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Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2012年第8期13卷 616-623页

作者： Xian-bao LIU Han CHEN Hui-qiang CHEN Mei-fei ZHU Xin-yang HU Ya-ping WANG Zhi JIANG Yin-chuan XU Mei-xiang XIANG Jian-an WANG Cardiovascular Key Lab of Zhejiang Province the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Cardiology the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Intensive Care Unit Zhejiang Provincial Hospital of Traditional Chinese MedicineHangzhou 310006China

Objective:Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and sub-sequent heart function improvement after transplantation. Methods: MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5- Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl trans-ferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson's trichrome staining, respectively. Results: Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group. Conclusions:Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.

关键词：间充质的干细胞 Angiopoietin-1 Preconditioning 幸存心肌的梗塞

Mesenchymal stromal cell-based therapy: Regulatory and translational aspects in gastroenterology

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World Journal of Gastroenterology 2016年第41期22卷 9057-9068页

作者： Giovanni Dothel Emanuel Raschi Roberto Rimondini Fabrizio De Ponti Pharmacology Unit Department of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna

The past decade has witnessed an outstanding scientific production focused towards the possible clinical applications of mesenchymal stromal cells(MSCs) in autoimmune and chronic inflammatory diseases. This raised the need of novel standards to adequately address quality, efficacy and safety issues of this advanced therapy. The development of a streamlined regulation is currently hampered by the complexity of analyzing dynamic biological entities rather than chemicals. Although numerous pieces of evidence show efficacy in reducing intestinal inflammation, some inconsistencies between the mechanisms of action of rodent vs human MSCs suggest caution before assigning translational value to preclinical studies. Preliminary evidence from clinical trials showed efficacy of MSCs in the treatment of fistulizing Crohn's disease(CD), and preparations of heterologous MSCs for CD treatment are currently tested in ongoing clinical trials. However, safety issues, especially in longterm treatment, still require solid clinical data. In this regard, standardized guidelines for appropriate dosing and methods of infusion could enhance the likelihood to predict more accurately the number of responders and the duration of remission periods. In addition, elucidating MSC mechanisms of action could lead to novel and more reliable formulations such as those derived from the MSCs themselves(e.g., supernatants).

关键词：间充质的 stromal 房间间充质的干细胞煽动性的肠疾病肠的混乱翻译的药

Mesenchymal stem cells rescue acute hepatic failure by polarizing M2 macrophages

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World Journal of Gastroenterology 2017年第45期23卷 7978-7988页

作者： yan-wei li chong zhang qiu-ju sheng han bai yang ding xiao-guang dou department of infectious diseases shengjing hospital of china medical university

AIM To investigate whether M1 or M2 polarization contributes to the therapeutic effects of mesenchymal stem cells(MSCs) in acute hepatic failure(AHF).METHODS MSCs were transfused into rats with AHF induced by D-galactosamine(DGal N). The therapeutic effects of MSCs were evaluated based on survival rate and hepatocyte proliferation and apoptosis. Hepatocyte regeneration capacity was evaluated by the expression of the hepatic progenitor surface marker epithelial cell adhesion molecule(Ep CAM). Macrophage polarization was analyzed by M1 markers [CD68,tumor necrosis factor alpha(TNF-α),interferon-γ(IFN-γ),inducible nitric oxide synthase(INOS)] and M2 markers [CD163,interleukin(IL)-4,IL-10,arginase-1(Arg-1)] in the survival and death groups after MSC transplantation.RESULTS The survival rate in the MSC-treated group was increased compared with the DPBS-treated control group(37.5% vs 10%). MSC treatment protected rats with AHF by reducing apoptotic hepatocytes and promoting hepatocyte regeneration. Immunohistochemical analysis showed that MSC treatment significantly increased the expression of Ep CAM compared with the control groups(P < 0.001). Expression of Ep CAM in the survival group was significantly up-regulated compared with the death group after MSC transplantation(P = 0.003). Transplantation of MSCs significantly improved the expression of CD163 and increased the gene expression of IL-10 and Arg-1 in the survival group. IL-4 concentrations were significantly increased compared to the death group after MSC transplantation(88.51 ± 24.51 pg/m L vs 34.61 ± 6.6 pg/m L,P < 0.001). In contrast,macrophages showed strong expression of CD68,TNF-α,and INOS in the death group. The concentration of IFN-γ was significantly increased compared to the survival group after MSC transplantation(542.11 ± 51.59 pg/m L vs 104.07 ± 42.80 pg/m L,P < 0.001).CONCLUSION M2 polarization contributes to the therapeutic effects of MSCs in AHF by altering levels of anti-inflammatory and pro-inflammatory factors.

关键词：尖锐肝的失败间充质的干细胞巨噬细胞极化发炎

Stem cell therapy for nerve injury

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World Journal of Stem Cells 2017年第9期9卷 144-151页

作者： Sara Sayad Fathi Arash Zaminy Department of Anatomical Sciences School of MedicineGuilan University of Medical Sciences Neuroscience Research Center School of MedicineGuilan University of Medical Sciences

Peripheral nerve injury has remained a substantial clinical complication with no satisfactory treatment options.Despite the great development in the field ofmicrosurgery,some severe types of neural injuries cannot be treated without causing tension to the injured nerve.Thus current studies have focused on the new approaches for the treatment of peripheral nerve injuries.Stem cells with the ability to differentiate into a variety of cell types have brought a new perspective to this matter.In this review,we will discuss the use of three main sources of mesenchymal stem cells in the treatment of peripheral nerve injuries.

关键词：基于房间的治疗外部神经损害干细胞间充质的干细胞骨头髓间充质的干细胞脂肪质导出间充质的干细胞脐的绳索间充质的干细胞

Regenerative medicine using dental pulp stem cells for liver diseases

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2017年第1期8卷 1-6页

作者： Shogo Ohkoshi Hajime Hara Haruka Hirono Kazuhiko Watanabe Katsuhiko Hasegawa Department of Internal Medicine School of Life Dentistry at NiigataNippon Dental UniversityChuo-ku 951-8580Japan

Acute liver failure is a refractory disease and its pro-gnosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells(MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti--inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review.

关键词：牙齿的肉间充质的干细胞再生药肝疾病牙齿银行