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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2020, Vol. 40 Issue (7): 59-69    DOI: 10.13523/j.cb.2001061
综述     
干细胞改善糖尿病的分子机制及临床研究进展
陈飞,王晓冰,徐增辉(),钱其军()
上海细胞治疗工程技术研究中心 上海 201800
Molecular Mechanism and Clinical Research Progress of Mesenchymal Stem Cells in the Treatment of Diabetes Mellitus
CHEN Fei,WANG Xiao-bing,XU Zeng-hui(),QIAN Qi-jun()
Shanghai Cell Therapy Engineering Technology Research Center, Shanghai 200000, China
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摘要：

糖尿病是各种因素导致的高血糖慢性代谢疾病,已发展成为流行疾病之一。化学抗糖药虽能控制血糖水平,延缓病程进展,但需长期服用;胰岛移植能从根本上治愈糖尿病,但胰岛来源不足,且需终生应用免疫抑制剂,故并没有得到广泛应用;干细胞是一类能够自我复制的细胞,具有多向分化潜能和旁分泌特性,近年来的研究证明,干细胞在糖尿病治疗方面有着积极的效果,被认为是有效治疗糖尿病的理想细胞类型。因此,就干细胞治疗糖尿病的分子机制和临床研究现状进行简要阐述。
关键词： 糖尿病;  干细胞;  干细胞分化;  旁分泌    
Abstract:

Diabetes is a chronic metabolic disease of hyperglycemia caused by various factors, which has developed into one of the epidemic diseases. Chemical anti-diabetic drugs can control the blood glucose and delay the progress of the disease, which needs to be taken for a long time to be effectively controlled. The current gold standard therapy for pancreas transplantation, but it has not been widely used because of the shortage of pancreas and the need for long-term use of immunosuppressive drugs. Mesenchymal stem cells (MSCs) are a kind of self-proliferation cells with the potential of multi-directional differentiation and paracrine characteristics. Recent studies have proved that MSCs have positive effects in the treatment of diabetes, and are considered as the ideal cell type for treatment of diabetes. Therefore, this review The molecular mechanisms and clinical research of MSCs for diabetes mellitus were briefly described.
Key words: Diabetes mellitus    Mesenchymal stem cells    Mesenchymal stem cells differentiation    Paracrine
收稿日期: 2020-01-20 出版日期: 2020-08-13
ZTFLH:  Q813  
通讯作者: 徐增辉,钱其军     E-mail: zenghuixu@163.com;qianqj@163.com
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引用本文:

陈飞,王晓冰,徐增辉,钱其军. 干细胞改善糖尿病的分子机制及临床研究进展[J]. 中国生物工程杂志, 2020, 40(7): 59-69.

CHEN Fei,WANG Xiao-bing,XU Zeng-hui,QIAN Qi-jun. Molecular Mechanism and Clinical Research Progress of Mesenchymal Stem Cells in the Treatment of Diabetes Mellitus. China Biotechnology, 2020, 40(7): 59-69.

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https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2001061    或    https://manu60.magtech.com.cn/biotech/CN/Y2020/V40/I7/59

图1  2017年我国糖尿病患糖尿病、IGT的比例及人数统计,以及2045年患糖尿病、IGT的比例及人数的预测
图2  干细胞功能简介
细胞来源 诱导程序 基础培养基 诱导剂 培养天数 参考文献
第一步 无血清H-DMEM 0.5mmol/L β-巯基乙醇 2天 [20-21]
BM-MSCs 第二步 无血清H-DMEM 1%非必需氨基酸、20ng/ml β-FGF、2% B27,2mmol/L L-谷氨酰胺 8天
第三步 无血清H-DMEM 10ng/ml β-FGF、10ng/ml 激活素 A、2%B27、10mmol/L烟酰胺 8天
UC-MSCs 第一步 10%FBS H-DMEM 6mmol/L维甲酸 2天 [22]
第二步 10%FBS L-DMEM 10mmol/L烟酰胺、20ng/ml表皮生长因子 6天
第三步 10%FBS L-DMEM 10nmol/L 肠促胰岛素类似物-4 6天
ADSCs 一步法诱导 DMEM/F12 10mmol/L烟酰胺、2nmol/L 激活素-A、10nmol/L 肠促胰岛素类似物-4、100pmol/L HGF、10nmol/L五肽促胃酸激素、B27血清替代物、N-2添加剂 3天 [26-27]
表1  间充质干细胞体外诱导为产胰岛素细胞的过程
序列 细胞来源 回输细胞数量 受试者数 注射方式 随访时间 治疗效果 参考文献
1 HSC 11.0×106cells /kg 28 静脉 36个月 AUCc-pep↑, GAD↓, HbA1C↓,胰岛素需求量↓ [72]
2 BM-MNC 180×106cells /kg 3 肝穿刺 12个月 ICA、GAD、抗胰岛素抗体水平为阴性,C肽水平↑,HbA1c↓ [73]
3 UC-MSCs 2.6 ±1.2×107 cells 29 ─ 24个月 FPG↓,PPG↓,HbA1c↓,C肽水平↑,CPGR↑,胰岛素需求量↓ [74]
4 BM-MSC 2.75×106cells/kg 20 静脉 12个月 C肽水平↑或者─ [75]
5 AD-MSC and BM-HSC ─ 20 门脉+胸腺循环及皮下组织 24个月 HbA1c↓,C肽水平↑,胰岛素需求量↓,GAD↓ [29]
6 UC-MSCs and aBM-MNC 1.1×106cells /kg and 106.8×106cells /kg 42 胰背动脉 12个月 AUCc-pep↑,胰岛素面积↑,HbA1C↓,胰岛素需求量↓ [76]
表2  不同组织来源的干细胞对I型糖尿病的临床治疗效果统计
序列 细胞来源 细胞回输数量 受试者数 注射方式 随访时间 治疗效果 参考文献
1 BM-MSCs 3.5±1.4×108cells 10 12指肠 6个月 HbA1c↓, 胰岛素需求量↓ [77]
2 BM-MSCs 2.8 ± 1.9 × 109cells 118 胰背动脉 33个月 FPG↓,HbA1c↓,C肽水平↑,CPGR↑, 胰岛素需求量↓ [78]
3 UC-MSCs 1.0×106cells/kg 61 静脉 36个月 FPG↓,HbA1c↓,PPG↓, C肽水平↑,CPGR↑, HOMA-β↑,胰岛素需求量↓ [79]
4 UC-MSCs 1.8×106cells /kg 18 静脉 6个月 FPG↓,PPG↓,C肽水平↑, Tregs↑ [80]
5 PDSC 1.35×106cells /kg 10 静脉 3个月 胰岛素需求量↓,C肽水平↑ [81]
6 ADSCs NA 40 静脉 3个月 FPG↓,HbA1c↓,胰岛素需求量↓,C肽水平↑ [82]
表3  不同组织来源的干细胞对2型糖尿病的临床治疗效果统计
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