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mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation for ferroptosis after spinal cord injury

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Neural Regeneration Research 2023年第9期18卷 1861-1868页

作者： Qi-Feng Song Qian Cui Ya-Shi Wang Li-Xin Zhang Department of Rehabilitation Shengjing Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Spinal cord injury is characte rized by diffe rent aetiologies,complex pathogenesis,and diverse pathological changes.Current treatments are not ideal,and prognosis is generally poor.After spinal cord injury,neurons die due to various forms of cell death.Among them,fe rroptosis causes dysfunction after spinal cord injury,and no existing traditional treatments have been indicated to block its occurrence.Meanwhile,emerging therapies using mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation therapy are promising for reve rsing spinal co rd neuronal ferroptosis after spinal cord injury.However,no definitive studies have demonstrated the effectiveness of these approaches.This review summarizes the existing research on the mechanisms of ferroptosis;fe rroptosis after spinal cord injury;treatment of spinal cord injury with mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation;and treatment of ferroptosis using mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation.Inhibiting ferroptosis can promote the reversal of neurological dysfunction after spinal cord injury.In addition,mesenchymal stem cells,extracellular vesicles,and transc ranial magnetic stimulation can reve rse adverse outcomes of spinal cord injury and regulate ferroptosis-related fa ctors.Thus,it can be inferred that mesenchymal stem cells,extracellular vesicles,and transcranial magnetic stimulation have the potential to inhibit fe rroptosis after spinal cord injury.This review serves as a reference for future research to confirm these conclusions.

关键词： exosomes extracellular vesicles ferroptosis iron overload lipid peroxidation mesenchymal stem cells miRNAs spinal cord injury stem cells transcranial magnetic stimulation

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mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes

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World Journal of stem cells 2024年第5期16卷 467-478页

作者： Mazhar Mushtaq Doaa Hussein Zineldeen Muhammad Abdul Mateen Khawaja Husnain Haider Department of Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia Medical Biochemistry and Molecular Biology Department Faculty of MedicineTanta UniversityTanta 6632110Egypt

Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal regeneration.However,structural and functional recovery is a senile process involving multifaceted cellular and molecular processes.The contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large gap.Recent advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic PNI.The recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

关键词： Exosome mesenchymal stem cells Nerve injury stem cells Secretome Regeneration

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mesenchymal stem cells,the secretome and biomaterials:Regenerative medicine application

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BIOCELL 2022年第10期46卷 2201-2208页

作者： KI-TAEK LIM TEJAL V.PATIL DINESH KPATEL SAYAN DEB DUTTA KEYA GANGULY AAYUSHI RANDHAWA Department of Biosystems Engineering Interdisciplinary Program in Smart AgricultureKangwon National UniversityChuncheon341Korea

mesenchymal stem cells(MSCs)are multipotent cells usually isolated from bone marrow,endometrium,adipose tissues,skin,and dental pulp.MSCs played a crucial role in regenerative therapy and have been introduced as an interdisciplinary field between cell biology and material science.Recently,MSCs have been widely explored for their application in regenerative medicine and COVID-19 treatment.Different approaches to evaluate the future of biomaterials and stem cell properties have been developed.However,misconceptions and ethical issues still exist,such as MSCs being non-angiogenic,anti-apoptotic,and immunoregulatory competencies.Embryonic stem cells isolation primarily requires the consent of donors and can include the killing of fertilized eggs.These issues generate questions related to ethical and moral issues.However,MSCs have gained considerable attention for tissue regeneration owing to their differentiation ability with immunomodulatory effects.They are capable of secreting a broad range of biomolecules such as proteins,nucleic acids,exosomes,microRNAs,and membrane vesicles,collectively known as secretomes.Secretomes are released in response to the surrounding microenvironment.In this article,we briefly address topics related to the therapeutic potential of MSCs as an advanced approach in the field of regenerative medicine and various perspectives.

关键词： mesenchymal stem cells Secretome Biomaterials Regenerative Medicine

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mesenchymal stem cells,secretome and biomaterials in in-vivo animal models:Regenerative medicine application in cutaneous wound healing

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BIOCELL 2022年第8期46卷 1815-1826页

作者： MASSIMO CONESE AURELIO PORTINCASA Department of Medical and Surgical Sciences University of FoggiaFoggia71122Italy Department of Clinical and Experimental Medicine University of FoggiaFoggia71122Italy

