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Comparative analysis of biological characteristics of adult mesenchymal stem cells with different tissue origins

Asian Pacific Journal of Tropical Medicine 2015年第9期8卷 725-731页

作者： Jin-Yang Chen Xiao-Zhou Mou Xiao-Chun Du Charlie Xiang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital College of Medicine Zhejiang University Clinical Research Institute Zhejiang Provincial People's Hospital S-Evans Biosciences

Objective: To invest the dif erences among mesenchymal stem cells(MSCs) derived from different tissues and their impacts on clinical applications. Methods: In this study, MSCs were isolated from adipose tissue(AD), umbilical cord tissue(UC), and menstrual blood(Men) and comparedtheir biological characteristics in terms of proliferation capacity, passage capacity, colony formation, and surface markers were compared. Results: The stem cells(SCs) obtained from different sources were all characterized as MSCs, but demonstrated some dif erences. Umbilical cord-derived MSCs(UCMSCs) were able to overcome density inhibition. The proliferation rate decreased in the order UCMSCs> Men SCs> ADSCs, while the colony-forming ability decreased in the order Men SCs> ADSCs> UCMSCs. Based on gene-expression data for MSCs from dif erent sources within the same donor, 768 Men SC genes were found that were specii cally upregulated or downregulated compared with bone marrow-derived MSCs and UCMSCs, most of which were involved in cell function-related pathways. In addition, Men SCs appeared to be superior in terms of immune inl ammation, stress response, and neural dif erentiation potentials, but weaker in terms of osteogenic and chondrogenic dif erentiation capacities, compared with UCMSCs and bone marrow-derived MSCs. Conclusions: Men SCs have higher extraction ei ciency, colony-forming ability, and long time passage capacity. Although the proliferation capacity is inferior to UCMSCs.

关键词： Adipose Umbilical cord Menstrual blood mesenchymal stem cell

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Use of mesenchymal stem cells to treat liver fibrosis:Current situation and future prospects

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World Journal of Gastroenterology 2015年第3期21卷 742-758页

作者： Silvia Berardis Prenali Dwisthi Sattwika Mustapha Najimi Etienne Marc Sokal Laboratory of Pediatric Hepatology and Cell Therapy Institut de Recherche Expérimentale et CliniqueCliniques Universitaires St LucUniversité Catholique de Louvain1200 BrusselsBelgium

Progressive liver fibrosis is a major health issue for which no effective treatment is available,leading to cirrhosis and orthotopic liver transplantation.However,organ shortage is a reality.Hence,there is an urgent need to find alternative therapeutic strategies.Cellbased therapy using mesenchymal stem cells(MSCs) may represent an attractive therapeutic option,based ontheir immunomodulatory properties,their potential to differentiate into hepatocytes,allowing the replacement of damaged hepatocytes,their potential to promote residual hepatocytes regeneration and their capacity to inhibit hepatic stellate cell activation or induce their apoptosis,particularly via paracrine mechanisms.The current review will highlight recent findings regarding the input of MSC-based therapy for the treatment of liver fibrosis,from in vitro studies to pre-clinical and clinical trials.Several studies have shown the ability of MSCs to reduce liver fibrosis and improve liver function.However,despite these promising results,some limitations need to be considered.Future prospects will also be discussed in this review.

关键词： Liver fibrosis Cirrhosis mesenchymal stem cells Ce

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Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature

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World Journal of Gastroenterology 2015年第20期21卷 6409-6416页

作者： Jiang Li Jin-Zhen Cai Qing-Jun Guo Jun-Jie Li Xiao-Ye Sun Zhan-Dong Hu David KC Cooper Zhong-Yang Shen Department of Transplant Surgery Tianjin First Central Hospital Department of Pathology Tianjin First Central Hospital Thomas E Starzl Transplantation Institute University of Pittsburgh

mesenchymal hamartomas of the liver(MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography(CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen includedintraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg(dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months after transplantation, the patient remains well and is ful

