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mesenchymal stem cell-derived exosomes promote neurogenesis and cognitive function recovery in a mouse model of Alzheimer’s disease

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Neural Regeneration Research 2019年第9期14卷 1626-1634页

作者： Edwin E. Reza-Zaldivar Mercedes A. Hernández-Sapiéns Yanet K. Gutiérrez-Mercado Sergio Sandoval-ávila Ulises Gomez-Pinedo Ana L. Márquez-Aguirre Estefanía Vázquez-Méndez Eduardo Padilla-Camberos Alejandro A. Canales-Aguirre Unidad de Evaluation Preclinica Unidad de Biotecnologia Medica y FarmaceuticaCentro de Investigation y Asistencia en Tecnologia y Diseno del Estado de JaliscoGuadalajaraMexico Regenerative Medicine Unit Neuroscience InstituteDepartment of Neurosurgery and NeurologyIdlSSC Health Research Institute of the Hospital Clinico San CarlosMadridSpain

Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.

关键词： Alzheimer’s disease neurodegenerative disease cognitive impairment memory Alzheimer’s disease mouse model mesenchymal stem cell exosomes neurogenesis cognitive improvement cell-free therapy neural regeneration

mesenchymal stem cells and the neuronal microenvironment in the area of spinal cord injury

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Neural Regeneration Research 2019年第2期14卷 227-237页

作者： Yana O.Mukhamedshina Olga A.Gracheva Dina M.Mukhutdinova Yurii A.Chelyshev Albert A.Rizvanov OpenLab Gene and Cell Technologies Institute of Fundamental Medicine and Biology Kazan (Volga Region)Federal University Department of Histology Cytology and Embryology Kazan State Medical University Department of Therapy and Clinical Diagnostics with radiology Faculty of Veterinary Medicine Bauman Kazan State Academy of Veterinary Medicine OpenLab Gene and Cell Technologies Institute of Fundamental Medicine and Biology Kazan (Volga Region) Federal University

Cell-based technologies are used as a therapeutic strategy in spinal cord injury(SCI). mesenchymal stem cells(MSCs), which secrete various neurotrophic factors and cytokines, have immunomodulatory, anti-apoptotic and anti-inflammatory effects, modulate reactivity/phenotype of astrocytes and the microglia, thereby promoting neuroregeneration seem to be the most promising. The therapeutic effect of MSCs is due to a paracrine mechanism of their action, therefore the survival of MSCs and their secretory phenotype is of particular importance. Nevertheless, these data are not always reported in efficacy studies of MSC therapy in SCI. Here, we provide a review with summaries of preclinical trials data evaluating the efficacy of MSCs in animal models of SCI. Based on the data collected, we have tried(1) to establish the behavior of MSCs after transplantation in SCI with an evaluation of cell survival, migration potential, distribution in the area of injured and intact tissue and possible differentiation;(2) to determine the effects MSCs on neuronal microenvironment and correlate them with the efficacy of functional recovery in SCI;(3) to ascertain the conditions under which MSCs demonstrate their best survival and greatest efficacy.

关键词： spinal cord injury mesenchymal stem cells survival migration Rho/ROCK/PTEN astrocytes microglia myelin-forming cells axon growth tissue integrity

The short-chain perfluorinated compounds PFBS,PFHxS, PFBA and PFHxA, disrupt human mesenchymal stem cell self-renewal and adipogenic differentiation

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Journal of Environmental Sciences 2020年第2期32卷 187-199页

作者： Shuyu Liu Renjun Yang Nuoya Yin Francesco Faiola State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China College of Resources and Environment University of Chinese Academy of SciencesBeijing 100049China Wellcome Trust/CRUK Gurdon Institute Department of PathologyUniversity of CambridgeCambridge CB21QNUK

Per-and polyfluorinated alkyl substances(PFASs) are commonly used in industrial processes and daily life products.Because they are persistent, they accumulate in the environment, wildlife and humans.Although many studies have focused on two of the most representative PFASs, PFOS and PFOA, the potential toxicity of short-chain PFASs has not yet been given sufficient attention.We used a battery of assays to evaluate the toxicity of several four-carbon and six-carbon perfluorinated sulfonates and carboxyl acids(PFBS,PFHxS, PFBA and PFHxA), with a human mesenchymal stem cell(hMSC) system.Our results demonstrate significant cyto-and potential developmental toxicity for all the compounds analyzed, with shared but also distinct mechanisms of toxicity.Moreover, the effects of PFBS and PFHxS were stronger than those of PFBA and PFHxA, but occurred at higher doses compared to PFOS or PFOA.

