Immune regulation: the main mechanism of stem cell treatment of diabetes

Immune regulation: The main mechanism of stem cell treatment of diabetes. Stem cells have become an important topic in the treatment of diabetes. At this stage, results have been achieved in preclinical and clinical trials.

Chronic inflammation is not only a complication caused by diabetes, but also an important factor that promotes the occurrence and development of diabetes. Epidemiological statistics show that 80% of diabetic patients are accompanied by chronic inflammation, which is local or throughout the body. Obvious pro-inflammatory cell infiltration can be seen in fat, muscle and other tissues, IL-6, C-reactive protein and other inflammations. Sex cytokines increase, produce insulin resistance, destroy pancreatic β cells, and insufficient insulin secretion.

The influence of inflammation-related cells and cytokines in body tissues on diabetes was not discovered until 2003. Immune cells (such as macrophages, Th cells, Tregs cells, etc.) and cytokines are involved in the induction of diabetes, making immune regulation a One of the potential therapeutic targets of diabetes.

In recent years, studies have found that stem cells can exert a comprehensive immune regulation function, which can inhibit non-specific immune responses, but also inhibit specific immune responses, and improve the inflammatory microenvironment. Stem cells have become an important topic in the treatment of diabetes. Results have been achieved in clinical trials.

1. Basic research

Krampera et al. found that stem cells can inhibit the proliferation of CD4+ and CD8+ lymphocytes, and eliminate the response of memory T cells to antigens; Bartholomew et al. verified that stem cells can inhibit the proliferation of T cells and reduce CD25, CD38, and CD69 on the surface of lymphocytes stimulated by PHA The expression of other activation markers. It is preliminarily believed that stem cells can directly inhibit the proliferation and activation of T cells, inhibit the initiation of immune responses, and then exert an immunosuppressive effect in the inflammatory environment of diabetes.

In addition to direct inhibition, the researchers also discovered that stem cells can also indirectly act on T cells by secreting cytokines. Davies et al. found that stem cells inhibit the activation of CD4+ T cells and the secretion of IL-2 by T cells by secreting programmed death receptor 1 (PD-1) ligand, and induce irreversible T cell hyporesponsiveness and death; Factors such as TGF-β, HGF and PGE-2 also play a key role in the immune suppression of stem cells.

2. Animal research

Zhou et al.’s research on animal models found that stem cell transplantation can significantly reduce the inflammatory response in diabetic model mice. In the stem cell group, the random blood glucose concentration was reduced by (25.0±0.1)%, insulin secretion and M2 macrophages increased, and M2 macrophages The percentage increased from (22.5±4.0)% to (72.5±3.4)%; the levels of inflammatory factors IL-1β, IL-6, IL-12 and TNF-α mRNA levels were significantly reduced, and the anti-inflammatory factors IL-10, IL-4 and TGF -βmRNA levels are significantly increased.

Many studies have explored the immunomodulatory effects of stem cells on diabetes. The results show that stem cell infusion reduces the number of Th1 cells and the secretion of IFN-γ, while increasing the proportion of regulatory T cells. Stem cells improve the inflammatory microenvironment of model mice to improve insulin resistance, prevent the continued destruction of pancreatic β cells, reduce high blood sugar concentration, and provide new clinical ideas for diabetes.

3. Clinical research

The researchers used umbilical cord mesenchymal stem cell intravenous injection combined with transcatheter pancreatic injection to treat 22 diabetic patients. The results showed that the patient’s C-peptide level and pancreatic β-cell function improved, and the amount of insulin was reduced, which is believed to be related to the improvement of systemic inflammation/immunological regulation .

Result analysis: HbA1c of patients after stem cell transplantation decreased from 8.2% at baseline to 6.89% after 3 months, and HbA1c remained stable at 7.0% at 12 months of follow-up; it was higher after fasting C-peptide treatment than before treatment. Fasting C-peptide levels are related to the decrease in the number of CD3+ T lymphocytes; the levels of systemic inflammation markers and T lymphocyte counts are decreased, and the levels of pro-inflammatory cytokines including IL-6 and IL-1β are significantly decreased . There is a significant correlation between fasting C-peptide and IL-6 levels, which suggests that reduced systemic inflammation may play an important role in improving basal insulin secretion

(sourceinternet, reference only)

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