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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

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

Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders

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World Journal of Stem Cells 2019年第2期11卷 55-72页

作者： Qiang Liu Mo-Xian Chen Lin Sun Chloe U Wallis Jian-Song Zhou Li-Juan Ao Qi Li Pak C Sham Department of Surgery The Chinese University of Hong Kong School of Rehabilitation Kunming Medical University Department of Psychology Weifang Medical University Medical Sciences Division University of Oxford Mental Health Institute of the Second Xiangya Hospital Central South University Department of Psychiatry the University of Hong Kong State Key Laboratory of Brain and Cognitive Sciences Center for Genomic Sciences the University of Hong Kong

Autism and autism spectrum disorders(ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. mesenchymal stem cells(MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for ASD.Thus the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review willfocus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.

关键词： Autism spectrum disorders mesenchymal stem cells Major histocompatibility complex Inflammation Maternal immune activation Cell therapy

mesenchymal stem cell therapy in retinal and optic nerve diseases: An update of clinical trials

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World Journal of Stem Cells 2016年第11期8卷 376-383页

作者： Sonia Labrador-Velandia María Luz Alonso-Alonso Sara Alvarez-Sanchez Jorge González-Zamora Irene Carretero-Barrio José Carlos Pastor Iván Fernandez-Bueno Girish Kumar Srivastava Instituto Universitario de Oftalmobiología Aplicada Universidad de Valladolid 47011 Valladolid Spain Facultad de Medicina Universidad de Valladolid 47005 Valladolid Spain Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León 47011 Valladolid Spain Red Temática de Investigación Cooperativa Sanitaria del Instituto de Salud Carlos Ⅲ. Oftared 28029 Madrid Spain Hospital Clínico Universitario de Valladolid 47003 Valladolid Spain

Retinal and optic nerve diseases are degenerative ocular pathologies which lead to irreversible visual loss. Since the advanced therapies availability, cell-based therapies offer a new all-encompassing approach. Advances in the knowledge of neuroprotection, immunomodulation and regenerative properties of mesenchymal stem cells(MSCs) have been obtained by several preclinical studies of various neurodegenerative diseases. It has provided the opportunity to perform the translation of this knowledge to prospective treatment approaches for clinical practice. Since 2008, several first steps projecting new treatment approaches, have been taken regarding the use of cell therapy in patients with neurodegenerative pathologies of optic nerve and retina. Most of the clinical trials using MSCs are in Ⅰ/Ⅱ phase, recruiting patients or ongoing, and they have as main objective the safety assessment of MSCs using various routes of administration. However, it is important to recognize that, there is still a long way to go to reach clinical trials phase Ⅲ-Ⅳ. Hence, it is necessary to continue preclinical and clinical studies to improve this new therapeutic tool. This paper reviews the latest progress of MSCs in human clinical trials for retinal and optic nerve diseases.

关键词： mesenchymal stem cells Cell therapy Optic nerve diseases Clinical trials Retinal diseases

mesenchymal stem cells alleviate TNBS-induced colitis by modulating inflammatory and autoimmune responses

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World Journal of Gastroenterology 2013年第29期19卷 4702-4717页

作者： Qian-Qian Chen Li Yan Chang-Zheng Wang Wei-Hua Wang Hui Shi Bin-Bin Su Qing-Huan Zeng Hai-Tao Du Jun Wan Department of Gastroenterology Chinese PLA General Hospital Medical College of PLA Department of Gastroenterology Chinese PLA General Hospital

AIM: To investigate the potential therapeutic effects of mesenchymal stem cells (MSCs) in inflammatory bowel disease (IBD), we transplanted MSCs into an experimental model of IBD. METHODS: A rectal enema of trinitrobenzene sulfonic acid (TNBS) (100 mg/kg body weight) was administered to female BALB/c mice. Bone marrow mesenchymal stem cells (BMSCs) were derived from male green fluorescent protein (GFP) transgenic mice and were transplanted intravenously into the experimental animals after disease onset. Clinical activity scores and histological changes were evaluated. GFP and Sex determining region Y gene (SRY ) expression were used for cell tracking. Ki67 positive cells and Lgr5-expressing cells were determined to measure proliferative activity. Inflammatory response was determined by mea-suring the levels of different inflammatory mediators in the colon and serum. The inflammatory cytokines included tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-6, IL-17, IL-4, IL-10, and transforming growth factor (TGF-β). Master regulators of Th1 cells (T-box expressed in T cells, T-bet), Th17 cells (retinoid related orphan receptor gamma(t), RORγt), Th2 cells (GATA family of transcription factors 3, GATA3) and regulatory T cells (forkhead box P3, Foxp3) were also determined. RESULTS: Systemic infusion of GFP-BMSCs ameliorated the clinical and histopathologic severity of colitis, including body weight loss, diarrhea and inflammation, and increased survival (P < 0.05). The cell tracking study showed that MSCs homed to the injured colon. MSCs promoted proliferation of intestinal epithelial cells and differentiation of intestinal stem cells (P < 0.01). This therapeutic effect was mainly mediated by downregulation of both Th1-Th17-driven autoimmune and inflammatory responses (IL-2, TNF-α, IFN-γ, T-bet; IL-6, IL-17, RORγt), and by up-regulation of Th2 activities (IL-4, IL-10, GATA-3) (P < 0.05). MSCs also induced activated CD4 + CD25 + Foxp3 + regulatory T cells (TGF-β, IL-10, Foxp3) with a suppres

关键词： mesenchymal stem cells Transplantation Inflammatory bowel disease Inflammatory response Immunomodulation Trinitrobenzene sulfonic acid colitis Therapy

Pilose antler aqueous extract promotes the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells by stimulating the BMP-2/Smad1, 5/Runx2 signaling pathway

