Potential immunomodulatory effects and combined application of adipose-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells

doi:10.3877/cma.j.issn.2095-1221.2025.04.005

Abstract

Abstract:

Adipose-derived mesenchymal stem cells (ADMSCs) and bone marrow-derived mesenchymal stem cells (BMSCs), as crucial sources of adult stem cells, exhibiting significant potential in the fields of immunomodulation and tissue repair. This article systematically reviews the regulatory mechanisms of ADMSCs and BMSCs on T cells (Th1/Th2/Th17/Treg), B cells, dendritic cells, macrophages, and natural killer (NK) cells, elucidating their shared and distinct characteristics in immunosuppressive pathways. Their spatiotemporal synergistic effects significantly enhance therapeutic efficacy, while heterologous cell combination therapy faces biosafety challenges. Furthermore, this study proposes a standardized quality control system and dynamic dosage regulation strategy, providing a theoretical foundation and translational pathway for optimizing stem cell therapy.

Key words: Bone marrow-derived mesenchymal stem cells, Adipose-derived mesenchymal stem cells, Immunomodulation, Stem cell therapy

Muyun Liu, Kaixiang Hou, Qipeng Han, Shihui Cui, Dianhua Wei, Yeyou Fu, Guanyan Ding, Liping Cong, Xiao Liang, Gang An. Potential immunomodulatory effects and combined application of adipose-derived mesenchymal stem cells and bone marrow-derived mesenchymal stem cells[J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2025, 15(04): 220-228.

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References 88

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免疫细胞类型	作用机制	涉及的因子/分子	功能效果
CD4⁺ T细胞	直接抑制增殖：抑制IL-2分泌及自然杀伤细胞活性；上调CD4⁺ CD25⁺ Treg细胞，抑制IFN-γ、IL-4等促炎因子^[13]；在炎症环境中促进IL-17产生^[11]	TGF-β、Foxp3、IL-2、IFN-γ、IL-4、IL-17^[9]	抑制T细胞活化^[10]和炎症反应^[9]，促进免疫耐受
Th1/Th2细胞	降低IL-17、IL-22、IFN-γ、TNF-α水平；抑制CD4⁺ T细胞向Th1分化；增加Th2细胞数量，改变Th1/Th2比例；通过CCR6抑制Th1细胞黏附^[9]	IL-17、IL-22、IFN-γ、TNF-α、CCR6^[9]	抑制促炎反应，增强抗炎作用，促进Treg细胞功能^[9]
Treg	TGF-β促进Fox3表达，增强Treg扩增^[11]；通过分泌可溶性因子增强Treg的抗炎作用^[11]	TGF-β、Foxp3、IL-10^[11]	增强免疫抑制和抗炎功能^[11]
CD8⁺ T细胞	直接接触抑制：通过BMSCs表面MICA/B与CD8⁺ T细胞NKG2D结合，下调NKG2D表达；分泌PGE2、IDO、TGF-β抑制活性^[10]	MICA/B、NKG2D、PGE2、IDO、TGF-β^[14]	抑制增殖和细胞毒性功能^[14]
B细胞	直接抑制B细胞增殖^[11]	未明确具体因子	抑制B细胞活化和抗体产生^[11]
DCs	抑制IL-1等细胞因子，减少促炎因子（IFN-γ、IL-12、TNF-α）分泌；促进抗炎因子IL-10分泌^[11,15]	IL-1、IFN-γ、IL-12、TNF-α、IL-10^[11,15]	降低DCs对T细胞的刺激能力，抑制炎症反应^[15]
巨噬细胞/小胶质细胞	促进M1型（促炎）向M2型（抗炎）转化^[16]；减少TNF-α、IL-1β分泌，增加IL-10、TGF-β分泌^[17]；通过调节AMPK/NF-κB通路抑制活化^[18]；分泌TSG-6抑制TLR2/MyD88/NF-κB通路^[18]	TNF-α、IL-1β、IL-10、TGF-β、AMPK/NF-κB、TSG-6^[16,17,18]	减轻神经炎症和中枢敏化^[18]，缓解疼痛，抑制过度免疫反应^[16]
NK细胞	抑制静息态NK细胞增殖和IFN-γ分泌（通过IDO、PGE2）^[19]；增强IL-12/IL-18预激活NK细胞的IFN-γ分泌（保留细胞毒性功能）^[19]；抑制IL-12/IL-18诱导的NK细胞活性^[19]	IDO、PGE₂、IL-12、IL-18、IFN-γ^[19,20]	双向调节：抑制静息态NK细胞功能，增强激活态NK细胞的抗病毒、肿瘤反应能力^[19]