关键词： Liver mesenchymal hamartoma Adult Organ donor After cardiac death Transplantation

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Multipotent mesenchymal stromal cells:A promisingstrategy to manage alcoholic liver disease

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World Journal of Gastroenterology 2016年第1期22卷 24-36页

作者： Fernando Ezquer Flavia Bruna Sebastián Calligaris Paulette Conget Marcelo Ezquer Centro de Medicina Regenerativa Facultad de MedicinaClínica Alemana-Universidad del DesarrolloSantiago 7710162Chile

Chronic alcohol consumption is a major cause of liver disease.The term alcoholic liver disease(ALD)refers to a spectrum of mild to severe disorders including steatosis,steatohepatitis,cirrhosis,and hepatocellular carcinoma.With limited therapeutic options,stem cell therapy offers significant potential for these patients.In this article,we review the pathophysiologic features of ALD and the therapeutic mechanisms of multipotent mesenchymal stromal cells,also referred to as mesenchymal stem cells(MSCs),based on their potential to differentiate into hepatocytes,their immunomodulatory properties,their potential to promote residual hepatocyte regeneration,and their capacity to inhibit hepatic stellate cells.The perfect match between ALD pathogenesis and MSC therapeutic mechanisms,together with encouraging,available preclinical data,allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage ALD onset and progression.

关键词： Alcoholic liver disease Cellular therapy Alcoholic steatohepatitis Hepatic function recovery mesenchymal stem cells

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Gingival-derived mesenchymal stem cells:An endless resource for regenerative dentistry

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World Journal of Stem Cells 2018年第9期10卷 116-118页

作者： Mohammed E Grawish Department of Oral Biology Faculty of DentistryMansoura University

The gingiva, the masticatory portion of the oral mucosa, is excised and discarded frequently during routine dental treatments and following tooth extraction, dental crown lengthening, gingivectomy and periodontal surgeries. Subsequent to excision, healing eventually happens in a short time period after gingival surgery. Clinically, the gingival tissue can be collected very easily and, in the laboratory, it is also very easy to isolate gingival-derived mesenchymal stem cells (GMSCs) from this discarded gingival tissue. GMSCs, a stem cell population within the lamina propria of the gingival tissue, can be isolated from attached and free gingiva, inflamed gingival tissu-es, and from hyperplastic gingiva. Comparatively, they constitute more attractive alternatives to other dental-derived mesenchymal stem cells due to the availability and accessibility of gingival tissues. They have unique immunomodulatory functions and well-documented self-renewal and multipotent differentiation properties. They display positive signals for Stro-1, Oct-4 and SSEA-4 pluripotency-associated markers, with some co-expre-ssing Oct4/Stro-1 or Oct-4/SSEA-4. They should be considered as the best stem cell source for cell-based therapies and regenerative dentistry. The clinical use of GMSCs for regenerative dentistry represents an attrac-tive therapeutic modality. However, numerous biological and technical challenges need to be addressed prior to considering transplantation approaches of GMSCs as clinically realistic therapies for humans.

关键词： Gingival-derived mesenchymal stem cells Regenerative dentistry Lamina propria of the gingiva Gingiva Stem cell therapy

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Challenges in animal modelling of mesenchymal stromal cell therapy for inflammatory bowel disease

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World Journal of Gastroenterology 2015年第16期21卷 4779-4787页

作者： Raghavan Chinnadurai Spencer Ng Vijayakumar Velu Jacques Galipeau Department of Hematology and Oncology Winship Cancer InstituteEmory University Emory Vaccine Center Yerkes National Primate Research CenterEmory University Department of Pediatrics Emory University

