Stem Cell Research & Therapy:干细胞与新冠肺炎:人类羊膜细胞是治疗SARS-CoV-2病毒的新希望吗?

2021-03-16 MedSci原创 MedSci原创

羊膜细胞治疗新冠肺炎将是一种很有前途的治疗方法。它们可能会起到双重作用,不仅是通过防止细胞因子风暴,也是通过修复和替换受损的组织。这些特点使人羊膜干细胞成为开发新冠肺炎新的成功方案和治疗方法的候选细

 

由SARS-CoV-2病毒引起的一种新型冠状病毒呼吸道疾病(新冠肺炎)震惊了全世界,造成了社会、经济和健康问题。新冠肺炎在重症患者中引发肺部感染,并引发多种促炎细胞因子风暴。如果没有有效和安全的治疗,新冠肺炎已经导致数以千计的人死亡,成为一种流行病。干细胞已被建议作为肺部相关疾病的一种治疗方法。特别值得一提的是,间充质干细胞(MSCs)已经在一些新冠肺炎患者的临床试验中得到了成功的测试。令人鼓舞的结果使骨髓间充质干细胞成为新冠肺炎的一种可能的细胞疗法。足月人胎盘羊膜是一种有价值的干细胞来源,包括人羊膜上皮细胞(HAECs)和人间充质基质细胞(HAMSCs)。Stem Cell Research & Therapy杂志文章回顾和讨论了新冠肺炎的一般特征,目前对骨髓间充质干细胞的临床试验,以及使用人羊膜干细胞进行治疗的可能选择。

SARS-CoV-2的结构和细胞进入。A冠状病毒(CoVS)结构复杂,包括三种主要结构蛋白:刺状糖蛋白(S)、跨膜糖蛋白(M)和核衣壳蛋白(N)。在病毒包膜中发现了糖蛋白S。包膜蛋白(E)是一种存在于结构区的次要跨膜蛋白。冠状病毒基因组由30kb大小的正向单链RNA组成。B作为一种冠状病毒,SARS-CoV-2使用S糖蛋白来促进进入宿主细胞。这种病毒主要针对表达血管紧张素转换酶2受体(ACE2)的呼吸道上皮细胞。S蛋白与ACE2结合,允许病毒进入宿主细胞胞浆。蛋白酶,如TMPRRS2、组织蛋白酶或呋喃,通过S蛋白的裂解帮助病毒和细胞膜融合。病毒进入后,病毒基因组RNA中的复制酶基因被翻译。然后,合成病毒RNA并组装复制酶复合物。在内质网中发生结构糖蛋白S、M和E的翻译,所有翻译的蛋白都相互作用以组装冠状病毒。一旦病毒粒子形成,它们以小泡的形式被运送到宿主细胞表面,然后通过胞吐作用释放出来。

羊膜干细胞治疗新冠肺炎的前景展望。足月从人胎盘羊膜分离的干细胞包括hAECs和hAMSCs。HAMSCs和hAECs具有免疫调节、抗炎和再生特性。这些特点使羊膜干细胞成为成功治疗新冠肺炎的候选细胞。羊膜干细胞治疗可以减轻SARS-CoV-2病毒引起的急性呼吸窘迫综合征(ARDS)的细胞因子风暴。羊膜细胞可以调节T、B淋巴细胞、NK细胞、DC、中性粒细胞和巨噬细胞等免疫细胞的增殖、功能和迁移。因此,hAECs和hAMSCs可刺激调节性免疫细胞减少肺部炎症微环境。此外,羊膜细胞还可降低促炎细胞因子(TNF-α、干扰素-γ、IL-6、单核细胞趋化蛋白-1),增加可溶性抗炎因子(IL-10、IL-1、β、PGE_2、MIF、VEGF、IDO)的释放。另外,羊膜细胞可通过抑制转化生长因子β在肺损伤灶处发挥抗纤维化作用。总之,人羊膜干细胞治疗可以防止新冠肺炎患者的多器官衰竭进展。

有趣的是,羊膜细胞具有免疫调节、再生和抗炎等特性。此外,hAECs和hAMSCs已经用于临床前研究和治疗呼吸系统疾病的临床试验。在活体肺损伤模型中,它们减轻了炎症反应,恢复了肺组织结构。Rodrigo N. Riedel回顾关于干细胞用于新冠肺炎治疗的现有数据,包括正在进行的临床试验。还考虑了正在应用的非细胞疗法。最后,讨论了人类羊膜细胞在患有免疫性/炎症性肺部疾病的患者中的应用,并假设它们可能作为对抗新冠肺炎的成功治疗方法。

hAMSCs和hAECs的旁分泌活性可以抑制SARS-CoV-2病毒引起的ARDS免疫系统的恶化。羊膜细胞可以减少肺损伤部位促炎细胞因子的分泌,并减弱中性粒细胞、巨噬细胞和淋巴细胞的迁移。清除这些炎性介质可能会抑制细胞因子风暴,防止多器官衰竭的进展。此外,hAMSCs和hAECs可以调节免疫细胞的增殖和激活,诱导向抗炎表型的转变。此外,羊膜细胞不仅可以促进促炎环境的调节,而且可以替代病变细胞。此外,人羊膜细胞可以通过降低转化生长因子-β等因子来对抗纤维化。

值得注意的是,HLA-G在hAMSCs和hAECs中的表达将允许更好的移植耐受性,因为这种分子可以抑制NK细胞毒性,调节T细胞和B细胞的增殖和活性。值得一提的是,羊膜细胞的扩增能力有限,它们可能会在传代过程中失去有益的能力。重要的是,新方案的开发将提高临床使用的羊水细胞的数量和质量。