免疫细胞类型	作用机制	涉及的因子/分子	功能效果
CD4⁺ T细胞	直接抑制增殖：抑制IL-2分泌及自然杀伤细胞活性；上调CD4⁺ CD25⁺ Treg细胞，抑制IFN-γ、IL-4等促炎因子^[13]；在炎症环境中促进IL-17产生^[11]	TGF-β、Foxp3、IL-2、IFN-γ、IL-4、IL-17^[9]	抑制T细胞活化^[10]和炎症反应^[9]，促进免疫耐受
Th1/Th2细胞	降低IL-17、IL-22、IFN-γ、TNF-α水平；抑制CD4⁺ T细胞向Th1分化；增加Th2细胞数量，改变Th1/Th2比例；通过CCR6抑制Th1细胞黏附^[9]	IL-17、IL-22、IFN-γ、TNF-α、CCR6^[9]	抑制促炎反应，增强抗炎作用，促进Treg细胞功能^[9]
Treg	TGF-β促进Fox3表达，增强Treg扩增^[11]；通过分泌可溶性因子增强Treg的抗炎作用^[11]	TGF-β、Foxp3、IL-10^[11]	增强免疫抑制和抗炎功能^[11]
CD8⁺ T细胞	直接接触抑制：通过BMSCs表面MICA/B与CD8⁺ T细胞NKG2D结合，下调NKG2D表达；分泌PGE2、IDO、TGF-β抑制活性^[10]	MICA/B、NKG2D、PGE2、IDO、TGF-β^[14]	抑制增殖和细胞毒性功能^[14]
B细胞	直接抑制B细胞增殖^[11]	未明确具体因子	抑制B细胞活化和抗体产生^[11]
DCs	抑制IL-1等细胞因子，减少促炎因子（IFN-γ、IL-12、TNF-α）分泌；促进抗炎因子IL-10分泌^[11,15]	IL-1、IFN-γ、IL-12、TNF-α、IL-10^[11,15]	降低DCs对T细胞的刺激能力，抑制炎症反应^[15]
巨噬细胞/小胶质细胞	促进M1型（促炎）向M2型（抗炎）转化^[16]；减少TNF-α、IL-1β分泌，增加IL-10、TGF-β分泌^[17]；通过调节AMPK/NF-κB通路抑制活化^[18]；分泌TSG-6抑制TLR2/MyD88/NF-κB通路^[18]	TNF-α、IL-1β、IL-10、TGF-β、AMPK/NF-κB、TSG-6^[16,17,18]	减轻神经炎症和中枢敏化^[18]，缓解疼痛，抑制过度免疫反应^[16]
NK细胞	抑制静息态NK细胞增殖和IFN-γ分泌（通过IDO、PGE2）^[19]；增强IL-12/IL-18预激活NK细胞的IFN-γ分泌（保留细胞毒性功能）^[19]；抑制IL-12/IL-18诱导的NK细胞活性^[19]	IDO、PGE₂、IL-12、IL-18、IFN-γ^[19,20]	双向调节：抑制静息态NK细胞功能，增强激活态NK细胞的抗病毒、肿瘤反应能力^[19]