Utilization of mesenchymal stromal cells(MSCs) for the treatment of Crohn's disease and ulcerative colitis is of translational interest.Safety of MSC therapy has been well demonstrated in early phase clinical trials but efficacy in randomized clinical trials needs to be demonstrated.Understanding MSC mechanisms of action to reduce gut injury and inflammation is necessary to improve current ongoing and future clinical trials.However, two major hurdles impede the direct translation of data derived from animal experiments to the clinical situation:(1) limitations of the currently available animal models of colitis that reflect human inflammatory bowel diseases(IBD).The etiology and progression of human IBD are multifactorial and hence a challenge to mimic in animal models; and(2) Species specific differences in the functionality of MSCs derived from mice versus humans.MSCs derived from mice and humans are not identical in their mechanisms of action in suppressing inflammation.Thus, preclinical animal studies with murine derived MSCs cannot be considered as an exact replica of human MSC based clinical trials.In the present review, we discuss the therapeutic properties of MSCs in preclinical and clinical studies of IBD.We also discuss the challenges and approaches of using appropriate animal models of colitis, not only to study putative MSC therapeutic efficacy and their mechanisms of action, but also the suitability of translating findings derived from such studies to the clinic.

关键词： mesenchymal stromal cells Inflammatorybowel disease colitis Animal model Crohn's disaese

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Effect of h GC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice

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Asian Pacific Journal of Tropical Medicine 2016年第8期9卷 774-778页

作者： Lin Song Xin Zhou Hong-Jun Jia Mei Du Jin-Ling Zhang Liang Li Oncology Department No.2 Linyi People's Hospital of Shandong Province Radiotherapy Technology Department Linyi People's Hospital of Shandong Province

Objective: To study the effect of h GC-MSCs from human gastric cancer tissue on cell proliferation, invasion and epithelial-mesenchymal transition in tumor tissue of gastric cancer tumor-bearing mice. Methods: BABL/c nude mice were selected as experimental animals and gastric cancer tumor-bearing mice model were established by subcutaneous injection of gastric cancer cells, randomly divided into different intervention groups. h GC-MSCs group was given different amounts of gastric cancer cells for subcutaneous injection, PBS group was given equal volume of PBS for subcutaneous injection. Then tumor tissue volume were determined, tumor-bearing mice were killed and tumor tissues were collected, m RNA expression of proliferation, invasion, EMT related molecules were determined. Results: 4, 8, 12, 16, 20 d after intervention, tumor tissue volume of h GC-MSCs group were significantly higher than those of PBS group and the more the number of h GC-MSCs, the higher the tumor tissue volume; m RNA contents of Ki-67, PCNA, Bcl-2, MMP-2, MMP-7, MMP-9, MMP-14, N-cadherin, vimentin, Snail and Twist in tumor tissue of h GC-MSCs group were higher than those of PBS group, and m RNA contents of Bax, TIMP1, TIMP2 and E-cadherin were lower than those of PBS group. Conclusions: h GC-MSCs from human gastric cancer tissue can promote the tumor growth in gastric cancer tumor-bearing mice, and the molecular mechanism includes promoting cell proliferation, invasion and epithelial-mesenchymal transition.

关键词： Gastric cancer mesenchymal stem cells Proliferation Invasion Epithelial-mesenchymal transition

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Effect of bone marrow mesenchymal stem cells on the Smad expression of hepatic fibrosis rats

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Asian Pacific Journal of Tropical Medicine 2014年第4期7卷 321-324页

作者： Zhen-Chang Wang Shan Yang Jing-Jing Huang Song-Lin Chen Quan-Qiang Li Yuan Li Liver Disease Center First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine Guangxi University of Traditional Chinese Medicine