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Chinese Journal of Natural Medicines 2019年第10期17卷 756-767页

作者： REN Cong GONG Wei LI Feng XIE Ming School of Pharmacy L iaoning University of Traditional Chinese MedicineDalian 116600China Affiliated Hospital of Liaoning University of Traditional Chinese Medicine Shenyang 110032China

Peptides from Pilose antler aqueous extract(PAAE) have been shown to stimulate the proliferation and differentiation of bone marrow mesenchymal stem cells(BMSCs). However, the underlying molecular mechanisms are not well understood. Here, PAAE was isolated and purified to explore the molecular mechanisms underlying PAAE’s effects on BMSCs as well as its osteoprotective effects in ovariectomized rats. Our results showed that PAAE promoted proliferation and differentiation of BMSCs to become osteoblasts by enhancing ALP activity and increasing extracellular matrix mineralization. The trabecular microarchitecture of ovariectomized rats was also found to be protected by PAAE. Quantitative reverse transcription-polymerase chain reaction(Quantitative RT-PCR) results suggest that PAAE also increased the expression of osteogenic markers including, alkaline phosphatase(ALP), runt-related transcription factor 2(Runx2), osteocalcin(OCN), bone morphogenetic protein-2(BMP-2), and collagen I(COL-I). Immunoblotting results indicated that PAAE upregulated the levels of BMP-2 and Runx2 and was associated with Smad1/5 phosphorylation. PAAE A at the concentration of 200μg·mL^-1 showed the strongest effect on proliferation and osteogenic differentiation of BMSCs after 48 h. Using matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF MS), we identified the molecular weight of PAAE A and found that it is less than 3000 Da and showed several significant peaks. In conclusion, PAAE activates the BMP-2/Smad1, 5/Runx2 pathway to induce osteoblastic differentiation and mineralization in BMSCs and can inhibit OVX-induced bone loss. These mechanisms are likely responsible for its therapeutic effect on postmenopausal osteoporosis.

关键词： Pilose antler Postmenopausal osteoporosis Bone marrow mesenchymal stem cells BMP-2/Smad1,5/Runx2 signaling pathway

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

Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury

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Neural Regeneration Research 2019年第10期14卷 1780-1786页

作者： Feng Yan Ming Li Hong-Qi Zhang Gui-Lin Li Yang Hua Ying Shen Xun-Ming Ji Chuan-Jie Wu Hong An Ming Ren Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijingChina China-America Institute of Neuroscience Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Ultrasound Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Traditional Chinese Medicine Xuanwu HospitalCapital Medical UniversityBeijingChina Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijingChina

Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury.Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering.The scaffolds were impregnated with rat bone marrow mesenchymal stem cells.A traumatic brain injury rat model was established using the 300 g weight free fall impact method.Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain.Modified neurological severity scores were used to assess the recovery of neurological function.The Morris water maze was employed to determine spatial learning and memory abilities.Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue.Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine(BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein.Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores,shortened the average latency of the Morris water maze,increased the number of platform crossings,diminished the degeneration of damaged brain tissue,and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas.At 14 days after transplantation,increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area.The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone.To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds,immunosuppressive cyclosporine was intravenously inject

关键词： nerve regeneration stem cells collagen chitosan scaffolds traumatic brain injury bone marrow mesenchymal stem cells brain tissue engineering neural regeneration

Characterization and immunogenicity of bone marrow-derived mesenchymal stem cells under osteoporotic conditions

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Science China(Life Sciences) 2020年第3期63卷 429-442页

作者： Yingkang Huang Yin Yin Yanzheng Gu Qiaoli Gu Huilin Yang Zhengyu Zhou Qin Shi Orthopedic Department the First Affiliated Hospital of Soochow UniversityMedical College of Soochow UniversityOrthopedic Institute of Soochow UniversitySuzhou 215006China Laboratory Animal Center Medical College of Soochow UniversitySoochow UniversitySuzhou 215123China Clinical Immunology Institute of Jiangsu Province the First Affiliated Hospital of Soochow UniversitySuzhou 215006China Key Laboratory of Stem Cells and Biomedical Materials of Jiangsu Province and Chinese Ministry of Science and Technology Suzhou 215123China

mesenchymal stem cells(MSCs)are characterized by their multilineage potential and low immunogenicity.However,the properties of MSCs under pathological conditions are unclear.The current study investigated the differentiation potential and immunological characteristics of bone marrow-derived MSCs from ovariectomized-osteoporotic rats(OP-BMSCs).Although the expression of cell morphology-and stemness-related surface markers was similar between OP-BMSCs and BMSCs from healthy rats(H-BMSCs),the proliferation rate was significantly decreased compared with that of H-BMSCs.Regarding multilineage potential,osteogenesis and chondrogenesis abilities of OP-BMSCs decreased,but the adipogenesis ability was significantly enhanced compared with that of H-BMSCs.As expected,decreased osteogenesis following osteogenic induction resulted in reduced expression ofβ-catenin,osteocalcin,and runt-related transcription factor 2 in OP-BMSCs.Remarkably,the expression of the co-stimulatory proteins CD40 and CD80 was significantly higher,whereas the expression of the negative costimulatory molecule programmed cell death ligand 1 was significantly lower in the OP-BMSCs than that in H-BMSCs.Consequently,H-BMSCs inhibited the proliferation and secretion of inflammatory cytokines from anti-CD3 antibody-activated T cells,whereas OP-BMSCs did not.These results indicate that decreased osteogenesis and increased immunogenicity of OPBMSCs contribute to bone loss in osteoporosis.

关键词： mesenchymal stem cells osteogenesis chondrogenesis adipogenesis immunogenicity osteoporosis