骨髓来源细胞在慢性肾脏病大鼠模型原位工程化组织囊中的作用。
Contribution of bone marrow-derived cells to in situ engineered tissue capsules in a rat model of chronic kidney disease.
机构信息
Department of Internal Medicine, Leiden University Medical Center, the Netherlands; Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, the Netherlands.
Department of Bioengineering and Department of Medicine, University of California, Los Angeles, USA; Department of Bioengineering, University of California, Berkeley, USA.
出版信息
Biomaterials. 2019 Feb;194:47-56. doi: 10.1016/j.biomaterials.2018.12.014. Epub 2018 Dec 15.
Tissue engineered blood vessels (TEBVs) hold great promise for clinical use in patients with end stage renal disease (ESRD) requiring vascular access for hemodialysis. A promising way to make TEBVs is to exploit foreign body response (FBR) of polymeric rods used as templates. However, since the FBR predominantly involves bone-marrow (BM) derived cells and ESRD coincides with impaired function of BM, it is important to assess the generation of TEBVs in conditions of renal failure. To this end, we implanted polymer rods in the subcutis of rats after BM-transplantation with GFP-labeled BM cells in a model of chronic kidney disease (CKD). At 3 weeks after implantation, rods were encapsulated by tissue capsule (TC) composed of collagen, myofibroblasts and macrophages. On average, 13% of CD68 macrophages were GFP, indicating BM origin. Macrophage-to-myofibroblasts differentiation appeared to play an important role in TC formation as 26% of SMA/GFP myofibroblasts co-expressed the macrophage marker CD68. Three weeks after rod implantation, the cellular response changed towards tissue repair, characterized by 40% increase in CD68/CD163 repair associated macrophages and 95% increase in TGFβ and IL10 gene expression as compared to TCs harvested at 1 week. These results show that both BM derived and tissue resident cells, contribute to TC formation, whereas macrophages serve as precursors of myofibroblasts in mature TCs. Finally, the presence of CKD did not significantly alter the process of TC formation, which holds the potential to support our approach for future clinical use in ESRD patients.
组织工程血管（TEBV）在需要血管通路进行血液透析的终末期肾病（ESRD）患者的临床应用中具有巨大的应用前景。制造 TEBV 的一种有前途的方法是利用作为模板的聚合物棒的异物反应（FBR）。然而，由于 FBR 主要涉及骨髓（BM）来源的细胞，而 ESRD 与 BM 功能受损相吻合，因此评估在肾衰竭条件下 TEBV 的生成非常重要。为此，我们在慢性肾病（CKD）模型中用 GFP 标记的 BM 细胞进行 BM 移植后，将聚合物棒植入大鼠的皮下。在植入后 3 周，棒被由胶原蛋白、肌成纤维细胞和巨噬细胞组成的组织囊（TC）包裹。平均而言，13%的 CD68 巨噬细胞是 GFP，表明来源于 BM。巨噬细胞向肌成纤维细胞的分化似乎在 TC 形成中起着重要作用，因为 26%的 SMA/GFP 肌成纤维细胞共表达巨噬细胞标记物 CD68。在植入棒后 3 周，细胞反应向组织修复转变，与第 1 周收获的 TC 相比，CD68/CD163 修复相关巨噬细胞增加了 40%，TGFβ 和 IL10 基因表达增加了 95%。这些结果表明，BM 来源的细胞和组织驻留细胞都有助于 TC 的形成，而巨噬细胞在成熟 TC 中作为肌成纤维细胞的前体。最后，CKD 的存在并没有显著改变 TC 形成的过程，这为我们在 ESRD 患者的未来临床应用中提供了支持。
Zotero 插件