综上所述,由于羊膜细胞的分化能力和毋庸置疑的免疫调节特性,羊膜细胞治疗新冠肺炎将是一种很有前途的治疗方法。它们可能会起到双重作用,不仅是通过防止细胞因子风暴,也是通过修复和替换受损的组织。这些特点使人羊膜干细胞成为开发新冠肺炎新的成功方案和治疗方法的候选细胞。来自人类胎盘羊膜的干细胞应该被考虑用于治疗这种类型的肺部感染以及广泛的疾病。

原文出处

Riedel Rodrigo N,Pérez-Pérez Antonio,Sánchez-Margalet Víctor et al. Stem cells and COVID-19: are the human amniotic cells a new hope for therapies against the SARS-CoV-2 virus?[J] .Stem Cell Res Ther, 2021, 12: 155.

 

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topicName=ERA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e36234488643, createdName=124988c7m106暂无昵称, createdTime=Fri Dec 17 12:35:59 CST 2021, time=2021-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970029, encodeId=995b19e0029af, content=<a href='/topic/show?id=ec345834075' target=_blank style='color:#2F92EE;'>#新希望#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58340, encryptionId=ec345834075, topicName=新希望)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25d7319, createdName=珙桐, createdTime=Tue Oct 12 00:35:59 CST 2021, time=2021-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025547, encodeId=7482102554eb1, content=干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Fri Mar 19 23:35:59 CST 2021, time=2021-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1321261, encodeId=2b95132126120, content=<a href='/topic/show?id=ac0d159007f' target=_blank style='color:#2F92EE;'>#SARS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15900, encryptionId=ac0d159007f, topicName=SARS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8306486, createdName=小刀医生, createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482321, encodeId=5aa814823215d, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=)]
    2021-11-12 湘雅科教

    已拜读,受益匪浅。

    0

  4. 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  5. 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topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Fri Mar 19 23:35:59 CST 2021, time=2021-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1321261, encodeId=2b95132126120, content=<a href='/topic/show?id=ac0d159007f' target=_blank style='color:#2F92EE;'>#SARS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15900, encryptionId=ac0d159007f, topicName=SARS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8306486, createdName=小刀医生, createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482321, encodeId=5aa814823215d, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, 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    2021-07-08 维他命
  6. 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  7. 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topicName=ERA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e36234488643, createdName=124988c7m106暂无昵称, createdTime=Fri Dec 17 12:35:59 CST 2021, time=2021-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970029, encodeId=995b19e0029af, content=<a href='/topic/show?id=ec345834075' target=_blank style='color:#2F92EE;'>#新希望#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58340, encryptionId=ec345834075, topicName=新希望)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25d7319, createdName=珙桐, createdTime=Tue Oct 12 00:35:59 CST 2021, time=2021-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025547, encodeId=7482102554eb1, content=干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Fri Mar 19 23:35:59 CST 2021, time=2021-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1321261, encodeId=2b95132126120, content=<a href='/topic/show?id=ac0d159007f' target=_blank style='color:#2F92EE;'>#SARS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15900, encryptionId=ac0d159007f, topicName=SARS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8306486, createdName=小刀医生, createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482321, encodeId=5aa814823215d, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=)]
    2021-10-12 珙桐
  8. 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topicName=ERA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e36234488643, createdName=124988c7m106暂无昵称, createdTime=Fri Dec 17 12:35:59 CST 2021, time=2021-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970029, encodeId=995b19e0029af, content=<a href='/topic/show?id=ec345834075' target=_blank style='color:#2F92EE;'>#新希望#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58340, encryptionId=ec345834075, topicName=新希望)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25d7319, createdName=珙桐, createdTime=Tue Oct 12 00:35:59 CST 2021, time=2021-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025547, encodeId=7482102554eb1, content=干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=独孤立克, createdTime=Fri Mar 19 23:35:59 CST 2021, time=2021-03-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1321261, encodeId=2b95132126120, content=<a href='/topic/show?id=ac0d159007f' target=_blank style='color:#2F92EE;'>#SARS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15900, encryptionId=ac0d159007f, topicName=SARS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8306486, createdName=小刀医生, createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1482321, encodeId=5aa814823215d, content=<a href='/topic/show?id=8cc416e78f3' target=_blank style='color:#2F92EE;'>#STEM#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=)]
    2021-03-19 独孤立克

    干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦

    0

  9. 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topicName=ERA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e36234488643, createdName=124988c7m106暂无昵称, createdTime=Fri Dec 17 12:35:59 CST 2021, time=2021-12-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1970029, encodeId=995b19e0029af, content=<a href='/topic/show?id=ec345834075' target=_blank style='color:#2F92EE;'>#新希望#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=58340, encryptionId=ec345834075, topicName=新希望)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=25d7319, createdName=珙桐, createdTime=Tue Oct 12 00:35:59 CST 2021, time=2021-10-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1025547, encodeId=7482102554eb1, content=干细胞是热点,但是进入临床仍然需要时间和临床疗效验证哦, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, 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replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=16778, encryptionId=8cc416e78f3, topicName=STEM)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d1067833268, createdName=12498bb3m92(暂无昵称), createdTime=Thu Mar 18 14:35:59 CST 2021, time=2021-03-18, status=1, ipAttribution=)]
    2021-03-18 小刀医生
  10. 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