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Comparison between the therapeutic effects of differentiated and undifferentiated wharton’s jelly mesenchymal stem cells in rats with streptozotocin-induced diabetes

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World Journal of stem cells 2020年第2期12卷 139-151页

作者： Chen-Yuan Hsiao Tien-Hua Chen Ben-shian Huang Po-Han Chen Cheng-Hsi su Jia-Fwu shyu Pei-Jiun Tsai Graduate Institute of Medical sciences National Defense Medical CenterTaipei 114Taiwan Department of surgery Landseed International HospitalTaoyuan 324Taiwan Institute of Anatomy and cell Biology School of MedicineNational Yang Ming UniversityTaipei 112Taiwan Trauma Center Department of SurgeryVeterans General HospitalTaipei 112Taiwan Division of General surgery Department of SurgeryVeterans General HospitalTaipei 112Taiwan Department of Obstetrics and Gynecology Veterans General HospitalTaipei 112Taiwan Department of surgery Cheng Hsin General HospitalTaipei 112Taiwan Department of Biology and Anatomy National Defense Medical CenterTaipei 114Taiwan Department of Critical Care Medicine Veterans General HospitalTaipei 112Taiwan

BACKGROUND Despite the availability of current therapies,including oral antidiabetic drugs and insulin,for controlling the symptoms caused by high blood glucose,it is difficult to cure diabetes mellitus,especially type 1 diabetes *** cell therapies using mesenchymal stem cells(MsCs)may be a promising ***,the therapeutic mechanisms by which MsCs exert their effects,such as whether they can differentiate into insulin-producing cells (IPCs) beforetransplantation, are *** this study, we used three types of differentiation media over 10 d to generateIPCs from human wharton’s jelly MsCs (hWJ-MsCs). We further transplantedthe undifferentiated hWJ-MsCs and differentiated IPCs derived from them intothe portal vein of rats with streptozotocin-induced diabetes, and recorded thephysiological and pathological *** fluorescent staining and C-peptide enzyme-linked immunoassay, we wereable to successfully induce the differentiation of hWJ-MsCs into *** of both IPCs derived from hWJ-MsCs and undifferentiated hWJMsCshad the therapeutic effect of ameliorating blood glucose levels andimproving intraperitoneal glucose tolerance tests. The transplanted IPCs homedto the pancreas and functionally survived for at least 8 wk after transplantation,whereas the undifferentiated hWJ-MsCs were able to improve the insulitis andameliorate the serum inflammatory cytokine in streptozotocin-induced *** IPCs can significantly improve blood glucose levels in diabetic ratsdue to the continuous secretion of insulin by transplanted cells that survive in theislets of diabetic rats. Transplantation of undifferentiated hWJ-MsCs cansignificantly improve insulitis and re-balance the inflammatory condition indiabetic rats with only a slight improvement in blood glucose levels.

关键词： human wharton’s jelly mesenchymal stem cell Insulin-producing cells Diabetes mellitus Differentiation Regeneration therapy Anti-inflammatory

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