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人类羊上皮干细胞是预防急性移植与宿主疾病的细胞治疗候选者

Peng-Jie Yang¹, Xiang-Yu Zhao², Yao-Hui Kou^1,3

¹MOE Laboratory of Biosystems Homeostasis & Protection of College of Life Sciences, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province of Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310058, China.

Acta pharmacologica Sinica

|May 27, 2024

概括

人类羊上皮干细胞 (hAESCs) 在干细胞移植后对移植与宿主疾病 (GVHD) 的治疗有前途. 这些细胞缓解GVHD症状,并保持移植与白血病的效应,为传统免疫抑制剂提供更安全的替代品.

科学领域:

免疫学免疫学免疫学
细胞疗法细胞疗法
移植医学移植医学

背景情况:

移植与宿主疾病 (GVHD) 是异构造造血干细胞移植 (allo-HSCT) 的一个主要并发症.
目前用于GVHD的免疫抑制治疗具有显著的副作用.
人类羊上皮干细胞 (hAESCs) 具有免疫调节性质,使它们成为潜在的治疗候选者.

研究的目的:

在人性化的小鼠模型中评估cGMP级aHESCs在预防和治疗急性GVHD (aGVHD) 的治疗效果.
阐明GVHD中HAESCs的免疫调节机制.
评估HaaESCs对移植与白血病 (GVL) 效应的影响.

主要方法:

通过注射人类外周血液单核细胞 (huPBMCs) 来建立aGVHD的人性化小鼠模型.
对aGVHD.的预防 (第1天) 或治疗 (第7天) 进行aHESC的管理.
分析疾病表型,生存率,病理性损伤,CD4+T细胞极化 (Th1,Th17,Treg),细胞因子概况和GVL效应.

主要成果:

hAESC输液显著缓解了aGVHD症状,改善了生存率,并减少了器官损伤.
hAESCs促进了Treg细胞的扩张,同时抑制了Th1和Th17子集.
hAESCs分泌TGFβ和PGE2,调解Treg升高和Th1/Th17抑制,并保留了GVL效应.
在HSCT患者的初步数据表明,抗GVHD作用没有安全问题.

结论:

hAESC输液是一种有前途的治疗策略,用于管理HSCT后的GVHD.
hAESCs调节T细胞反应和细胞因子档案以控制GVHD.
这种方法提供了一个潜在的好处,即保留GVL效应,与传统的免疫抑制剂不同.

关键词:

接种与宿主病的疾病.造血干细胞移植造血干细胞移植人类胚胎上皮干细胞免疫调节免疫调节免疫调节

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