Bzinkowska Aleksandra, Sarnowska Anna
Translational Platform for Regenerative Medicine, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.
Stem Cells Cloning. 2024 Oct 5;17:21-32. doi: 10.2147/SCCAA.S471118. eCollection 2024.
Mesenchymal stem/stromal cells (MSCs)-based products have unique characteristics compared to other drugs because of their inherently variable effects depending on culture conditions and microenvironment. In some cases, cells can be produced individually, one batch at a time, for personalized therapy. Therefore, it is very important to optimize both culture conditions and medium composition under Good Manufacturing Practice (GMP) standards. MSCs properties have been exploited as potential cell therapies in regenerative medicine. The main mechanism of their protective and regenerative effect is based on their secretory activity. Simultaneously, their secretome is highly variable and sensitive to any change in environmental conditions. Depending on the type of damage and the target application, it is desirable to enhance the secretion of therapeutic factors. Changes in the modulation of environmental conditions can affect survival, migration ability, and both proliferative and clonogenic potentials.
This study cultured Wharton's jelly-derived MSCs (WJ-MSCs) in media with varying concentrations of human platelet lysate (hPL). Two groups were created: one with low hPL concentration and another with a high hPL concentration. The effects of these different hPL concentrations were analyzed by assessing mesenchymal phenotype retention, secretory activity, clonogenic potential, proliferation, and migration capabilities. Additionally, the secretion levels of key therapeutic factors, such as Hepatocyte Growth Factor (HGF), Brain-Derived Neurotrophic Factor (BDNF), and Chemokine Ligand 2 (CCL-2), were measured.
WJ-MSCs maintained their mesenchymal phenotype regardless of hPL concentration. However, a higher concentration of hPL promoted cell clonogenic potential, proliferation, migration, and increased secretion of therapeutic factors.
Adjusting the hPL concentration in the culture medium modulates the response of WJ MSCs and enhances their therapeutic potential. Higher hPL concentration promotes increased secretory activity and improves the regenerative capacity of WJ-MSCs, suggesting a promising strategy to optimize MSC-based therapies.
与其他药物相比，基于间充质干/基质细胞（MSCs）的产品具有独特的特性，因为其作用本质上会因培养条件和微环境而有所不同。在某些情况下，细胞可以逐个批次生产，用于个性化治疗。因此，按照药品生产质量管理规范（GMP）标准优化培养条件和培养基成分非常重要。MSCs的特性已被用作再生医学中潜在的细胞疗法。其保护和再生作用的主要机制基于其分泌活性。同时，它们的分泌组高度可变，且对环境条件的任何变化都很敏感。根据损伤类型和目标应用，增强治疗因子的分泌是可取的。环境条件调节的变化会影响细胞存活、迁移能力以及增殖和克隆形成潜力。
本研究在含有不同浓度人血小板裂解物（hPL）的培养基中培养脐带华通氏胶来源的MSCs（WJ-MSCs）。创建了两组：一组hPL浓度低，另一组hPL浓度高。通过评估间充质表型保留、分泌活性、克隆形成潜力、增殖和迁移能力，分析了这些不同hPL浓度的影响。此外，还测量了关键治疗因子的分泌水平，如肝细胞生长因子（HGF）、脑源性神经营养因子（BDNF）和趋化因子配体2（CCL-2）。
无论hPL浓度如何，WJ-MSCs都能维持其间充质表型。然而，较高浓度的hPL可促进细胞克隆形成潜力、增殖、迁移，并增加治疗因子的分泌。
调整培养基中的hPL浓度可调节WJ MSCs的反应并增强其治疗潜力。较高的hPL浓度可促进分泌活性增加，并提高WJ-MSCs的再生能力，这表明优化基于MSCs的治疗方法有一个很有前景的策略。
