Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia Health System, Charlottesville, Va.
The Vascular and Cardiac Center for Adult Stem Cell Therapy, Indiana University School of Medicine, Indianapolis, Ind.
J Thorac Cardiovasc Surg. 2014 May;147(5):1668-1677.e5. doi: 10.1016/j.jtcvs.2013.09.041. Epub 2013 Nov 4.
Bone marrow-derived mesenchymal stem cells (MSCs) have shown therapeutic potential in acute lung injury. Recently, placenta-derived human mesenchymal stem cells (PMSCs) have shown similarities with bone marrow-derived MSCs in terms of regenerative capabilities and immunogenicity. This study investigates the hypothesis that treatment with PMSCs reduces the development of bronchiolitis obliterans in a murine heterotopic tracheal transplant model.
A murine heterotopic tracheal transplant model was used to study the continuum from acute to chronic rejection. In the treatment groups, PMSCs or PMSC-conditioned medium (PMSCCM) were injected either locally or intratracheally into the allograft. Phosphate-buffered saline (PBS) or blank medium was injected in the control groups. Tracheal luminal obliteration was assessed on sections stained with hematoxylin and eosin. Infiltration of inflammatory and immune cells and epithelial progenitor cells was assessed using immunohistochemistry and densitometric analysis.
Compared with injection of PBS, local injection of PMSCs significantly reduced luminal obliteration at 28 days after transplantation (P = .015). Intratracheal injection of PMSCs showed similar results to local injection of PMSCs compared with injection of PBS and blank medium (P = .022). Tracheas treated with PMSC/PMSCCM showed protection against the loss of epithelium on day 14, with an increase in P63+CK14+ epithelial progenitor cells and Foxp3+ regulatory T cells. In addition, injection of PMSCs and PMSCCM significantly reduced the number of neutrophils and CD3+ T cells on day 14.
This study demonstrates that treatment with PMSCs is protective against the development of bronchiolitis obliterans in an heterotopic tracheal transplant model. These results indicate that PMSCs could provide a novel therapeutic option to reduce chronic rejection after lung transplant.
骨髓间充质干细胞（MSCs）在急性肺损伤中显示出治疗潜力。最近，胎盘来源的人间充质干细胞（PMSCs）在再生能力和免疫原性方面与骨髓来源的 MSCs 具有相似性。本研究假设 PMSCs 治疗可减少小鼠异位气管移植模型中闭塞性细支气管炎的发展。
使用小鼠异位气管移植模型研究从急性到慢性排斥的连续过程。在治疗组中，将 PMSCs 或 PMSC 条件培养基（PMSCCM）局部或气管内注射到同种异体移植物中。在对照组中注射磷酸盐缓冲盐水（PBS）或空白培养基。用苏木精和伊红染色的切片评估气管腔闭塞情况。使用免疫组织化学和密度测定分析评估炎症和免疫细胞以及上皮祖细胞的浸润。
与注射 PBS 相比，局部注射 PMSCs 可显著减少移植后 28 天的管腔闭塞（P=0.015）。与注射 PBS 和空白培养基相比，气管内注射 PMSCs 与局部注射 PMSCs 具有相似的结果（P=0.022）。用 PMSC/PMSCCM 处理的气管在第 14 天显示出对上皮丧失的保护作用，上皮祖细胞 P63+CK14+增加，Foxp3+调节性 T 细胞增加。此外，注射 PMSCs 和 PMSCCM 可显著减少第 14 天中性粒细胞和 CD3+T 细胞的数量。
本研究表明，在异位气管移植模型中，PMSCs 治疗可预防闭塞性细支气管炎的发展。这些结果表明，PMSCs 可提供一种新的治疗选择，以减少肺移植后的慢性排斥反应。
