研究动态
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在小鼠模型中皮下异位自体移植后的脾脏再生。

Spleen regeneration after subcutaneous heterotopic autotransplantation in a mouse model.

发表日期:2023 Mar 29
作者: Andrey Elchaninov, Polina Vishnyakova, Anastasiya Lokhonina, Viktoria Kiseleva, Egor Menyailo, Maria Antonova, Aiaz Mamedov, Irina Arutyunyan, Galina Bolshakova, Dmitry Goldshtein, Xuhui Bao, Timur Fatkhudinov, Gennady Sukhikh
来源: Cellular & Molecular Immunology

摘要:

脾切除术可能导致严重的术后并发症,包括败血症和癌症。这个问题的一个可能解决方案是异位自体脾移植。脾自体移植可迅速恢复模型动物的常规脾组织结构。然而,这种再生的自体移植物在淋巴和造血能力方面的功能能力仍不确定。因此,本研究旨在监测小鼠脾自体移植中B和T淋巴细胞、单核巨噬细胞系统和巨核细胞生成的动力学。C57Bl雄性小鼠实施了皮下脾移植模型。利用B10-GFP供体对C57Bl接收者进行异位移植研究功能恢复的细胞来源。细胞组成动态通过免疫组织化学和流式细胞术进行研究。 mRNA和蛋白水平的调控基因表达通过实时PCR和Western blot进行评估。常规脾组织结构在移植后30天内恢复,与其他研究一致。而单核巨噬细胞系统、巨核细胞和B淋巴细胞的功能恢复速度最快,T细胞的功能恢复需要更长的时间。使用B10-GFP供体进行跨品系脾移植表明接收者衍生的细胞是功能恢复的来源。移植有脾内基质细胞或没有脾内基质细胞的支架均无法恢复特征性的脾组织结构。在小鼠模型中进行移植脾片的同种异体皮下移植术可在30天内恢复其结构,同时完全重建单核巨噬细胞系统、巨核细胞和B淋巴细胞群体。循环造血细胞为细胞组成恢复的主要来源。 © 2023. The Author(s).
Splenectomy may lead to severe postoperative complications, including sepsis and cancers. A possible solution to this problem is heterotopic autotransplantation of the spleen. Splenic autografts rapidly restore the regular splenic microanatomy in model animals. However, the functional competence of such regenerated autografts in terms of lympho- and hematopoietic capacity remains uncertain. Therefore, this study aimed to monitor the dynamics of B and T lymphocyte populations, the monocyte-macrophage system, and megakaryocytopoiesis in murine splenic autografts.The model of subcutaneous splenic engraftment was implemented in C57Bl male mice. Cell sources of functional recovery were studied using heterotopic transplantations from B10-GFP donors to C57Bl recipients. The cellular composition dynamics were studied by immunohistochemistry and flow cytometry. Expression of regulatory genes at mRNA and protein levels was assessed by real-time PCR and Western blot, respectively.Characteristic splenic architecture is restored within 30 days post-transplantation, consistent with other studies. The monocyte-macrophage system, megakaryocytes, and B lymphocytes show the highest rates, whereas the functional recovery of T cells takes longer. Cross-strain splenic engraftments using B10-GFP donors indicate the recipient-derived cell sources of the recovery. Transplantations of scaffolds populated with splenic stromal cells or without them afforded no restoration of the characteristic splenic architecture.Allogeneic subcutaneous transplantation of splenic fragments in a mouse model leads to their structural recovery within 30 days, with full reconstitution of the monocyte-macrophage, megakaryocyte and B lymphocyte populations. The circulating hematopoietic cells provide the likely source for the cell composition recovery.© 2023. The Author(s).