免疫细胞类型	作用机制	涉及的因子/分子	功能效果
T细胞	抑制T细胞增殖与活化；诱导T细胞凋亡或失能	TGF-β、IL-10、PGE₂、IDO^[21,23]	减少T细胞过度活化，维持免疫耐受^[21]
Th1细胞	抑制Th1分化与功能^[24]；下调Th1相关转录因子^[25]	IDO（降解色氨酸）、TGF-β、STAT1/4抑制、T-bet下调^[24,25]	降低IFN-γ和TNF-α分泌，减轻Th1介导的炎症^[24,25]
Th2细胞	调节Th1/Th2平衡，可能增强Th2反应（微环境依赖性）^[26]	上调GATA-3^[33]，IL-4/IL-5/IL-13分泌增加（间接调控）	抑制Th1/Th17主导的炎症，但可能加重Th2相关过敏性疾病^[26]
Th17细胞	抑制Th17分化与IL-17A分泌；阻断IL-23信号通路	IL-10、TGF-β、IL-6/IL-23受体抑制、RORγt下调^[28,29]	减少Th17介导的自身免疫损伤^[28,29]
Treg	促进Treg扩增与功能活化^[30]；抑制Treg向Th17转化^[32]	IDO、TGF-β、IL-10、Foxp3上调^[34]	增强免疫抑制功能，缓解GVHD和自身免疫病^[31]
B细胞	抑制B细胞增殖与抗体产生；调节浆细胞分化^[35]	分泌IL-10和TGF-β^[35]	减少T细胞激活，促进免疫耐受^[35]
DCs	抑制树突细胞成熟与抗原呈递功能^[36]	分泌IL-10和PGE2，减少CD80和CD86表达^[36,37]	减轻炎症反应并维持免疫耐受^[37]
巨噬细胞/小胶质细胞	促炎M1型向抗炎M2型极化^[38,30]	分泌抗炎因子IL-10和TGF-β，激活巨噬细胞中的STAT3信号通路^[38]	减轻组织炎症，促进修复^[39]

免疫细胞类型	作用机制	涉及的因子/分子	功能效果
T细胞	抑制T细胞增殖与活化；诱导T细胞凋亡或失能	TGF-β、IL-10、PGE₂、IDO^[21,23]	减少T细胞过度活化，维持免疫耐受^[21]
Th1细胞	抑制Th1分化与功能^[24]；下调Th1相关转录因子^[25]	IDO（降解色氨酸）、TGF-β、STAT1/4抑制、T-bet下调^[24,25]	降低IFN-γ和TNF-α分泌，减轻Th1介导的炎症^[24,25]
Th2细胞	调节Th1/Th2平衡，可能增强Th2反应（微环境依赖性）^[26]	上调GATA-3^[33]，IL-4/IL-5/IL-13分泌增加（间接调控）	抑制Th1/Th17主导的炎症，但可能加重Th2相关过敏性疾病^[26]
Th17细胞	抑制Th17分化与IL-17A分泌；阻断IL-23信号通路	IL-10、TGF-β、IL-6/IL-23受体抑制、RORγt下调^[28,29]	减少Th17介导的自身免疫损伤^[28,29]
Treg	促进Treg扩增与功能活化^[30]；抑制Treg向Th17转化^[32]	IDO、TGF-β、IL-10、Foxp3上调^[34]	增强免疫抑制功能，缓解GVHD和自身免疫病^[31]
B细胞	抑制B细胞增殖与抗体产生；调节浆细胞分化^[35]	分泌IL-10和TGF-β^[35]	减少T细胞激活，促进免疫耐受^[35]
DCs	抑制树突细胞成熟与抗原呈递功能^[36]	分泌IL-10和PGE2，减少CD80和CD86表达^[36,37]	减轻炎症反应并维持免疫耐受^[37]
巨噬细胞/小胶质细胞	促炎M1型向抗炎M2型极化^[38,30]	分泌抗炎因子IL-10和TGF-β，激活巨噬细胞中的STAT3信号通路^[38]	减轻组织炎症，促进修复^[39]

免疫细胞类型	BMSCs作用特征	ADMSCs作用特征
T细胞	（1）抑制CD4⁺/CD8⁺ T增殖（非MHC限制性）；（2）通过TGF-β增强Treg功能^[51]	（1）优先抑制Th1/Th17分化；（2）通过IDO促进Treg扩增^[52]
巨噬细胞	促进M1→M2极化（PI3K/AKT通路激活）^[53]	间接调控M2极化（文献未明确通路）^[53]
NK细胞	双向调节：抑制静息态NK活性，增强IL-12/IL-18激活的NK功能	未明确直接作用^[54]
DCs	抑制IL-12分泌，降低T细胞活化能力^[55]	诱导耐受性DCs生成^[56]

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