Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell transplantation in type 2 diabetes: a pilot clinical trial.

BACKGROUND

Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction, with chronic inflammation playing a central pathogenic role. Mesenchymal stem cells (MSCs) possess therapeutic potential through immunomodulatory and tissue-reparative properties. This study aimed to evaluate the safety and efficacy of intravenous allogeneic umbilical cord-derived MSCs (UC-MSCs) in patients with T2DM.

METHODS

Eleven adults with T2DM (disease duration ≥ 10 years; HbA1c ≤ 8%) received a single intravenous infusion of 1 × 108 UC-MSCs. This open-label pilot trial assessed safety (adverse events, hematologic and metabolic parameters) and efficacy (glycemic control and inflammatory gene expression) over a 2-month follow-up period. UC-MSCs were isolated under standardized conditions.

RESULTS

UC-MSC transplantation in patients with T2DM was well tolerated, with only transient fever (36.3%) and mild muscle pain (18.2%) reported. The intervention resulted in significant metabolic improvements, including a 2.1% reduction in HbA1c (P = 0.00095) and a decrease in fasting glucose by 93.7 mg/dL (P = 0.00097). Treatment also modulated inflammatory pathways, as evidenced by upregulating of IKBα (1.76-fold, P = 0.0067) and downregulating of TNFα (0.62-fold) and IL-6 (0.65-fold). Variability in IKBα expression accounted for 48% of the variance in HbA1c (r = -0.69). Two distinct response patterns were observed: improvement in insulin sensitivity (7/11) via NF-κB suppression, and enhancement of β-cell function (3/11).

CONCLUSION

Allogeneic UC-MSC transplantation appears safe and significantly improves glycemic control in patients with T2DM. The heterogeneity in patient responses underscores the importance of stratification based on inflammatory status. These findings support UC-MSC therapy as a promising disease-modifying strategy and highlight the need for larger, controlled clinical trials.