The treatment of nonhealing and chronic cutaneous wounds still needs a clinical advancement to be effective.Both mesenchymal stem cells(MSCs),obtained from different sources,and their secretome derived thereof(especially exosomes)can activate signaling pathways related to promotion of cell migration,vascularization,collagen deposition,and inflammatory response demonstrating prohealing,angiogenetic and anti-scarring capacities.On the other hand,biodegradable biomimetic scaffolds can facilitate endogenous cell attachment and proliferation as well as extracellular matrix production.In this Review,we revise the complex composites made by biomimetic scaffolds,mainly hydrogels,and MSC-derived exosomes constructed for cutaneous wound healing.Studies demonstrate that there exists a synergistic action of scaffolds with encapsulated exosomes,displaying a sustained release profiles to facilitate longlasting healing effects.It can be envisioned that dressings made by biomimetic hydrogels and MSC-derived exosomes will be clinically applied in the near future for the effective treatment of nonhealing and chronic wounds.

关键词： Biomimetic scaffolds Cutaneous wound healing Exosomes Hydrogels mesenchymal stem cells Secretome

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mesenchymal stem cells and cell-free preparations for treating atopic dermatitis

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BIOCELL 2022年第11期46卷 2363-2367页

作者： TRINIDAD MONTERO-VILCHEZ MANUEL SANCHEZ-DIAZ CAROLINA MONTERO-VILCHEZ ALVARO SIERRA-SANCHEZ SALVADOR ARIAS-SANTIAGO Dermatology Department Virgen de las Nieves University HospitalGranadaSpain Instituto de Investigación Biosanitaria Granada GranadaSpain Pharmacy Department Virgen de las Nieves University HospitalGranadaSpain Dermatology Department Faculty of MedicineUniversity of GranadaGranadaSpain

Atopic dermatitis(AD)is a chronic cutaneous inflammatory disease caused by an interaction between genetic,immune and epidermal barrier factors.Several treatments can be used to treat this disease but there are patients that do not respond to actual drugs.So,there is a need to develop effective therapies for AD.mesenchymal stem cells(MSCs)are non-hematopoietic multipotent adult progenitor cells with immunomodulatory power and self-regenerating capacity to repair tissue damage,so they could be a potential effective treatment for AD.MSCs-Conditioned Medium(CM)and MSCs-exosomes are cell-free preparation with molecules secreted by stem cells that could be also beneficial for AD.This viewpoint reviews the actual development of MSCs,MSCs-CM and MSCs-exosomes for treating patients with AD.

关键词： Atopic dermatitis Conditioned medium Dermatology mesenchymal stem cells stem cells

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mesenchymal stem cells-derived extracellular vesicles as‘natural’drug delivery system for tissue regeneration

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BIOCELL 2022年第4期46卷 899-902页

作者： KENJI TSUJI SHINJI KITAMURA JUN WADA Department of Nephrology RheumatologyEndocrinology and MetabolismOkayama University Academic Field of MedicineDentistry and Pharmaceutical SciencesOkayama700-8558Japan

mesenchymal stem cells(MSCs)have abilities to mediate tissue protection through mechanisms of antiapoptosis,anti-oxidative stress and anti-fibrosis as well as tissue regeneration through mechanisms of cell proliferation,differentiation and angiogenesis.These effects by MSCs are mediated by a variety of factors,including growth factors,cytokines and extracellular vesicles(EVs).Among these factors,EVs,containing proteins,mRNA and microRNAs(miRNA),may carry their contents into distant tissues with high stability.Therefore,the treatment with MSC-derived EVs may be promising as‘natural’drug delivery systems(DDS).Especially,the treatment of MSCderived EVs with the manipulation of specific miRNAs expression has been reported to be beneficial under a variety of diseases and tissue injuries.The overexpression of specific miRNAs in the EVs might be through pre-loading method using the gene editing system by plasmid vector or post-loading method to load miRNA mimics into EVs by electroporation or calcium chloride-mediated transfection.Despite current several challenges for clinical use,it should open the next era of regenerative medicine for a variety of diseases.In this article,we highlight the therapeutic potential of MSC-derived EVs as‘natural’DDS and current challenges.

