CRYOBIOPHYSICAL CHARACTERISTICS OF SPHEROIDS

描述：球体的冻结特性是独一无二的 与组成聚集体的孤立细胞的情况不同。这个 低温性能的表征将是至关重要的 球体冷冻保存方案的研究进展。两种不同的 感兴趣的实验系统将被调查：由以下物质制成的球体 肝细胞和前列腺肿瘤细胞。之所以选择这两个系统，是因为 它们的临床相关性。肝细胞球体目前处于 用于生物人工肝的研究。前列腺球体有 以前被用来测试不同治疗的有效性 前列腺癌的治疗方法。 本次调查的具体目的是：(1)确定基本情况 形成聚集体的分离细胞的低温生物物理参数；(2) 确定球体的基本低温生物物理参数 冰冻；(3)开发单室和多室模型 水在椭球体内的传输；(4)使用 不同热力和化学条件下的可控率冷冻机 确定球体内活细胞的空间分布和 功能可行性；(5)开发提高功能可行性的方法 肝细胞球体与超低温保存过程中肿瘤球体的损伤。 这项调查的结果将为 超低温保存的冷冻方案及其发展 冷冻手术方案。肝细胞球体冷冻保存成功 将促进基于球体的肝支持的临床应用 系统。破坏机制的确定和加强的方法 损害将促进冷冻外科方案的发展 前列腺癌的治疗。

DESCRIPTION: The freezing characteristics of spheroids are unique and differ from that of the isolated cells which comprise the aggregate. The characterization of the low temperature properties will be essential to the development of cryopreservation protocols for spheroids. Two different experimental systems of interest will be investigated: spheroids made from hepatocytes and prostate tumor cells. These two systems were chosen because of their clinical relevance. Hepatocyte spheroids are presently under investigation for use in a Bio-Artificial Liver. Prostate spheroids have been used previously to test the effectiveness of different treatment modalities on prostate cancer. The specific aims of this investigation are: (1) to determine the basic cryobiophysical parameters of isolated cells which form the aggregates; (2) to determine the basic cryobiophysical parameters for the spheroids during freezing; (3) to develop single as well as multicompartment models for the water transport within a spheroid; (4) to freeze spheroids using a controlled rate freezer under different thermal and chemical conditions and determine the spatial distribution of viable cells within the spheroid and functional viability; (5) to develop methods of enhancing viability for hepatocyte spheroids and damage for tumor spheroids during cryopreservation. The results of this investigation will provide a rational basis for the development of freezing protocols for cryopreservation as well as cryosurgical protocols. Successful cryopreservation of hepatocyte spheroids will facilitate the clinical applications of spheroid-based liver support systems. Determination of the damage mechanisms and methods to enhance damage will facilitate development of cryosurgical protocols for the treatment of prostate cancer.