Devireddy Ram V
Bioengineering Laboratory, Department of Mechanical Engineering, 2508 CEBA Bldg., Louisiana State University, Baton Rouge, LA 70803, USA.
Mol Reprod Dev. 2005 Mar;70(3):333-43. doi: 10.1002/mrd.20209.
This study presents a generic numerical model to simulate the coupled solute and solvent transport in human ovarian tissue sections during addition and removal of chemical additives or cryoprotective agents (CPA). The model accounts for the axial and radial diffusion of the solute (CPA) as well as axial convection of the CPA, and a variable vascular surface area (A) during the transport process. In addition, the model also accounts for the radial movement of the solvent (water) into and out of the vascular spaces. Osmotic responses of various cells within an human ovarian tissue section are predicted by the numerical model with three model parameters: permeability of the tissue cell membrane to water (L(p)), permeability of the tissue cell membrane to the solute or CPA (omega) and the diffusion coefficient of the solute or CPA in the vascular space (D). By fitting the model results with published experimental data on solute/water concentrations within an human ovarian tissue section, I was able to determine the permeability parameters of ovarian tissue cells in the presence of 1.5M solutions of each of the following: dimethyl sulphoxide (DMSO), propylene glycol (PROH), ethylene glycol (EG), and glycerol (GLY), at two temperatures (4 degrees C and 27 degrees C). Modeling Approach 1: Assuming a constant value of solute diffusivity (D = 1.0 x 10(-9) m(2)/sec), the best fit values of L(p) ranged from 0.35 x 10(-14) to 1.43 x 10(-14) m(3)/N-sec while omega ranged from 2.57 x 10(-14) to 70.5 x 10(-14) mol/N-sec. Based on these values of L(p) and omega, the solute reflection coefficient, sigma defined as sigma = 1-omega v(CPA)/L(P) ranged from 0.9961 to 0.9996. Modeling Approach 2: The relative values of omega and sigma from our initial modeling suggest that the embedded ovarian tissue cells are relatively impermeable to all the CPAs investigated (or omega approximately 0 and sigma approximately 1.0). Consequently the model was modified and used to predict the values of L(p) and D assuming omega = 0 and sigma = 1.0. The best fit values of L(p) ranged from 0.44 x 10(-14) to 1.2 x 10(-14) m(3)/N-sec while D ranged from 0.85 x 10(-9) to 2.08 x 10(-9) m(2)/sec. Modeling Approach 3: Finally, the best fit values of D from modeling approach 2 were incorporated into model 1 to re-predict the values of L(p) and omega. It is hoped that the ovarian tissue cell parameters reported here will help to optimize chemical loading and unloading procedures for whole ovarian tissue sections and consequently, tissue cryopreservation procedures.
本研究提出了一个通用数值模型，用于模拟在添加和去除化学添加剂或冷冻保护剂（CPA）过程中，人体卵巢组织切片内溶质与溶剂的耦合传输。该模型考虑了溶质（CPA）的轴向和径向扩散以及CPA的轴向对流，以及传输过程中可变的血管表面积（A）。此外，该模型还考虑了溶剂（水）进出血管空间的径向移动。通过具有三个模型参数的数值模型预测人体卵巢组织切片内各种细胞的渗透反应：组织细胞膜对水的渗透率（L(p)）、组织细胞膜对溶质或CPA的渗透率（ω）以及溶质或CPA在血管空间中的扩散系数（D）。通过将模型结果与已发表的关于人体卵巢组织切片内溶质/水浓度的实验数据进行拟合，我能够确定在以下每种物质的1.5M溶液存在下，卵巢组织细胞的渗透参数：二甲基亚砜（DMSO）、丙二醇（PROH）、乙二醇（EG）和甘油（GLY），在两个温度（4℃和27℃）下。建模方法1：假设溶质扩散率为恒定值（D = 1.0×10⁻⁹ m²/秒），L(p)的最佳拟合值范围为0.35×10⁻¹⁴至1.43×10⁻¹⁴ m³/N - 秒，而ω范围为2.57×10⁻¹⁴至70.5×10⁻¹⁴ mol/N - 秒。基于这些L(p)和ω值，溶质反射系数σ定义为σ = 1 - ωv(CPA)/L(P)，范围为0.9961至0.9996。建模方法2：我们初始建模中ω和σ的相对值表明，嵌入的卵巢组织细胞对所有研究的CPA相对不渗透（或ω约为0且σ约为1.0）。因此，对模型进行了修改，并用于预测假设ω = 0且σ = 1.0时的L(p)和D值。L(p)的最佳拟合值范围为0.44×10⁻¹⁴至1.2×10⁻¹⁴ m³/N - 秒，而D范围为0.85×10⁻⁹至2.08×10⁻⁹ m²/秒。建模方法3：最后，将建模方法2中D的最佳拟合值纳入模型1，以重新预测L(p)和ω的值。希望这里报告的卵巢组织细胞参数将有助于优化整个卵巢组织切片的化学加载和卸载程序，从而优化组织冷冻保存程序。
