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

• Published in: Bioactive materials 2024-06, Vol.36, p.455-473
• Main Authors: Liu, Kaijing, Li, Ruihao, Wang, Shusen, Fu, Xue, Zhu, Ni, Liang, Xiaoyu, Li, Huiyang, Wang, Xiaoli, Wang, Le, Li, Yongjun, Dai, Jianwu, Yang, Jing
• Format: Article
• Language: English
• Subjects: Adipose stem cells; Angiogenesis; Paracrine effect; Regenerative function; Type 1 diabetes mellitus
• ISSN: 2452-199X; 2452-199X
• DOI: 10.1016/j.bioactmat.2024.03.013

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. [Display omitted] •The quality of adipose stem cells in diabetic patients was significantly improved by Cu-MON pretreatment, and the secretion of cytokines almost reached the level of healthy people, all this means that standardisation of stem cell quality is possible.•The expression of VEGF, EGF, bFGF and other angiogenesis-related cytokines is increased, and the expression of oncogenes is down-regulated, which favourably promotes therapeutic angiogenesis in mice with critical limb ischemia and reduces the carcinogenic risk of stem cells. And relevant mechanisms was also explored.•Directed induction of macrophage polarization from M1 phenotype to M2 phenotype created a microenvironment conducive to tissue repair, and P13K-Akt signaling pathway, thus simulating the body's self-healing mechanism and promoting tissue repair and regeneration.•The increased ability of stem cells to resist adverse external environments, such as the pathological microenvironment due to reactive oxygen species in vivo, means that the viability of stem cells after transplantation in vivo is increased. As a result, the number of adipose stem cells used for transplantation was only 15% of the conventional cell therapy dose and efficient therapeutic angiogenesis was still achieved in mice with critical limb ischemia, which greatly reducing the treatment cost.