title: Infusion with Human Bone Marrow-derived Mesenchymal Stem Cells Improves β-cell Function in Patients and Non-obese Mice with Severe Diabetes.
abstract: Mesenchymal stem cells (MSCs) transplantation is a promising therapeutic strategy for type 1 diabetes (T1D). However, little is known on whether MSC transplantation can benefit T1D patients with ketoacidosis and its potential actions. Here, we show that infusion with bone marrow MSCs preserves β-cell function in some T1D patients with ketoacidosis by decreasing exogenous insulin requirement and increasing plasma C-peptide levels up to 1-2 years. MSC transplantation increased plasma and islet insulin contents in non-obese diabetic (NOD) mice with severe diabetes. In comparison with severe diabetes controls, MSC infusion reduced insulitis, decreased pancreatic TNF-α, and increased IL-10 and TGF-β1 expression in NOD mice. MSC infusion increased the percentages of splenic Tregs and levels of plasma IL-4, IL-10 and TGF-β1, but reduced the percentages of splenic CD8+T and levels of plasma IFN-γ, TNF-α and IL-17A in NOD mice. Finally, infused MSCs predominantly accumulated in pancreatic tissues at 28 days post infusion. The effects of MSCs on preserving β-cell function and modulating inflammation tended to be dose-dependent and multiple doses of MSCs held longer effects in NOD mice. Hence, MSC transplantation preserved β-cell function in T1D patients and NOD mice with severe diabetes by enhancing Treg responses.
authors.affiliation: Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.|School of Clinical Medicine and Nursing, Suzhou Vocational Health College, Jiangsu, China.
authors.forename: Lirong
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hui
authors.affiliation: Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.
authors.forename: Qianyue
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, No. 321, Zhongshan Road, Nanjing, 210008, China.
authors.forename: Dalong
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D001854:Bone Marrow Cells / Q000166:cytology*; D002096:C-Peptide / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007249:Inflammation; D050417:Insulin-Secreting Cells / Q000166:cytology*; D016753:Interleukin-10 / Q000378:metabolism; D007662:Ketosis; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D002096:C-Peptide; D016207:Cytokines; C556062:IL10 protein, mouse; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10