Stem Cells in the Treatment of Immune-Mediated Diseases

Mechanisms of Action

1. Immune Modulation

   • MSCs interact with both innate and adaptive immune cells.

   • They inhibit T-cell proliferation, shift the balance from pro-inflammatory Th1/Th17 cells toward regulatory T cells (Tregs), and suppress B-cell activation (Uccelli et al., 2008; Wang et al., 2014).

2. Anti-Inflammatory Effects

   • MSCs secrete cytokines such as IL-10, TGF-β, and prostaglandin E2 (PGE2) to reduce systemic inflammation and local tissue damage.

   • They can modulate macrophage polarization toward the anti-inflammatory M2 phenotype, reducing chronic inflammation (Németh et al., 2009).

3. Tissue Repair and Regeneration

   • Beyond immunomodulation, MSCs can differentiate into mesodermal lineage cells (e.g., osteoblasts, chondrocytes, adipocytes) and secrete trophic factors that support tissue repair in organs damaged by autoimmune attacks (Le Blanc & Mougiakakos, 2012).

4. Exosome-Mediated Immune Regulation

   • Stem cell-derived extracellular vesicles carry microRNAs and proteins that influence immune signaling pathways, offering cell-free immunotherapy options with reduced risk of tumorigenicity (Phinney & Pittenger, 2017).

Clinical Evidence

• Rheumatoid Arthritis (RA):

  • Autologous or allogeneic MSC infusion has been shown to reduce joint inflammation, decrease autoantibody levels, and improve functional outcomes in phase I/II studies (Wang et al., 2013).

• Systemic Lupus Erythematosus (SLE):

  • Umbilical cord-derived MSC transplantation improved disease activity scores, reduced proteinuria, and restored Treg/Th17 balance in refractory patients (Sun et al., 2010; Liang et al., 2019).

• Multiple Sclerosis (MS):

  • Intravenous MSCs have shown safety and potential efficacy in slowing neurological deterioration and reducing MRI lesions in early-phase trials (Bonab et al., 2007; Connick et al., 2012).

Conclusion

Stem cell therapy offers a multi-modal, disease-modifying approach for immune-mediated diseases by modulating immune responses, reducing inflammation, and promoting tissue repair. While long-term efficacy requires further large-scale trials, current clinical studies demonstrate promising safety and preliminary effectiveness, particularly for patients with refractory autoimmune conditions.

Key References:

1. Uccelli A, et al. Mesenchymal stem cells in health and disease. Nat Rev Immunol. 2008;8:726–736.

2. Wang D, et al. Mesenchymal stem cells in autoimmune disease treatment. Clin Rev Allergy Immunol. 2014;46:211–224.

3. Németh K, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages. Nat Med. 2009;15:42–49.

4. Le Blanc K, Mougiakakos D. Multipotent mesenchymal stromal cells and the innate immune system. Nat Rev Immunol. 2012;12:383–396.

5. Sun L, et al. Umbilical cord mesenchymal stem cell transplantation in SLE. Arthritis Rheum. 2010;62:2467–2475.

6. Connick P, et al. Autologous mesenchymal stem cells for multiple sclerosis. Lancet Neurol. 2012;11:150–156.

中文版本 — 干细胞在免疫性疾病治疗中的作用

引言
免疫性疾病（包括类风湿性关节炎、系统性红斑狼疮、多发性硬化等自身免疫病）是由于免疫系统异常攻击自身组织而引起的。传统治疗（如糖皮质激素、免疫抑制剂）可缓解症状，但无法恢复免疫平衡，且可能带来全身副作用。

干细胞疗法，尤其是间充质干细胞（MSCs），因其能够调节免疫系统、促进组织修复、恢复免疫耐受，成为近年来免疫疾病研究的热点。

作用机制

1. 免疫调节

   • MSCs可与先天及适应性免疫细胞相互作用。

   • 抑制T细胞增殖，促使Th1/Th17向调节性T细胞（Tregs）转化，抑制B细胞活化（Uccelli et al., 2008; Wang et al., 2014）。

2. 抗炎作用

   • MSCs分泌IL-10、TGF-β、PGE2等因子，减少全身及局部炎症损伤。

   • 调节巨噬细胞向抗炎M2型极化，降低慢性炎症（Németh et al., 2009）。

3. 组织修复与再生

   • MSCs可分化为间充质来源细胞（骨细胞、软骨细胞、脂肪细胞），并分泌促生长因子，帮助修复自身免疫攻击造成的组织损伤（Le Blanc & Mougiakakos, 2012）。

4. 外泌体介导免疫调节

   • 干细胞外泌体携带miRNA和蛋白质，影响免疫信号通路，为无细胞免疫治疗提供新途径，并降低肿瘤风险（Phinney & Pittenger, 2017）。

临床研究证据

• 类风湿性关节炎（RA）

  • 自体或异体MSC输注可减轻关节炎症、降低自身抗体水平，并改善功能状态（Wang et al., 2013）。

• 系统性红斑狼疮（SLE）

  • 脐带来源MSC移植改善疾病活动度、降低蛋白尿，并恢复Treg/Th17平衡，尤其对难治性患者有效（Sun et al., 2010; Liang et al., 2019）。

• 多发性硬化（MS）

  • 静脉输注MSC安全性良好，可减缓神经功能恶化，并减少MRI病灶（Bonab et al., 2007; Connick et al., 2012）。

结论

干细胞疗法为免疫性疾病提供了多机制、可能改变病程的治疗方案，通过免疫调节、抗炎、促进组织修复改善患者健康。虽然长期疗效仍需大规模临床验证，但现有研究显示其安全性良好，并对难治性患者具有潜在疗效。