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铜（II）-黄芩素增强糖尿病患者干细胞的旁分泌作用和再生功能。

Cu(II)-baicalein enhance paracrine effect and regenerative function of stem cells in patients with diabetes.

作者信息

Liu Kaijing, Li Ruihao, Wang Shusen, Fu Xue, Zhu Ni, Liang Xiaoyu, Li Huiyang, Wang Xiaoli, Wang Le, Li Yongjun, Dai Jianwu, Yang Jing

机构信息

Key Laboratory of Advanced Medical Materials and Devices, Institute of Biomedical Engineering, Tianjin Institutes of Health Science, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin, 300192, China.

Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, China.

出版信息

Bioact Mater. 2024 Jul 2;36:455-473. doi: 10.1016/j.bioactmat.2024.03.013. eCollection 2024 Jun.

DOI:10.1016/j.bioactmat.2024.03.013
PMID:39055352
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11269795/
Abstract

The development of engineered or modified autologous stem cells is an effective strategy to improve the efficacy of stem cell therapy. In this study, the stemness and functionality of adipose stem cells derived from type 1 diabetic donors (T1DM-ASC) were enhanced by treatment with Cu(II)-baicalein microflowers (Cu-MON). After treatment with Cu-MON, T1DM-ASC showed enhanced expression of the genes involved in the cytokine-cytokine receptor interaction pathway and increased cytokine secretion. Among the top 13 differentially expressed genes between T1DM-ASC and Cu-MON-treated T1DM-ASC (CMTA), some genes were also expressed in HUVEC, Myoblast, Myofibroblast, and Vascular Smooth Muscle cells, inferring the common role of these cell types. In vivo experiments showed that CMTA had the same therapeutic effect as adipose-derived stem cells from non-diabetic donors (ND-ASC) at a 15% cell dose, greatly reducing the treatment cost. Taken together, these findings suggest that Cu-MON promoted angiogenesis by promoting the stemness and functionality of T1DM-ASC and influencing multiple overall repair processes, including paracrine effects.

摘要

工程化或修饰的自体干细胞的开发是提高干细胞治疗效果的有效策略。在本研究中，通过用Cu（II）-黄芩苷微花（Cu-MON）处理，增强了来自1型糖尿病供体的脂肪干细胞（T1DM-ASC）的干性和功能。用Cu-MON处理后，T1DM-ASC显示出参与细胞因子-细胞因子受体相互作用途径的基因表达增强，细胞因子分泌增加。在T1DM-ASC和经Cu-MON处理的T1DM-ASC（CMTA）之间的前13个差异表达基因中，一些基因也在人脐静脉内皮细胞、成肌细胞、肌成纤维细胞和血管平滑肌细胞中表达，这推断出这些细胞类型的共同作用。体内实验表明，在15%的细胞剂量下，CMTA与来自非糖尿病供体的脂肪干细胞（ND-ASC）具有相同的治疗效果，大大降低了治疗成本。综上所述，这些发现表明，Cu-MON通过促进T1DM-ASC的干性和功能以及影响包括旁分泌作用在内的多个整体修复过程来促进血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/212bf3d25819/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/9c8e75893a59/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/26cd80c7ff69/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/626960b68bee/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/e760bf8af186/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/a81974133692/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/ffc69dc840b6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/2802689656d0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/212bf3d25819/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/9c8e75893a59/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/26cd80c7ff69/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/626960b68bee/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/e760bf8af186/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/a81974133692/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/ffc69dc840b6/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/2802689656d0/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e16/11269795/212bf3d25819/gr7.jpg

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本文引用的文献

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Adv Healthc Mater. 2023 Feb;12(5):e2202010. doi: 10.1002/adhm.202202010. Epub 2022 Dec 3.
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Emerging principles of cytokine pharmacology and therapeutics.细胞因子药理学和治疗学的新兴原则。
Nat Rev Drug Discov. 2023 Jan;22(1):21-37. doi: 10.1038/s41573-022-00557-6. Epub 2022 Sep 21.
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Emerging roles of mesenchymal stem cell therapy in patients with critical limb ischemia.
间充质干细胞治疗在重症肢体缺血患者中的新作用。
Stem Cell Res Ther. 2022 Sep 6;13(1):462. doi: 10.1186/s13287-022-03148-9.
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Type 1 diabetes and engineering enhanced islet transplantation.1 型糖尿病与工程化胰岛移植。
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