Novel Murine Xenograft Model for the Evaluation of Stem Cell Therapy for Profound Dysphagia
Novel Murine Xenograft Model for the Evaluation of Stem Cell Therapy for Profound Dysphagia
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DOI：
10.1002/lary.26666
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发表时间：
2017-10-01
期刊：
影响因子：
2.6
通讯作者：
Belafsky, Peter C.
中科院分区：
文献类型：
--
作者：
Kuhn, Maggie A.;Black, Amanda B.;Belafsky, Peter C.
目标/假设：吞咽困难很常见且代价高昂。治疗方法有限，需要创新疗法。舌头对于安全、有效的吞咽至关重要，也是再生治疗的天然目标。肌源性干细胞（MDSC）具有恢复动态功能的潜力，它们在受损舌头中的应用很有吸引力。我们检查了人类 MDSC 植入新型小鼠舌头模型的安全性和有效性。研究设计：动物研究。方法：将成年免疫缺陷小鼠随机分为手术组（半舌切除术）和非手术组。动物舌部注射人 MDSC 或盐水（对照）。对各组进行为期 12 周的随访。主要结果是通过体内成像系统 (IVIS) 测量的 MDSC 存活率。次要结果包括动物存活率和体重。使用 α 为 0.05 的 Mann-Whitney U 检验进行比较。结果：在 12 周时，半舌切除组和非手术组中，人类 MDSC 存活至终点，IVIS 分别显示 132% +/- 465% 和 15% +/- 11% 的生物发光。除一只动物（半舌切除术并注射盐水）外，所有动物均存活至研究终点。所有组的平均体重均较基线增加，其中在注射 MDSC 的半舌切除小鼠中观察到的变化最大（基线 24.5 +/- 6 3.9 g；delta 5.9 +/- 6 4.6 g），超过手术对照小鼠中观察到的体重增加（基线 24.9 g +/- 4.2 g，delta 2.7 g +/- 1.4 g）（P = .04）。结论：MDSC当注射到免疫缺陷的偏侧舌切除小鼠模型中时，3个月时表现出超过100%的存活率。注射 MDSC 的舌损伤动物在半舌切除术后表现出比对照动物更好的体重增加（P
Objectives/Hypothesis: Dysphagia is common and costly. Treatments are limited and innovative therapies are required. The tongue is essential for safe, effective swallowing and is a natural target for regenerative therapy. Muscle-derived stem cells (MDSCs) hold potential to restore dynamic function, and their application in the damaged tongue is appealing. We examined the safety and efficacy of human MDSC implantation into a novel mouse tongue model.Study Design: Animal study.Methods: Adult immune-deficient mice were randomized to surgical (hemiglossectomy) and nonsurgical groups. Animals underwent lingual injection of human MDSCs or saline (control). Groups were followed for 12 weeks. The primary outcome was MDSC survival measured by an in vivo imaging system (IVIS). Secondary outcomes included animal survival and weight. Comparisons were made using a Mann-Whitney U test with an alpha of .05.Results: Human MDSCs survived to the endpoint demonstrating 132% +/- 465% and 15% +/- 11% bioluminescence by IVIS at 12 weeks in hemiglossectomy and nonsurgical groups, respectively. All but one animal (hemiglossectomy with saline injection) survived to the study endpoint. Mean weight increased from baseline in all groups, with the greatest change observed in hemiglossectomy mice with MDSC injection (baseline 24.5 +/- 6 3.9 g; delta 5.9 +/- 6 4.6 g), exceeding the weight gain seen in surgical control mice (baseline 24.9 g +/- 4.2 g, delta 2.7 g +/- 1.4 g) (P = .04).Conclusions: MDSCs exhibited over 100% survival at 3 months when injected into an immune-deficient hemiglossectomy mouse model. Tongue-injured animals injected with MDSCs exhibited superior weight gain after hemiglossectomy than control animals (P