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脐带血 CD34 干细胞和牙髓间充质干细胞移植在预防和治疗早期/急性曼氏血吸虫肝肉芽肿中的作用:一种新方法。

Prophylactic versus therapeutic role of the transplanted CD34 Umbilical Cord Blood Stem Cells and Wharton Jelly Mesenchymal Stem Cells in early / acute hepatic S. mansoni granulomas reversal in mice; a novel approach.

机构信息

Department of Pathology, Theodor Bilharz Research Institute (TBRI), Imbaba, Giza, Egypt.

Departments of Parasitology, Immunology & Drug Evaluation, Theodor Bilharz Research Institute (TBRI), Imbaba, Giza, Egypt.

出版信息

Exp Parasitol. 2020 Oct;217:107938. doi: 10.1016/j.exppara.2020.107938. Epub 2020 Aug 5.

Abstract

PURPOSE

Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34 Umbilical Cord Blood Stem Cells (CD34UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice.

METHODS

Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed.

RESULTS

Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34UCBSCs and WJMSCs) & similarly the post-infection CD34UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis.

CONCLUSION

CD34UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.

摘要

目的

吡喹酮(PZQ)是传统的抗血吸虫药物。然而,目前尚无批准的抗血吸虫预防性药物或 100%可治愈的疗法,也没有关于人脐血 CD34 造血干细胞(CD34UCBSCs)或牙髓间质干细胞(WJMSCs)在预防和/或完全消除急性 S.mansoni 肝肉芽肿中的应用的报告数据。我们旨在研究人 CD34UCBSCs 和 WJMSCs 在预防和治疗感染前和感染后小鼠急性肝血吸虫肉芽肿中的可能作用。

方法

将 70 只小鼠分为 7 组(每组 10 只):正常组、感染 S.mansoni 组、感染后 PZQ 治疗组、感染前和感染后 CD34UCBSCs 组、感染前和感染后 WJMSCs 组。进行血清学、寄生虫学、组织病理学评估,使用 OCT4 和 TGFB 免疫组织化学,并对肝肉芽肿中 TGFB 染色纤维化进行定量图像分析评估。

结果

组织病理学上,令人惊讶和显著的是,预防性感染前干细胞(CD34UCBSCs 和 WJMSCs)治疗和类似地感染后 CD34UCBSCs 治疗,显示出整个肉芽肿的消除/逆转,没有纤维化。此外,感染后 PZQ 治疗组的肉芽肿数量明显少于感染后 WJMSCs 治疗组。然而,感染后 WJMSCs 显示出非显著性较少的 TGFB 染色纤维化。

结论

CD34UCBSCs 在预防和完全治愈急性 S.mansoni 肝肉芽肿方面,比 WJMSCs 和 PZQ 发挥了最佳的预防和治疗作用。相比之下,只有感染前 WJMSCs 显示出类似的预防(预防)作用。相反,感染后 WJMSCs 是最差的(不完全逆转的肉芽肿)。在这方面,感染后 PZQ 在治疗上总体上优于 WJMSCs。因此,当涉及到 WJMSCs 的应用时,WJMSCs 作为感染前的预防和预防工具更好,而不是感染后的治疗工具。需要进一步的研究。

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