关键词： Short-chain perfluorinated compounds Human mesenchymal stem cells(hMSCs) Adipogenesis/osteogenesis Developmental toxicity PFBS/PFBA/PFHxS/PFHxA

Clinical and imaging features of phosphaturic mesenchymal tumors

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Chinese Medical Journal 2023年第3期136卷 351-353页

作者： Cheng Chang Aihong Yu Yuhua You Xiaoxin Peng Xiaoguang Cheng Xintong Li Wei Liang Lihua Gong Wei Deng Department of Radiology Beijing Jishuitan Hospitalthe 4th Medical College of Peking UniversityBeijing 100035China Department of Radiology Beijing Anding HospitalCapital Medical UniversityBeijing 100088China The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders Beijing 100088China Department of Pathology Beijing Jishuitan Hospitalthe 4th Medical College of Peking UniversityBeijing 100035China Department of Endocrinology Beijing Jishuitan Hospitalthe 4th Medical College of Peking UniversityBeijing 100035China

To the Editor:Phosphaturic mesenchymal tumor(PMT)is a rare,slowly progressive,histomorphologically distinct entity of tumors that can emerge anywhere in the body.[1]According to World Health Organization,PMT has two pathological types:benign and malignant.[2]PMT was discovered due to tumor-induced osteomalacia(TIO)and is increasingly accepted in recent years as the leading cause of TIO.[1]However,most published reports have focused on the clinicopathological,immunohistochemical,and molecular genetic studies on PMT rather than the radiological work-ups.[3,4]Hence,the aim of this study was to find the common imaging characteristics of PMT to assist clinical diagnosis.

关键词： tumors mesenchymal tumor

mesenchymal stem cells, implications for pain therapy

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Neural Regeneration Research 2019年第11期14卷 1915-1916页

作者： Elena Trallori Carla Ghelardini Lorenzo Di Cesare Mannelli Dipartimento di Neuroscienze Psicologia Area del Farmaco e Salute del Bambino-Neurofarba-Sezione di Farmacologia e Tossicologia Università degli Studi di Firenze

History and biology of mesenchymal stem cell (MSC): MSCs were firstly described around 1970s by Friedenstein and his collaborators as a subpopulation of colony forming, clonogenic, plastic adherent stromal bone marrow derived cells, with the capacity to regenerate other tissues (Murphy et al., 2013). Caplan (1991) proposed that these mesenchymal cells were “stem” because of their ability to differentiate to any lineage of mesodermal cells. The richest sources of MSCs are bone marrow and adipose tissue, but they can also be isolated from synovial fluid, periosteum, fetal organs, placenta, umbilical cord blood and amniotic fluid (Murphy et al., 2013;Sherman et al., 2015).

关键词： mesenchymal stem cell (MSC) implications pain therapy

Bone marrow-derived mesenchymal stem cell transplantation attenuates overexpression of inflammatory mediators in rat brain after cardiopulmonary resuscitation

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Neural Regeneration Research 2020年第2期15卷 324-331页

作者： Qing-Ming Lin Xia-Hong Tang Shi-Rong Lin Ben-Dun Chen Feng Chen Institute of Fujian Emergency Medicine Clinical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFujian Provincial Emergency CenterFuzhouFujian ProvinceChina

Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopul

关键词： antibody array asphyxia brain damage cardiac arrest cardiopulmonary resuscitation global cerebral ischemia inflammatory mediator mesenchymal stem cell neurological deficit score S100B

Protective effect of thodioloside and bone marrow mesenchymal stem cells infected with HIF-1-expressing adenovirus on acute spinal cord injury

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Neural Regeneration Research 2020年第4期15卷 690-696页

作者： Xiao-Qin Ha Bo Yang Huai-Jing Hou Xiao-Ling Cai Wan-Yuan Xiong Xu-Pan Wei Lanzhou University Second Hospital LanzhouGansu ProvinceChina Department of Clinical Laboratory Lanzhou General Hospital of Lanzhou Military Area CommandLanzhouGansu ProvinceChina School of Clinical Medicine Gansu University of Traditional Chinese MedicineLanzhouGansu ProvinceChina School of Life Science and Engineering Lanzhou University of TechnologyLanzhouGansu ProvinceChina

Rhodioloside has been shown to protect cells from hypoxia injury,and bone marrow mesenchymal stem cells have a good effect on tissue repair.To study the effects of rhodioloside and bone marrow mesenchymal stem cells on spinal cord injury,a rat model of spinal cord injury was established using the Infinite Horizons method.After establishing the model,the rats were randomly divided into five groups.Rats in the control group were intragastrically injected with phosphate buffered saline(PBS)(5μL).PBS was injected at 6 equidistant points around 5 mm from the injury site and at a depth of 5 mm.Rats in the rhodioloside group were intragastrically injected with rhodioloside(5 g/kg)and intramuscularly injected with PBS.Rats in the mesenchymal stem cell(MSC)group were intramuscularly injected with PBS and intramuscularly with MSCs(8×10^6/mL in a 50-μL cell suspension).Rats in the Ad-HIF-MSC group were intragastrically injected with PBS and intramuscularly injected with HIF-1 adenovirus-infected MSCs.Rats in the rhodioloside+Ad-HIF-MSC group were intramuscularly injected with MSCs infected with the HIF-1 adenovirus and intragastrically injected with rhodioloside.One week after treatment,exercise recovery was evaluated with a modified combined behavioral score scale.Hematoxylin-eosin staining and Pischingert’s methylene blue staining were used to detect any histological or pathological changes in spinal cord tissue.Levels of adenovirus IX and Sry mRNA were detected by real-time quantitative polymerase chain reaction and used to determine the number of adenovirus and mesenchymal stem cells that were transfected into the spinal cord.Immunohistochemical staining was applied to detect HIF-1 protein levels in the spinal cord.The results showed that:(1)compared with the other groups,the rhodioloside+Ad-HIF-MSC group exhibited the highest combined behavioral score(P<0.05),the most recovered tissue,and the greatest number of neurons,as indicated by Pischingert’s methylene blue staining.(2)Compared with the PBS group,HIF-1 protein ex

