Stem Cell Therapy for Immune-Mediated Diseases: Mechanisms and Clinical Applications
Introduction Immune-mediated diseases, including autoimmune disorders, inflammatory syndromes, and immune dysregulation syndromes, pose significant challenges due to their chronic progression, multisystem involvement, and limited curative options. Current therapies—such as corticosteroids, disease-modifying antirheumatic drugs (DMARDs), and biologics—can suppress immune activity but often result in side effects and incomplete remission. Stem cell–based therapies have emerged as a promising alternative by reprogramming immune responses, repairing tissue damage, and restoring immune homeostasis.
Stem Cell Therapy for Immune-Mediated Diseases: Mechanisms and Clinical Applications
3/5/20192 min read
Mechanistic Basis of Stem Cell Therapy in Immune Diseases
1. Immunomodulation
Mesenchymal stem cells (MSCs) suppress overactive immune responses by inhibiting Th1 and Th17 cells while promoting regulatory T cells (Tregs).
MSCs regulate antigen-presenting cells, dendritic cells, and B cells, reducing autoantibody production.
Exosomes from stem cells carry microRNAs that fine-tune immune signaling pathways.
2. Anti-Inflammatory Effects
Stem cells secrete cytokines (e.g., IL-10, TGF-β, PGE2) that reduce pro-inflammatory mediators (TNF-α, IL-1β, IFN-γ).
They shift macrophages from the pro-inflammatory M1 phenotype to the tissue-repairing M2 phenotype.
3. Tissue Repair and Regeneration
Chronic autoimmune diseases (e.g., lupus nephritis, multiple sclerosis) cause irreversible tissue damage.
Stem cells promote angiogenesis, anti-apoptosis, and matrix remodeling, facilitating organ repair.
4. Immune Tolerance Induction
Hematopoietic stem cell transplantation (HSCT) reconstitutes the entire immune system, inducing long-term remission in severe autoimmune diseases.
MSCs create a tolerogenic immune microenvironment, restoring immune self-recognition.
Stem Cell Types for Immune Disorders
Mesenchymal Stem Cells (MSCs)
Sources: bone marrow, umbilical cord, adipose tissue.
Applications: rheumatoid arthritis, systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), psoriasis.
Hematopoietic Stem Cells (HSCs)
Used in autologous or allogeneic transplantation to “reset” the immune system.
Established in severe multiple sclerosis, systemic sclerosis, and refractory autoimmune cytopenias.
Induced Pluripotent Stem Cells (iPSCs)
Potential to generate patient-specific immune cells and tolerogenic dendritic cells.
Still in early translational stages.
Stem Cell–Derived Exosomes
Cell-free therapy, avoiding risks of engraftment or tumorigenesis.
Effective in preclinical models of rheumatoid arthritis and colitis.
Clinical Applications
Rheumatoid Arthritis (RA): MSC infusions reduce joint inflammation, improve DAS28 scores, and enhance cartilage repair.
Systemic Lupus Erythematosus (SLE): Umbilical cord MSCs show efficacy in refractory lupus nephritis, reducing proteinuria and systemic inflammation.
Multiple Sclerosis (MS): HSCT demonstrates long-term remission in aggressive MS; MSCs are being tested for neuroprotection and repair.
Inflammatory Bowel Disease (IBD): Local injection of MSCs promotes mucosal healing in Crohn’s disease fistulas.
Type 1 Diabetes (T1DM): Stem cell therapies aim to restore immune tolerance to β-cells, protecting residual pancreatic function.
Conclusion
Stem cell therapy provides a multi-dimensional approach for immune-mediated diseases by combining immune rebalancing, anti-inflammatory effects, and tissue regeneration. While challenges remain in standardization, dosing, and long-term safety, clinical evidence continues to expand. Stem cells hold the potential to shift treatment paradigms from symptomatic immunosuppression to immune restoration and durable remission.
中文版本
干细胞在免疫类疾病治疗中的作用机制与临床应用
引言
免疫相关疾病包括 自身免疫性疾病、炎症性疾病以及免疫失调综合征，其特点是病程慢性化、多系统损伤、治疗困难。现有治疗方式（如糖皮质激素、DMARDs、生物制剂）主要抑制免疫反应，但常伴随副作用，且难以实现长期缓解。干细胞疗法近年来逐渐成为新兴方向，能够通过 免疫重建、组织修复与免疫稳态恢复，为临床带来突破性可能。
干细胞在免疫疾病中的作用机制
1. 免疫调控
间充质干细胞（MSCs） 可抑制过度活化的 Th1/Th17 细胞，促进 调节性T细胞（Tregs） 增殖。
MSCs 调节树突状细胞、B细胞功能，减少自身抗体生成。
干细胞外泌体中的microRNA可精细调控免疫信号通路。
2. 抗炎作用
干细胞分泌 IL-10、TGF-β、PGE2 等，抑制 TNF-α、IL-1β、IFN-γ 等炎症因子。
调控巨噬细胞由 M1型（炎症型） 向 M2型（修复型） 转化。
3. 组织修复与再生
慢性自身免疫病（如狼疮性肾炎、多发性硬化）往往导致器官损伤。
干细胞通过 促进血管生成、抗凋亡、基质重建，实现组织修复。
4. 免疫耐受诱导
造血干细胞移植（HSCT） 可重建免疫系统，实现部分重症自身免疫病的长期缓解。
MSCs 创造耐受性免疫微环境，恢复机体自我识别。
应用于免疫疾病的干细胞类型
间充质干细胞（MSCs）
来源：骨髓、脐带、脂肪。
应用：类风湿关节炎、系统性红斑狼疮（SLE）、炎症性肠病、银屑病。
造血干细胞（HSCs）
自体或异体移植，用于“重置”免疫系统。
已在多发性硬化、系统性硬化症、顽固性免疫性血细胞减少症中应用。
诱导多能干细胞（iPSCs）
可生成患者特异性免疫细胞与耐受性树突状细胞。
仍处于早期转化研究阶段。
干细胞外泌体
属于“无细胞疗法”，规避移植排斥或致瘤风险。
在类风湿关节炎、结肠炎动物模型中显示良好疗效。
临床应用进展
类风湿关节炎（RA）：MSC输注可缓解关节炎症、改善DAS28评分、促进软骨修复。
系统性红斑狼疮（SLE）：脐带MSCs在难治性狼疮性肾炎中显著改善蛋白尿与炎症指标。
多发性硬化（MS）：HSCT已在部分患者中实现长期缓解；MSC疗法正在探索神经保护作用。
炎症性肠病（IBD）：MSC局部注射促进克罗恩病瘘管愈合。
1型糖尿病（T1DM）：干细胞疗法旨在恢复对胰岛β细胞的免疫耐受，保护残余功能。
结论
干细胞为免疫类疾病提供了 多维度的治疗手段，既能 重建免疫平衡、抑制炎症反应，又能促进组织修复。相比传统免疫抑制疗法，干细胞疗法更具根源性和持久性。尽管标准化、剂量与长期安全性仍需进一步验证，但已有临床证据表明其巨大潜力。未来，干细胞有望成为免疫疾病治疗的 核心疗法。