关键词： mesenchymal stem cells Extracellular vesicles Drug delivery system microRNA Regeneration

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mesenchymal stem cells from different sources and their derived exosomes: A pre-clinical perspective

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World Journal of stem cells 2020年第2期12卷 100-109页

作者： María álvarez-Viejo Unidad de Terapia Celulary Medicina Regenerativa Servicio de Hematologíay Hemoterapia Hospital Universitario Central de Asturias Plataforma de Terapias Avanzadas Instituto de Investigación Sanitaria del Principado de Asturias

Since the introduction of cell therapy as a strategy for the treatment of many diseases,mesenchymal stem cells have emerged as ideal candidates,yet the underlying mechanisms of their beneficial effects are only partially understood.At the start of the 21st century,a paracrine effect was proposed as a mechanism of tissue repair by these cells.In addition,a role was suggested for a heterogeneous population of extracellular vesicles in cell-to-cell communication.Some of these vesicles including exosomes have been isolated from most fluids and cells,as well as from supernatants of in vitro cell cultures.Recent research in the field of regenerative medicine suggests that exosomes derived from mesenchymal stem cells could be a powerful new therapeutic tool.This review examines the therapeutic potential of these exosomes obtained from the sources most used in cell therapy:bone marrow,adipose tissue,and umbilical cord.

关键词： mesenchymal stem cells Exosomes Cellular therapy

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mesenchymal stem cells ameliorate B-cell-mediated immune responses and increase IL-10-expressing regulatory B cells in an EBI3-dependent manner

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Cellular & Molecular Immunology 2017年第11期14卷 895-908页

作者： Kyung-Ah Cho Jun-Kyu Lee Yu-Hee Kim Minhwa Park So-Youn Woo Kyung-Ha Ryu Department of Microbiology School of MedicineEwha Womans UniversitySeoul 07985Republic of Korea Department of Pediatrics School of MedicineEwha Womans UniversitySeoul 07985Republic of Korea

Effector B cells are central contributors to the development of autoimmune disease by activating autoreactive T cells,producing pro-inflammatory cytokines and organizing ectopic lymphoid tissue.Conversely,IL-10-producing regulatory B(Breg)cells have pivotal roles in maintaining immunological tolerance and restraining excessive inflammation in autoinflammatory disease.Thus,regulating the equilibrium between antibody-producing effector B cells and Breg cells is critical for the treatment of autoimmune disease.In this study,we investigated the effect of human palatine tonsil-derived mesenchymal stem cells(T-MSCs)on estradiol(E2)-induced B-cell responses in vivo and in vitro.Transplantation of T-MSC into E2-treated mice alleviated B-cell-mediated immune responses and increased the population of IL-10-producing Breg cells.T-MSCs regulated the B-cell populations by producing Epstein–Barr virus(EBV)-induced 3(EBI3),one of the two subunits of IL-35 that is the well-known inducer of Breg cells.We demonstrate a critical role of EBI3(IL-35)in vitro by depleting EBI3 in T-MSCs and by adding exogenous IL-35 to the culture system.Taken together,our data suggest that IL-35-secreting MSCs may become an attractive therapeutic to treat B-cell-mediated autoimmune diseases via expanding Breg cells.

关键词： autoimmune disease B cells IL-35 mesenchymal stem cells

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mesenchymal stem cells in ischemic tissue regeneration

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World Journal of stem cells 2023年第2期15卷 16-30页

作者： Renata Szydlak Medical Biochemistry Faculty of Medicine Jagiellonian UniversityMedical College Kraków 31-034 Poland

Diseases caused by ischemia are one of the leading causes of death in the world.Current therapies for treating acute myocardial infarction,ischemic stroke,and critical limb ischemia do not complete recovery.Regenerative therapies opens new therapeutic strategy in the treatment of ischemic disorders.mesenchymal stem cells(MSCs)are the most promising option in the field of cell-based therapies,due to their secretory and immunomodulatory abilities,that contribute to ease inflammation and promote the regeneration of damaged tissues.This review presents the current knowledge of the mechanisms of action of MSCs and their therapeutic effects in the treatment of ischemic diseases,described on the basis of data from in vitro experiments and preclinical animal studies,and also summarize the effects of using these cells in clinical trial settings.Since the obtained therapeutic benefits are not always satisfactory,approaches aimed at enhancing the effect of MSCs in regenerative therapies are presented at the end.

关键词： Ischemia mesenchymal stem cells Regenerative medicine stem cell therapy Clinical applications

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mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer:A review

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World Journal of Diabetes 2023年第11期14卷 1585-1602页

作者： Hong-Min Zhang Meng-Liu Yang Jia-Zhuang Xi Gang-Yi Yang Qi-Nan Wu Department of Endocrinology People’s Hospital of Chongqing Liangjiang New AreaChongqing 400030China Department of Endocrinology The Second Affiliated Hospital of The Chongqing Medical UniversityChongqing 400030China Department of Endocrinology Dazu Hospital of Chongqing Medical UniversityThe People’s Hospital of DazuChongqing 406230China

The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

关键词： Diabetic foot ulcer mesenchymal stem cells Drug delivery systems Diabetes Wound healing

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