Office of Therapeutic Product, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD, 20993, USA.
Department of Mechanical Engineering, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea.
Adv Biol (Weinh). 2024 Aug;8(8):e2300094. doi: 10.1002/adbi.202300094. Epub 2023 Jul 6.
Mesenchymal stromal cells (MSCs) continue to be proposed for clinical investigation to treat myriad diseases given their purported potential to stimulate endogenous regenerative processes, such as angiogenesis. However, MSC functional heterogeneity has hindered clinical success and still poses a substantial manufacturing challenge from a product quality control perspective. Here, a quantitative bioassay based on an enhanced-throughput is described, microphysiological system (MPS) to measure the specific bioactivity of MSCs to stimulate angiogenesis as a potential measure of MSC potency. Using this novel bioassay, MSCs derived from multiple donors at different passages are co-cultured with human umbilical vein endothelial cells and exhibit significant heterogeneity in angiogenic potency between donors and cell passage. Depending on donor source and cellular passage number, MSCs varied in their ability to stimulate tip cell dominant or stalk cell dominant phenotypes in angiogenic sprout morphology which correlated with expression levels of hepatocyte growth factor (HGF). These findings suggest that MSC angiogenic bioactivity may be considered as a possible potency attribute in MSC quality control strategies. Development of a reliable and functionally relevant potency assay for measuring clinically relevant potency attributes of MSCs will help to improve consistency in quality and thereby, accelerate clinical development of these cell-based products.
间充质基质细胞（MSCs）因其据称具有刺激内源性再生过程（如血管生成）的潜力，因此继续被提议用于临床研究以治疗多种疾病。然而，MSC 功能异质性阻碍了临床成功，并且从产品质量控制的角度来看，仍然构成了实质性的制造挑战。在这里，描述了一种基于高通量增强的定量生物测定，微生理系统（MPS），用于测量刺激血管生成的 MSC 的特定生物活性，作为 MSC 效力的潜在测量。使用这种新型生物测定，来自不同传代数的多个供体的 MSC 与人脐静脉内皮细胞共培养，并且在供体和细胞传代数之间在血管生成效力方面表现出显著的异质性。根据供体来源和细胞传代数，MSC 在刺激血管生成芽形态中的尖端细胞优势或茎细胞优势表型的能力上存在差异，这与肝细胞生长因子（HGF）的表达水平相关。这些发现表明，MSC 血管生成生物活性可以被认为是 MSC 质量控制策略中可能的效力属性。开发一种可靠且功能相关的效力测定法，用于测量 MSC 的临床相关效力属性，将有助于提高质量的一致性，从而加速这些基于细胞的产品的临床开发。
