Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering.
Sex and Tamoxifen confound murine experimental studies in cardiovascular tissue engineering.
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DOI：
10.1038/s41598-021-87006-3
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发表时间：
2021-04-13
影响因子：
4.6
通讯作者：
Breuer CK
中科院分区：
文献类型：
--
作者：
Blum KM;Roby LC;Zbinden JC;Chang YC;Mirhaidari GJM;Reinhardt JW;Yi T;Barker JC;Breuer CK
组织工程血管移植物有望从可生物降解的支架中产生功能性血管。由于调控这一过程的精确机制仍在研究中，诱导型遗传小鼠模型是一种重要且广泛使用的研究工具。然而，在这里，我们描述的重要性，挑战的基线假设，他莫昔芬是惰性的，当用作小分子诱导剂的背景下，心血管组织工程。在C57 BL/6小鼠中采用标准的下腔静脉血管间置移植物模型，我们发现对照组和他莫昔芬治疗组动物之间的免疫反应存在差异，包括闭塞率、巨噬细胞浸润和表型、异物巨细胞发育的程度和胶原沉积。此外，在未给药雄性和雌性之间观察到差异。我们的研究结果表明，心血管组织工程中常用材料的宿主反应是性别特异性的，并受到他莫昔芬暴露的严重影响，需要仔细选择模型和解释结果。
Tissue engineered vascular grafts hold promise for the creation of functional blood vessels from biodegradable scaffolds. Because the precise mechanisms regulating this process are still under investigation, inducible genetic mouse models are an important and widely used research tool. However, here we describe the importance of challenging the baseline assumption that tamoxifen is inert when used as a small molecule inducer in the context of cardiovascular tissue engineering. Employing a standard inferior vena cava vascular interposition graft model in C57BL/6 mice, we discovered differences in the immunologic response between control and tamoxifen-treated animals, including occlusion rate, macrophage infiltration and phenotype, the extent of foreign body giant cell development, and collagen deposition. Further, differences were noted between untreated males and females. Our findings demonstrate that the host-response to materials commonly used in cardiovascular tissue engineering is sex-specific and critically impacted by exposure to tamoxifen, necessitating careful model selection and interpretation of results.
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影响因子：
20.1
作者：
Doetschman T;Azhar M
通讯作者：
Azhar M
DOI：
10.1093/jnci/90.19.1461
发表时间：
1998-10-07
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Decensi, A;Bonanni, BD;Veronesi, U
通讯作者：
Veronesi, U
DOI：
10.1073/pnas.1300290110
发表时间：
2013-06-04
影响因子：
11.1
作者：
Godwin, James W.;Pinto, Alexander R.;Rosenthal, Nadia A.
通讯作者：
Rosenthal, Nadia A.
影响因子：
13.6
作者：
Delle, Humberto;Rocha, Jose Roberto C.;Noronha, Irene L.
通讯作者：
Noronha, Irene L.
影响因子：
4.1
作者：
Duijvelshoff, Renee;di Luca, Andrea;Bouten, Carlijn V. C.
通讯作者：
Bouten, Carlijn V. C.