategies to induce immune tolerance after liver transplantation:Clinical perspectives

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World Journal of Gastroenterology 2024年第13期30卷 1791-1800页

作者： Ai-Wei Zhou Jing Jin Yuan Liu Department of Liver Surgery Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Nursing Renji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China Department of Liver Transplantation Shanghai Immune Therapy InstituteShanghai 200127China

Liver transplantation(LT)has become the most efficient treatment for pediatric and adult end-stage liver disease and the survival time after transplantation is becoming longer due to the development of surgical techniques and perioperative ***,long-term side-effects of immunosuppressants,like infection,metabolic disorders and malignant tumor are gaining more *** tolerance is the status in which LT recipients no longer need to take any immunosuppressants,but the liver function and intrahepatic histology maintain *** approaches to achieve immune tolerance after transplantation include spontaneous,operational and induced *** first two means require no specific intervention but withdrawing immunosuppressant gradually during *** clinical factors or biomarkers so far could accurately predict who are suitable for immunosuppressant withdraw after *** the understanding to the underlying mechanisms of immune tolerance,many strategies have been developed to induce tolerance in LT *** strategy is one of the most promising methods for immune tolerance induction,including chimerism induced by hematopoietic stem cells and adoptive transfer of regulatory immune *** safety and efficacy of various cell products have been evaluated by prospective preclinical and clinical trials,while obstacles still exist before translating into clinical ***,we will summarize the latest perspectives and concerns on the clinical application of cellular strategies in LT recipients.

关键词： cellular therapy Induced tolerance Liver transplantation Regulatory T cells Regulatory dendritic cells

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CARs:a new approach for the treatment of autoimmune diseases

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Science China(Life Sciences) 2023年第4期66卷 711-728页

作者： Yeting Sun Yeshuang Yuan Bo Zhang Xuan Zhang Graduate School of Peking Union Medical College Department of RheumatologyBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineState Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China Department of Rheumatology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineClinical Immunology CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

The development of chimeric antigen receptor(CAR)-based therapeutic interventions represented a breakthrough in cancer *** the success of the CAR-T-cell strategy,this novel therapeutic approach has been applied to other diseases,including autoimmune *** CAR-T cells to deplete pathological immune cells(i.e.,B cells,autoreactive B or T cells,and accessory antigen-presenting cells(APCs))has resulted in favorable outcomes in diseases characterized by excessive autoantibody levels or hyperactive lymphocyte cell *** importance of immunosuppressive regulatory Tcells(Tregs)in restoring immune tolerance has been well established,and CAR-Tregs have shown promising therapeutic potential in treating autoimmune ***,prior experience from the cancer field has provided sufficient paradigms for understanding how to optimize the structure and function of CARs to improve their function,persistence,stability and *** this review,we describe the potential application of CAR-T cells and CAR-Tregs in the treatment of autoimmune diseases,and we summarize the currently available strategies of gene editing and synthetic biological tools that have improved the practical application of CAR-based therapies.

关键词： autoimmune diseases chimeric antigen receptor regulatory T cells cellular therapy

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Implantation of human umbilical cord mesenchymal stem cells for ischemic stroke： perspectives and challenges

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Frontiers of Medicine 2015年第1期9卷 20-29页

作者： Yingchen Li Guoheng Hu Qilai Chen Post_Graduate School Hunan University of Traditional Chinese Medicine Changsha 410208 China Department of Neurology The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine Changsha 410007 China

lschemic stroke is a focal cerebral insult that often leads to many adverse neurological complications severely affecting the quality of life. The prevalence of stroke is increasing throughout the world, while the efficacy of current pharmacological therapies remains unclear. As a neuroregenerative therapy, the implantation of human umbilical cord mesenchymal stem cells （hUC-MSCs） has shown great possibility to restore function after stroke. This review article provides an update role of hUC-MSCs implantation in the treatment of ischemic stroke. With the unique ＂immunosuppressive and immunoprivilege＂ property, hUC-MSCs are advised to be an important candidate for aUogeneic cell treatment. Nevertheless, most of the treatments are still at primary stage and not clinically feasible at the current time. Several uncertain problems, such as culture conditions, allograft rejection, and potential tumorigenicity, are the choke points in this cellular therapy. More preclinical researches and clinical studies are needed before hUC-MSCs implantation can be used as a routinely applied clinical therapy.

关键词： human umbilical cord mesenchymal stem cells ischemic stroke cellular therapy transplantation

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Chondrogenic potential of mesenchymal stem cells from horses using a magnetic 3D cell culture system

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World Journal of Stem Cells 2021年第6期13卷 645-658页

作者： Joice Fülber Fernanda R Agreste Sarah R T Seidel Eric D P Sotelo Ângela P Barbosa Yara M Michelacci Raquel Y A Baccarin Departamento de Clínica Médica Medicina Veterinária e ZootecniaUniversidade de São PauloSão Paulo 05506-270Brazil Departamento de Bioquímica Escola Paulista de MedicinaUniversidade Federal de São PauloSão Paulo 04044-020Brazil

