天美传媒

Islet transplantation; Type 1 diabetes; Mesenchymal stromal cells; Graft survival; Immune modulation; Beta-cell function; Glycemic stability; Regenerative therapy; Transplant immunology; Cellular therapy

Introduction

Type 1 diabetes mellitus is characterized by autoimmune destruction of pancreatic beta cells, leading to lifelong dependence on exogenous insulin. While intensive insulin therapy and modern glucose monitoring systems have improved glycemic control, achieving physiological insulin secretion remains a major challenge. Islet transplantation has emerged as a promising therapeutic option for select patients with Type 1 diabetes who experience frequent severe hypoglycemia or poor glycemic control despite optimal therapy. However, long-term success is limited by immune rejection, islet cell death, and gradual loss of graft function. Recent studies suggest that mesenchymal stromal cells (MSCs), due to their immunomodulatory and regenerative properties, may improve islet engraftment, enhance graft survival, and reduce the need for long-term immunosuppression. This study evaluates the long-term outcomes of MSC-enriched islet transplantation, focusing on graft survival, glycemic stability, and insulin independence in patients with Type 1 diabetes.

Discussion

The prospective, multi-center study included 25 adults with long-standing Type 1 diabetes who underwent allogeneic islet transplantation combined with autologous or donor-derived MSCs. Patients were followed for a median of five years post-transplantation. MSCs were co-infused with isolated pancreatic islets via the portal vein and were characterized prior to transplantation for viability, phenotype, and cytokine secretion profile. The patients were monitored for insulin requirements, HbA1c, C-peptide levels, glucose variability, and adverse events related to the transplantation or immunosuppression.

At one-year follow-up, 72% of the participants maintained partial graft function (defined as C-peptide positivity and reduced insulin needs), and 40% achieved full insulin independence. At five years, 56% retained graft function, with 28% still insulin-free. Glycemic control improved significantly, with mean HbA1c decreasing from 8.5% pre-transplant to 6.3% at five years. CGM data showed reduced glycemic variability and improved time-in-range. The MSC-treated group showed lower levels of pro-inflammatory cytokines (e.g., IL-6, TNF-alpha) and increased regulatory T-cell markers, suggesting enhanced immune tolerance. Adverse events were minimal, with no serious transplant-related complications. Mild liver enzyme elevations and transient fatigue were noted in a few cases, likely related to portal infusion and immunosuppressive regimens.

The supportive role of MSCs was evident in improved islet vascularization and reduced peritransplant inflammation, as observed in biopsy and imaging studies. Additionally, the need for intensive immunosuppression was reduced, with several patients maintained on low-dose tacrolimus and mycophenolate alone. Quality of life scores improved significantly, and psychological assessments indicated reduced diabetes distress and treatment burden. While promising, the study also emphasized the need for standardized MSC sourcing, dosing, and delivery protocols to ensure reproducibility and safety across broader populations.

Conclusion

MSC-enriched islet transplantation offers a promising strategy to enhance graft survival and achieve long-term glycemic stability in patients with Type 1 diabetes. The immunomodulatory and regenerative benefits of MSCs improve islet engraftment and function while reducing the intensity of immunosuppression required. This approach has the potential to shift islet transplantation from an experimental therapy to a more mainstream option for selected patients. Despite the encouraging results, larger controlled trials, long-term safety monitoring, and cost-effectiveness evaluations are essential to confirm the clinical utility of MSC-based cellular therapies. As the field of regenerative medicine continues to evolve, combining islet transplantation with supportive cell therapies may become a cornerstone in the quest for a functional cure for Type 1 diabetes.

References

1. Sackett DL, Haynes BR, Tugwell P, Guyatt GH (1991) . London: Lippincott, Williams and Wilkins.

2. Mullan F (1984) . Public Health Rep 99: 442–445.

   ,

3. Mullan F, Nutting PA (1986) . Fam Med 18: 221–225.

   ,

4. Abramson JH (1984) . Public Health Rep 99: 437–441.

   ,

5. Hart JT (1974) . J R Coll Physicians Lond 8: 299–314.

   ,

6. Pickles WN (1939) . Bristol: John Wright and Sons.

7. Fry J (1979) . Lancaster: MT Press.

8. Hodgkin K (1985) . Churchill Livingstone.

9. Last RJ (2001) . Oxford: International Epidemiological Association.

10. Kroenke K (1997) . J Gen Intern Med 12: 509–510.