目的:间充质干细胞移植作为具有发展前景的脊髓损伤治疗方法之一,目前大多集中于小动物模型相关研究,大动物实验开展较少,并且对干细胞的种类选择与治疗效果仍存在争议。文章通过Meta分析间充质干细胞对大动物模型脊髓损伤相关指标的影...目的:间充质干细胞移植作为具有发展前景的脊髓损伤治疗方法之一,目前大多集中于小动物模型相关研究,大动物实验开展较少,并且对干细胞的种类选择与治疗效果仍存在争议。文章通过Meta分析间充质干细胞对大动物模型脊髓损伤相关指标的影响,评价其对脊髓损伤修复的作用。方法:计算机检索PubMed、Cochrane、OVID、Web of Science和中国知网,检索时限从建库起至2019年12月,收集关于间充质干细胞治疗大动物脊髓损伤的系列研究。由2位研究者按照纳入标准独立完成文献筛选、资料提取及方法学质量评价,采用Stata16.0进行Meta分析。结果:最终10篇文献纳入研究,Meta分析结果显示:①间充质干细胞可显著改善脊髓损伤后运动功能[I2=97.73%,MD=3.94,95%CI(2.15,5.72),P<0.01],并根据细胞来源、观察时间、移植时机、移植方式和移植类型分不同进行亚组分析:骨髓间充质干细胞组、非骨髓间充质干细胞组、短时间观察组(<2个月)、长时间观察组(≥2个月)、急性期移植组、非急性期移植组、单纯细胞移植组、异种移植组的运动评分明显高于对照组(P<0.01);而支架复合移植组运动评分相较对照组,差异无显著性意义(P>0.05);②间充质干细胞治疗组的损伤面积明显小于对照组[I2=98.05%,MD=-1.00,95%CI(-1.95,-0.04),P=0.04];③间充质干细胞治疗组与对照组之间胶质纤维酸性蛋白相对表达量差异无显著性意义[I2=99.48%,MD=80.61,95%CI(-27.48,188.70),P=0.14]。结论:间充质干细胞移植治疗对大动物脊髓损伤的运动功能和损伤修复有明显改善作用,且安全性较高。受纳入文献质量的限制,以上结论需更高质量、更大样本的随机对照实验加以验证。展开更多
Ex vivo lung perfusion(EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventila...Ex vivo lung perfusion(EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time,EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result,this technique provides uniqueadvantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript,we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine.展开更多
The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore p...The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore potential therapeutic interventions.Although promising therapeutics have been identified using these animal models,with most undergoing significant testing in rodent models,the vast majority of these interventions have failed in human clinical trials.This failure of preclinical translation highlights the critical need for better therapeutic assessment in more clinically relevant ischemic stroke animal models.Large animal models such as non-human primates,sheep,pigs,and dogs are likely more predictive of human responses and outcomes due to brain anatomy and physiology that are more similar to humans-potentially making large animal testing a key step in the stroke therapy translational pipeline.The objective of this review is to highlight key characteristics that potentially make these gyrencephalic,large animal ischemic stroke models more predictive by comparing pathophysiological responses,tissue-level changes,and model limitations.展开更多
Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the...Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.展开更多
文摘目的:间充质干细胞移植作为具有发展前景的脊髓损伤治疗方法之一,目前大多集中于小动物模型相关研究,大动物实验开展较少,并且对干细胞的种类选择与治疗效果仍存在争议。文章通过Meta分析间充质干细胞对大动物模型脊髓损伤相关指标的影响,评价其对脊髓损伤修复的作用。方法:计算机检索PubMed、Cochrane、OVID、Web of Science和中国知网,检索时限从建库起至2019年12月,收集关于间充质干细胞治疗大动物脊髓损伤的系列研究。由2位研究者按照纳入标准独立完成文献筛选、资料提取及方法学质量评价,采用Stata16.0进行Meta分析。结果:最终10篇文献纳入研究,Meta分析结果显示:①间充质干细胞可显著改善脊髓损伤后运动功能[I2=97.73%,MD=3.94,95%CI(2.15,5.72),P<0.01],并根据细胞来源、观察时间、移植时机、移植方式和移植类型分不同进行亚组分析:骨髓间充质干细胞组、非骨髓间充质干细胞组、短时间观察组(<2个月)、长时间观察组(≥2个月)、急性期移植组、非急性期移植组、单纯细胞移植组、异种移植组的运动评分明显高于对照组(P<0.01);而支架复合移植组运动评分相较对照组,差异无显著性意义(P>0.05);②间充质干细胞治疗组的损伤面积明显小于对照组[I2=98.05%,MD=-1.00,95%CI(-1.95,-0.04),P=0.04];③间充质干细胞治疗组与对照组之间胶质纤维酸性蛋白相对表达量差异无显著性意义[I2=99.48%,MD=80.61,95%CI(-27.48,188.70),P=0.14]。结论:间充质干细胞移植治疗对大动物脊髓损伤的运动功能和损伤修复有明显改善作用,且安全性较高。受纳入文献质量的限制,以上结论需更高质量、更大样本的随机对照实验加以验证。
文摘Ex vivo lung perfusion(EVLP) is a powerful experimental model for isolated lung research. EVLP allows for the lungs to be manipulated and characterized in an external environment so that the effect of specific ventilation/perfusion variables can be studied independent of other confounding physiologic contributions. At the same time,EVLP allows for normal organ level function and real-time monitoring of pulmonary physiology and mechanics. As a result,this technique provides uniqueadvantages over in vivo and in vitro models. Small and large animal models of EVLP have been developed and each of these models has their strengths and weaknesses. In this manuscript,we provide insight into the relative strengths of each model and describe how the development of advanced EVLP protocols is leading to a novel experimental platform that can be used to answer critical questions in pulmonary physiology and transplant medicine.
基金supported by the National Institutes of Health,National Institute of Neurological Disorders and Stroke,No.R01NS093314
文摘The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore potential therapeutic interventions.Although promising therapeutics have been identified using these animal models,with most undergoing significant testing in rodent models,the vast majority of these interventions have failed in human clinical trials.This failure of preclinical translation highlights the critical need for better therapeutic assessment in more clinically relevant ischemic stroke animal models.Large animal models such as non-human primates,sheep,pigs,and dogs are likely more predictive of human responses and outcomes due to brain anatomy and physiology that are more similar to humans-potentially making large animal testing a key step in the stroke therapy translational pipeline.The objective of this review is to highlight key characteristics that potentially make these gyrencephalic,large animal ischemic stroke models more predictive by comparing pathophysiological responses,tissue-level changes,and model limitations.
文摘Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.