关键词： acute spinal cord injury adenovirus adenovirus gene IX bone marrow mesenchymal stem cells combined behavioral score scale HIF-1α nerve regeneration nerve repair Rhodiola rosea Sry

Micropillar-arrayed surfaces promote transforming growth factor beta 1 induced epithelial to mesenchymal transition by focal adhesion kinase-related signaling in A549 cells

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Chinese Medical Journal 2021年第6期134卷 754-756页

作者： Lun-Kun Ma Xing Wang Xiao-Li Xu Jin Zhou Yi Liao Jian-Guo Feng Li-Ling Tang Key Laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200030China Department of Thoracic Surgery Southwest HospitalArmy Medical University(Third Military Medical University)Chongqing 400038China Department of Anesthesiology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646099China

To the Editor:Substrate rigidity and topography are two important biomechanical factors that can modulate the biological behavior of cancer cells such as epithelial to mesenchymal transition(EMT).Currently,although studies have begun to focus on how the mechanical microenvironment determines the fate of multiple cells,the mechanism of the mechanical microenvironment affecting EMT is still unclear.

关键词： transition rigidity mesenchymal

Epithelial defect repair in the auricle and auditory meatus by grafting with cultured adipose-derived mesenchymal stem cell aggregate-extracellular matrix

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Chinese Medical Journal 2019年第6期132卷 680-689页

作者： Wen-Jin Zhang Lei-Guo Ming Jian-Jun Sun Center of Otolaryngology Head and Neck Surgery Chinese PLA Navy General Hospital Beijing 100048 China School of Postgraduate Anhui Medical University Hefei Anhui 230032 China State Key Laboratory of Military Stomatology Center for Tissue Engineering School of Stomatology Fourth Military Medical University Xi'an Shaanxi 710032 China Research and Development Center for Tissue Engineering Fourth Military Medical University Xi'an Shaanxi 710032 China

Background: Several patients experience persistent otorrhea after a flawless surgical procedure because of insufficient epithelial healing. Several efforts, such as autologous tissue allograft and xenograft, have been made to halt otorrhea. However, a stable technology to induce temporal epithelial repair is yet to be established. Therefore, this study aims to investigate whether implantation of seeding adipose-derived mesenchymal stem cell (ADMSC) aggregates on extracellular matrix (ECM;herein, ADMSC aggregate-ECM) into damaged skin wound promotes skin regeneration. Methods: ADMSC aggregate-ECM was prepared using a previously described procedure that isolated ADMSCs from rabbits and applied to the auricle and auditory meatus wound beds of New Zealand white rabbits. Wound healing was assessed by general observation and hematoxylin and eosin (H&E) staining. Secretion of growth factor of the tissue was evaluated by western blotting. Two other groups, namely, ECM and control, were used. Comparisons of three groups were conducted by one-way analysis of variance analysis. Results: ADMSCs adhered tightly to the ECM and quickly formed cell sheets. At 2 weeks, general observation and H&E staining indicated that the wound healing rates in the ADMSC aggregate-ECM (69.02±6.36%) and ECM (59.32 + 4.10%) groups were higher than that in the control group (43.74± 12.15%;P=0.005, P<0.001, respectively) in ear auricle excisional wounds. At 7 weeks, The scar elevation index was evidently reduced in the ADMSC aggregate-ECM (2.08±0.87) and ECM (2.31 ±0.33) groups compared with the control group (4.06 ±0.45;P < 0.001, P < 0.001, respectively). In addition, the scar elevation index of the ADMSC aggregate-ECM group reached the lowest rate 4 weeks in advance. In auditory meatus excisional wounds, the ADMSC aggregate-ECM group had the largest range of normal skin-like structure at 4 weeks. The ADMSC aggregate-ECM and ECM groups secreted increased amounts of growth factors that contributed to skin regeneration at weeks 1 and 2, respectivel

关键词： Adipose-derived mesenchymal stem cell Extracellular matrix Otorrhea Rabbit Skin regeneration Wound healing