BACKGROUND Mesenchymal stem cells(MSCs)represent a promising therapy for the treatment of equine joint diseases,studied due to their possible immunomodulatory characteristics and regenerative ***,the source of most suitable MSCs for producing cartilage for regenerative processes in conjunction with biomaterials for an enhanced function is yet to be *** To compare the chondrogenicity of MSCs derived from synovial fluid,bone marrow,and adipose tissue of horses,using the aggrecan *** MSCs from ten horses were cultured,phenotypic characterization was done with antibodies CD90,CD44 and CD34 and were differentiated into *** 3D cell culture system in which biocompatible nanoparticles consisting of gold,iron oxide,and poly-L-lysine were added to the cells,and they were forced by magnets to form one *** microspheroids were exposed to a commercial culture medium for 4 d,7 d,14 d,and 21 *** extraction was performed,and aggrecan was quantified by enzyme-linked immunosorbent *** sulfate and aggrecan in the microspheroids were identified and localized by *** All cultured cells showed fibroblast-like appearance,the ability to adhere to the plastic surface,and were positive for CD44 and CD90,thus confirming the characteristics and morphology of *** soluble protein concentrations were higher in the microspheroids derived from adipose *** aggrecan concentration and the ratio of aggrecan to soluble proteins were higher in microspheroids derived from synovial fluid than in those derived from bone marrow,thereby showing chondrogenic *** from all sources expressed aggrecan and keratan sulfate when observed using confocal immunofluorescence *** sources of MSCs can synthesize aggrecan,however,MSCs from synovial fluid and adipose tissue have demonstrated better biocompatibility in a 3D environment,thus suggesting chondrogenic superiority

关键词： cellular therapy Chondrocytes Aggrecan Keratan sulfate

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Neural stem cell therapy for brain disease

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World Journal of Stem Cells 2021年第9期13卷 1278-1292页

作者： Lan Zhao Jian-Wei Liu Hui-Yan Shi Ya-Min Ma First Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300381China National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion Tianjin 300381China Tianjin University of Traditional Chinese Medicine Tianjin 301617China

Brain diseases, including brain tumors, neurodegenerative disorders, cerebrovasculardiseases, and traumatic brain injuries, are among the major disordersinfluencing human health, currently with no effective therapy. Due to the lowregeneration capacity of neurons, insufficient secretion of neurotrophic factors,and the aggravation of ischemia and hypoxia after nerve injury, irreversible lossof functional neurons and nerve tissue damage occurs. This damage is difficult torepair and regenerate the central nervous system after injury. Neural stem cells(NSCs) are pluripotent stem cells that only exist in the central nervous *** have good self-renewal potential and ability to differentiate into neurons,astrocytes, and oligodendrocytes and improve the cellular *** transplantation approaches have been made for various neurodegenerativedisorders based on their regenerative potential. This review summarizes anddiscusses the characteristics of NSCs, and the advantages and effects of NSCs inthe treatment of brain diseases and limitations of NSC transplantation that need tobe addressed for the treatment of brain diseases in the future.

关键词： Neural stem cell Brain disease therapy Animal experiment Clinical trial cellular therapy

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Stem cell homing, tracking and therapeutic efficiency evaluation for stroke treatment using nanoparticles: A systematic review

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World Journal of Stem Cells 2020年第5期12卷 381-405页

作者： Mariana Penteado Nucci Igor Salerno Filgueiras Joao Matias Ferreira Fernando Anselmo de Oliveira Leopoldo Penteado Nucci Javier Bustamante Mamani Gabriel Nery Albuquerque Rego Lionel Fernel Gamarra LIM44 Hospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de Sao PauloSao Paulo 05529-060Brazil Hospital Israelita Albert Einstein Sao Paulo 05529-060Brazil Centro Universitário do Planalto Central BrasíliaDFBrazil

BACKGROUND Stroke is the second leading cause of death *** is a real need to develop treatment strategies for reducing neurological deficits in stroke survivors,and stem cell(SC)therapeutics appear to be a promising alternative for stroke therapy that can be used in combination with approved thrombolytic or thrombectomy ***,the efficacy of SC therapy depends on the SC homing ability and engraftment into the injury site over a long period of ***,tracking SCs from their niche to the target tissues is a complex *** To evaluate SC migration homing,tracking and therapeutic efficacy in the treatment of stroke using nanoparticles METHODS A systematic literature search was performed to identify articles published prior to November 2019 that were indexed in PubMed and *** following inclusion criteria were used:(1)Studies that used in vivo models of stroke or ischemic brain lesions;(2)Studies of SCs labeled with some type of contrast agent for cell migration detection;and(3)Studies that involved in vivo cellular homing and tracking *** A total of 82 articles were identified by indexing in Scopus and Pub *** inclusion criteria were applied,35 studies were selected,and the articles were assessed for eligibility;ultimately,only 25 studies were *** of the selected studies used SCs from human and mouse bone marrow labeled with magnetic nanoparticles alone or combined with fluorophore *** cells were administered in the stroke model(to treat middle cerebral artery occlusion in 74%of studies and for photothrombotic induction in 26%of studies).Fiftythree percent of studies used xenogeneic grafts for cell therapy,and the migration homing and tracking evaluation was performed by magnetic resonance imaging as well as other techniques,such as near-infrared fluorescence imaging(12%)or bioluminescence assays(12%).CONCLUSION Our systematic review provided an up-to-date evaluation of SC migration hom

关键词： Stem cell Nanoparticles Homing Tracking Near-infrared fluorescence image cellular therapy Magnetic resonance image Bioluminescence Stroke

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