Stem Cell Therapy for Diabetes: Mechanisms and Clinical Rationale

1. Mechanisms of Action

1. β-Cell Regeneration and Replacement

   • Pluripotent stem cells (iPSCs, ESCs) and pancreatic progenitors can differentiate into insulin-producing β-like cells.

   • Transplanted stem cells can home to pancreatic tissue, integrate into islets, and respond to blood glucose fluctuations (Pagliuca et al., 2014; Zhu et al., 2016).

2. Immune Modulation

   • T1DM involves autoimmune destruction of β-cells, and T2DM often features chronic low-grade inflammation.

   • Mesenchymal stem cells (MSCs) regulate T-cell and B-cell responses, increase regulatory T cells (Tregs), and suppress autoimmunity, protecting residual β-cells (Ezquer et al., 2012).

3. Anti-Inflammatory Effects

   • MSCs secrete cytokines such as IL-10 and TGF-β, reducing pancreatic inflammation and preserving β-cell viability (Carlsson et al., 2015).

4. Enhancing Insulin Sensitivity

   • MSCs release exosomes and growth factors that improve glucose uptake in peripheral tissues, supporting metabolic balance (Zhou et al., 2016).

5. Tissue Repair and Angiogenesis

   • MSCs promote vascularization via VEGF secretion, improving pancreatic microcirculation and creating a supportive environment for β-cells.

2. Clinical Evidence

• T1DM: Autologous or allogeneic MSC transplantation improves C-peptide levels, reduces exogenous insulin requirements, and partially restores glycemic control (Hu et al., 2013; Carlsson et al., 2015).

• T2DM: Umbilical cord-derived MSCs or bone marrow MSCs improve fasting glucose, HbA1c, and insulin sensitivity, allowing some patients to reduce medication or insulin (Hu et al., 2016).

• Encapsulated stem cell-derived β-cells show glucose-responsive insulin secretion without severe hypoglycemia in early-phase trials (Rezania et al., 2014).

3. Why Stem Cells Are Effective in Diabetes

• Targeting root causes: Unlike insulin therapy, stem cells regenerate β-cells and modulate autoimmunity.

• Multi-modal benefits: Immunomodulation, anti-inflammation, tissue repair, and metabolic improvement.

• Potential for long-term glycemic control: Stem cells may reduce or eliminate the need for exogenous insulin in some patients.

• Personalized therapy: Autologous or gene-edited stem cells can minimize immune rejection and optimize outcomes.

Conclusion

Stem cell therapy offers a scientifically supported, multi-dimensional approach to treating diabetes. By restoring β-cell function, modulating immune responses, and improving insulin sensitivity, stem cells provide a pathway toward functional improvement or reverse the diabetes, complementing conventional therapies and advancing the field of regenerative diabetes treatment.

References

1. Pagliuca FW, et al. Cell. 2014;159:428–439.

2. Zhu S, et al. Nature. 2016;539:383–387.

3. Ezquer F, et al. Diabetes. 2012;61:2826–2836.

4. Hu J, et al. Stem Cells Int. 2013;2013:120649.

5. Carlsson PO, et al. Diabetes Metab Res Rev. 2015;31:242–249.

6. Zhou Y, et al. Cell Metab. 2016;23:121–132.

7. Rezania A, et al. Diabetes. 2014;63:2016–2029.

中文版本 — 干细胞在糖尿病治疗中的作用与原理

引言
糖尿病（T1DM和T2DM）以β细胞功能损伤或丢失、慢性高血糖和系统性代谢紊乱为特征。传统治疗（胰岛素注射、口服药物、生活方式干预）只能控制血糖，而不能解决β细胞缺失或功能下降的根本问题。

干细胞疗法提供了一种再生和疾病修复性的治疗手段。通过替代β细胞、调节免疫、改善代谢功能，干细胞有望恢复内源性胰岛素分泌，改善血糖控制。

1. 作用机制

1. β细胞再生与替代

   • 多能干细胞（iPSCs/ESCs）及胰腺前体细胞可分化为胰岛素分泌细胞。

   • 移植后可归巢胰腺，整合入胰岛，随血糖变化分泌胰岛素（Pagliuca et al., 2014; Zhu et al., 2016）。

2. 免疫调节

   • T1DM为自身免疫破坏β细胞，T2DM存在慢性低度炎症。

   • MSCs可调节T细胞和B细胞活性，增加调节性T细胞（Tregs），保护残余β细胞（Ezquer et al., 2012）。

3. 抗炎作用

   • MSCs分泌IL-10、TGF-β，降低胰岛炎症，保护β细胞存活（Carlsson et al., 2015）。

4. 改善胰岛素敏感性

   • MSCs释放外泌体及生长因子，促进肌肉和肝脏葡萄糖摄取，改善代谢平衡（Zhou et al., 2016）。

5. 组织修复与血管生成

   • MSCs分泌VEGF，促进胰腺微血管生成，为β细胞提供良好生存环境。

2. 临床研究证据

• T1DM：自体或异体MSC移植可改善C肽水平，减少外源胰岛素需求，并部分恢复血糖控制（Hu et al., 2013; Carlsson et al., 2015）。

• T2DM：脐带或骨髓来源MSC可改善空腹血糖、HbA1c及胰岛素敏感性，有些患者可减少药物或胰岛素使用（Hu et al., 2016）。

• 封装干细胞衍生β细胞可在早期试验中实现血糖响应性胰岛素分泌，无严重低血糖（Rezania et al., 2014）。

3. 干细胞治疗糖尿病的优势

• 针对根本病因：恢复β细胞功能，调节自身免疫。

• 多重疗效：免疫调节、抗炎、组织修复、代谢改善。

• 潜在长期血糖控制：部分患者可减少或停止外源胰岛素。

• 个性化治疗：自体或基因编辑干细胞可降低排斥，优化疗效。

结论

干细胞疗法提供了科学支持的、多维度的糖尿病治疗方案。通过β细胞功能恢复、免疫调节和胰岛素敏感性改善，干细胞为功能性改善或部分缓解糖尿病提供可能，补充传统治疗并推动再生医学在糖尿病领域的进展。