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In the Clinical Guidelines for Prevention and Control of Type 2 Diabetes Mellitus in the Elderly in China (2022 Edition), there is a set of statistics about type 2 diabetes in China: in 2020, the elderly population (≥60 years old) in China accounted for 18.7% (260.4 million) of the total population, of which about 30% suffered from diabetes, and T2DM accounted for more than 95% of the total population. Diabetes mellitus is a metabolic disease characterised by hyperglycaemia, with type 1 diabetes mellitus and type 2 diabetes mellitus (T2DM patients) predominating.

Unlike type 1 diabetes mellitus, which is characterised by absolute impairment of pancreatic islet function and absolute insulin deficiency, patients with T2DM are characterised by progressive and unavoidable β-cell reduction and dysfunction and insulin resistance, which is the main clinical type of diabetes mellitus in China at present.

In recent years stem cells and stem cell therapies with high differentiation capacity have entered the field of vision of doctors and researchers and are developing rapidly in the field of T2DM treatment. Among them, foetal placenta and umbilical cord-derived mesenchymal stem cells (PD-MSC/hUC-MSC) have greater differentiation potential than other common mesenchymal stem cell types, and they are currently the most applied cells in T2DM therapy. There have been more research and application reports from abroad, but the practical application of PD-MSC/hUC-MSC in the treatment of T2DM in China is still in its infancy, and we are following up some recent clinical application practices to understand its efficacy in practical application.

hUC-MSC

Effectiveness in the treatment of T2DM

In 2022, the First Medical Centre of the Chinese People's Liberation Army (PLA) conducted a large sample size study on the efficacy and safety evaluation of umbilical cord mesenchymal stem cell therapies in Chinese adult T2DM patients [1]. In this single-centre, double-blind, randomized, placebo-controlled trial, 91 patients were randomly assigned to receive UC-MSCs. One treatment group (n = 45) received a placebo treatment group (n = 46).

Patients were treated with intravenous infusions of UC-MSCs at 4-week intervals, and a total of 3 UC-MSCs treatments were given, with a total of 1 × 106/kg of UC-MSCs per intravenous infusion, and a follow-up period of 48 weeks.At 48 weeks, 20% of the patients in the UC-MSCs group and 4.55% of the patients in the placebo group achieved a therapeutic effect, with a glycated haemoglobin (HbA1c) level of <7.0%, a daily insulin requirement was reduced by ≥50% (P < 0.05).

The percentage reduction in daily insulin requirement was also significantly higher in the UC-MSCs group than in the placebo group (27.78%: 15.62%, P < 0.05).The patients in the UC-MSCs group had a significant reduction in HbA1c levels compared to the placebo group, and there were no associated major adverse events in the UC-MSCs transplant group. The results of this study demonstrate the efficacy and safety of UC-MSCs transplantation for the treatment of T2DM.
 

Figure 1: Insulin requirements of patients after treatment with UC-MSCs or placebo.Patients in the UC-MSCs group (black bars) had significantly lower insulin requirements than those in the placebo group (grey bars) [1].

PD-MSC

Effectiveness in the treatment of T2DM

A study from the National Stem Cell Engineering Research Centre of the Institute of Haematology, Chinese Academy of Sciences and Beijing Medical University [2] administered three intravenous infusions of PD-MSC at a dose of 1.35×106/kg per infusion to 10 patients with a history of long-standing T2DM, with an interval of 1 month between each of the three infusions, and all patients were followed up for at least 3 months after treatment.

The average daily insulin level of the 10 patients decreased from 63.7±18.7 to 34.7±13.4 IU (p<0.01), and C-peptide level increased from 4.1±3.7 ng/mL to 5.6±3.8 ng/mL (p<0.05), and 4 out of the 10 responders experienced more than 50% reduction of insulin dose after stem cell infusion, and stem cell therapy also simultaneously reduced the The stem cell therapy also reduced the incidence of diabetic complications, including diabetic retinopathy, neuropathy and nephropathy, and no fever, chills, liver damage or other side effects were observed in the stem cell transplant group. Similar findings have been reported in several similar studies at other hospitals [3,4].

Insulin levels at all time points after treatment were higher than before treatment, and the difference was statistically significant. *p<0.01

C-peptide levels were higher at all time points after treatment than before treatment, and the difference was statistically significant. *p<0.05

There was a statistically significant decrease in insulin dosage after treatment, and the difference was statistically significant. *p<0.01

There was a statistically significant decrease in insulin dosage after treatment, and the difference was statistically significant. *p<0.01

PD-MSC/hUC-MSC

Relevant mechanisms in the treatment of T2DM

In most of the studies MSC were administered by peripheral intravenous injection, which is easier to administer and has fewer adverse effects, especially in multiple injection regimens. MSC therapy may be an emerging and very promising treatment modality for patients with diabetes, especially type 2 diabetes. The mechanism of action of PD-MSC/hUC-MSC in T2DM treatment is also being improved, which may be closely related to the following mechanisms:

(1) MSC have the potential to differentiate into insulin-producing cells and repair pancreatic β-cells;

(2) MSC can restore glucose transporter proteins on cell membranes of skeletal muscle, liver and adipose tissue;

(3) MSC attenuate inflammatory responses such as insulin resistance and pancreatitis by producing IL6;

(4) MSC modulate immune cell function and regulate hepatic glucose metabolism.

With the declining ethical controversy of stem cell therapy and the increasing acceptance of stem cell therapy, it is believed that this treatment will benefit more and more diabetic patients.