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Potential advantages of acute kidney injury management by mesenchymal stem cells

World Journal of Stem Cells 2014年第5期6卷 644-650页

作者： Francesca Bianchi Elisa Sala Chiara Donadei Irene Capelli Gaetano La Manna Laboratory of Molecular Biology and Stem Cell Engineering-National Institute of Biostructures and Biosystems Department of Experimental Diagnostic and Specialty Medicine S. Orsola-Malpighi Hospital University of Bologna40138 Bologna Italy Department of Experimental Diagnostic and Specialty Medicine (DIMES) Nephrology Dialysis and Renal Transplant UnitSt Orsola Hospital University of Bologna 40128 BolognaItaly

Mesenchymal stem cells are currently considered as a promising tool for therapeutic application in acute kidney injury(AKI) management. AKI is characterized by acute tubular injury with rapid loss of renal function. After AKI, inflammation, oxidative stress and excessive deposition of extracellular matrix are the molecular events that ultimately cause the end-stage renal disease. Despite numerous improvement of supportive therapy, the mortality and morbidity among patients remain high. Therefore, exploring novel therapeutic options to treat AKI is mandatory. Numerous evidence in animal models has demonstrated the capability of mesenchymal stem cells(MSCs) to restore kidney function after induced kidney injury. After infusion, MSCs engraft in the injured tissue and release soluble factors and microvesicles that promote cell survival and tissue repairing. Indeed, the main mechanism of action of MSCs in tissue regeneration is the paracrine/endocrine secretion of bioactive molecules. MSCs can be isolated from several tissues, including bone marrow, adipose tissue, and blood cord; pre-treatment procedures to improve MSCs homing and their paracrine function have been also described. This review will focus on the application of cell therapy in AKI and it will summarize preclinical studies in animal models and clinical trials currently ongoing about the use of mesenchymal stem cells after AKI.

关键词： Mesenchymal stem cells Paracrine Soluble factors Microvesicle Acute kidney injury Regenerative medicine preclinical Clinical trial

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CXCL12 Retargeting of an Oncolytic Adenovirus Vector to the Chemokine CXCR4 and CXCR7 Receptors in Breast Cancer

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Journal of Cancer Therapy 2021年第6期12卷 311-336页

作者： Samia M. O’Bryan J. Michael Mathis Department of Comparative Biomedical Sciences School of Veterinary Medicine Louisiana State University Baton Rouge LA USA University of North Texas Health Science Center Graduate School of Biomedical Sciences Fort Worth TX USA

Breast cancer is the most frequently diagnosed cancer in women under 60, and the second most diagnosed cancer in women over 60. While significant progress has been made in developing targeted therapies for breast cancer, advanced breast cancer continues to have high mortality, with poor 5-year survival rates. Thus, current therapies are insufficient in treating advanced stages of breast cancer;new treatments are sorely needed to address the complexity of advanced-stage breast cancer. Oncolytic virotherapy has been explored as a therapeutic approach capable of systemic administration, targeting cancer cells, and sparing normal tissue. In particular, oncolytic adenoviruses have been exploited as viral vectors due to their ease of manipulation, production, and demonstrated clinical safety profile. In this study, we engineered an oncolytic adenovirus to target the chemokine receptors CXCR4 and CXCR7. The overexpression of CXCR4 and CXCR7 is implicated in the initiation, survival, progress, and metastasis of breast cancer. Both receptors bind to the ligand, CXCL12 (SDF-1), which has been identified to play a crucial role in the metastasis of breast cancer cells. This study incorporated a T4 fibritin protein fused to CXCL12 into the tail domain of an adenovirus fiber to retarget the vector to the CXCR4 and CXCR7 chemokine receptors. We showed that the modified virus targets and infects CXCR4- and CXCR7-overexpressing breast cancer cells more efficiently than a wild-type control vector. In addition, the substitution of the wild-type fiber and knob with the modified chimeric fiber did not interfere with oncolytic capability. Overall, the result

关键词： Adenovirus Breast Cancer Cancer Chemokine CXCL12 CXCR4 CXCR7 Oncolytic preclinical Receptor Virotherapy Virus

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Advantages and limitations in the establishment and utilization of patient-derived xenografts in gastric cancer

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Oncology and Translational Medicine 2017年第1期3卷 3-9页

作者： Zuhua Chen Lin Shen Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer Hospital&InstituteBeijing 100142China

Owing to the high genetic heterogeneity of tumors, small number of therapeutic strategies available, and frequent presentation of drug resistance, the prognosis for patients with advanced gastric cancer(AGC) are unsatisfactory. The utility of traditional cancer cell lines in translational research is limited by their poor correspondence to the genomic alterations and expression profiles that occur in actual patient tumors. In the last decade, increasing attention has been given to patient-derived tumor xenografts(PDTXs), which can faithfully recapitulate the histopathology, molecular characteristics, and therapeutic responses of the patient's tumor. However, the widespread development and utilization of PDTXs is restricted by factors such as the timeframe of establishment, lymphoma transformation during passaging, the immunodeficient microenvironment, and pharmacokinetic differences between mice and humans. In this review, we summarize the establishment and characterization of PDTX models for gastric cancer(GC). We then weigh the advantages and limitations of PDTXs when used to evaluate novel compounds, identify effective biomarkers, demonstrate resistance mechanisms, and predict clinical outcomes.

关键词： patient-derived tumor xenograft (PDTX) gastric cancer (GC) preclinical research

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Lab-to-clinic application of stem cell therapy for stroke

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Chinese Neurosurgical Journal 2016年第4期2卷 219-222页

作者： Mia C.Borlongan Sonya Kong David C.Hess Center of Excellence for Aging and Brain Repair Morsani College of Medicine University of South Florida 12901 Bruce B.Downs Blvd. Tampa FL 33612 USAResearch Service at James Haley VA Hospital Tampa FL 33612USA Department of Neurology Medical College of Georgia Augusta University 1120 15th Street Augusta GA 30912 USA

Stem cell therapy or 'cell therapy' has been demonstrated to be a potent treatment intervention in animal models of acute ischemic stroke,and recently has been introduced as an experimental therapy in early phase clinical *** the many stem cells,the bone marrow adherent cell type known as mesenchymal stem ceils have emerged in laboratory studies as a safe and effective therapy for ischemic stroke and other brain *** particular,a unique population of adherent bone marrow-derived cells,called MultiStem cells,display immunomodulatory effects and are a promising allogeneic cell therapy in acute ischemic ***,we describe the preclinical evidence supporting the use of MultiStem in the acute setting of ischemic stroke and the translation into an early phase clinical trial in ischemic stroke.

关键词： Multistem Cerebral ischemia preclinical Clinical Translational

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