Objective:To investigate the impact of bone marrow mesenchymal stem cells on Smad expression of hepatic fibrosis rats.Methods:A total of 48 adult female SD rats were randomly divided into three groups,normal control group(n=10),observation group(n=19)with liver fibrosis model rats injected with BMSCs cells:model group(n=19),with liver fibrosis model rats injected with physiological saline.Serum index,TGF-β1 and Smad expression were detected.Results:TypeⅢprocollagen,Ⅳcollagen,hyaluronic acid,laminin levels of observation group were significantly lower than those of model group(P<0.05).The content and expression of TGF-β1in serum and liver tissue of observation group were significantly lower than those of model group(P<0.05).Compared with normal control group,the Smad3,Smad4 mRNA and protein expression of model group were significantly increased,the Smad7 mRNA and protein expression were significantly reduced(P<0.05).Compared with model group.Smad3,Smad4 mRNA and protein expression of observation group were significantly reduced,and Smad7 mRNA expression were significantly increased(P<0.05).Conclusions:BMSCs can regulate Smad expression to some extent,and reduce the degree of liver fibrosis.

关键词： Bone mesenchymal stem cells Hepatic fibrosis rats Smadv

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An experimental study of preventing and treating acute radioactive enteritis with human umbilical cord mesenchymal stem cells

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Asian Pacific Journal of Tropical Medicine 2013年第12期6卷 968-971页

作者： Rui Wang Wei Yuan Qiang Zhao Peng Song Ji Yue Shi-De Lin Ting-Bao Zhao Jinan Miltary General Hospital People's Hospital of Zhangqiu

Objective:To test the curative effect of human umbilical cord-derived mesenchymal stem cells on rat acute radioactive enteritis and thus in provide clinical therapeutic basis for radiation sickness.Methods:Human umbilical cord-derived mesenchymal stem cells were cultivated in vitro and the model of acute radioactive enteritis of rats was established.Then,the umbilical cord mesenchymal stem cells were injected into the rats via tail vein.Visual and histopathiological changes of the experimental rats were observed.Results:After the injection,the rats in the prevention group and treatment group had remarkably better survival status than those in the control group.The histological observations revealed that the former also had better intestinal mucosa structure,more regenerative cells and stronger proliferation activity than the latter.Conclusions:Human umbilical cord-derived mesenchymal stem cells have a definite therapeutic effect on acute radioactive enteritis in rats.

关键词： Radioactive contamination Human umbilical cord mesenchymal stem cells Acute radioactive enteritis Rat

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Experimental treatment of radiation pneumonitis with human umbilical cord mesenchymal stem cells

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Asian Pacific Journal of Tropical Medicine 2014年第4期7卷 262-266页

作者： Rui Wang Chang-zheng Zhu Ping Qiao Jian Liu Qiang Zhao Kui-jie Wang Ting-bao Zhao Department of Spinal Cord Repairing Jinan Miliary General Hospital Department of Neurology People's Hospital of Zhangqiu Department of Orthopedics People's Hospital of Zhangqiu

Objective:To evaluate of the curative effect of human umbilical cord mesenchymal stem cells(hUC-MSCs)on rat acute radiation pneumonitis.Methods:Fourty rats were randomly divided into control group,radiation group,stem cell prevention group,stem cell treatment group and prednisone treatment group.All rats except those in the control group were radiated with X ray to establish the acute radiation pneumonitis damage model.The hUC-MSCs cultured in vitro was administrated to the rats of the prevention group via tail vein(1×10~6 cells/kg BW)24 h before the radiation,while the same administration was performed in the rats of the treatment group 24 h after the radiation.After 24 h post the radiation,the rats in tbe radiation group were given 0.4 mL physiological saline,and those in the prednisone group were given 1 mg/kg prednisone.All rats were,observed and executed 72 h after the radiation to defect lung histological changes.Results:After the administration of hUC-MSCs,the survival status of the rats in the prevention group and treatment group was obviously better than that in the control group.As shown by the histological staining,the morphology,proliferation activity aad bronchial state of lung tissues were better in the prevention group and treatment group than in the control group.Conclusion:The hUC-MSCs have definite therapeutic effects on acute radiation pneumonitis in rats.

关键词： Human umbilical cord mesenchymal stem cell Radiation pneumonitis Rat

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