Assessment of the Dose-Dependent Effect of Human Platelet Lysate on Wharton's Jelly-Derived Mesenchymal Stem/Stromal Cells Culture for Manufacturing Protocols.

IF 1.7 Q4 CELL BIOLOGY Stem Cells and Cloning-Advances and Applications Pub Date : 2024-10-05 eCollection Date: 2024-01-01 DOI:10.2147/SCCAA.S471118
Aleksandra Bzinkowska, Anna Sarnowska
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Abstract

Introduction: 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.

Materials and methods: 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.

Results: 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.

Conclusion: 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.

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评估人血小板裂解液对沃顿果冻衍生间充质干细胞/基质细胞培养的剂量依赖性影响,以用于制造规程。
导言:与其他药物相比,间充质干细胞/间质干细胞(MSCs)为基础的产品具有独特的特性,因为其效果因培养条件和微环境而异。在某些情况下,细胞可以单独生产,一次生产一批,用于个性化治疗。因此,根据《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。间充质干细胞的特性已被用作再生医学的潜在细胞疗法。间充质干细胞的保护和再生作用的主要机制是基于其分泌活性。同时,间充质干细胞的分泌组变化多端,对环境条件的任何变化都非常敏感。根据损伤类型和目标应用,加强治疗因子的分泌是可取的。环境条件调节的变化会影响存活率、迁移能力以及增殖和克隆潜力:本研究在含有不同浓度人血小板裂解液(hPL)的培养基中培养沃顿果冻衍生间充质干细胞(WJ-MSCs)。共分为两组:一组为低浓度 hPL,另一组为高浓度 hPL。通过评估间充质表型保持率、分泌活性、克隆潜能、增殖和迁移能力,分析了不同浓度 hPL 的影响。此外,还测定了肝细胞生长因子(HGF)、脑源神经营养因子(BDNF)和趋化因子配体 2(CCL-2)等关键治疗因子的分泌水平:结果:无论 hPL 的浓度如何,WJ-间充质干细胞都能保持其间充质表型。结果:无论 hPL 的浓度如何,WJ-间充质干细胞都能保持间充质表型,但较高浓度的 hPL 能促进细胞的克隆生成潜能、增殖、迁移和治疗因子分泌的增加:结论:调整培养基中的 hPL 浓度可调节 WJ 间充质干细胞的反应并提高其治疗潜力。较高的 hPL 浓度可促进分泌活性的增加,提高 WJ 间充质干细胞的再生能力,为优化基于间充质干细胞的疗法提供了一种有前景的策略。
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来源期刊
CiteScore
6.50
自引率
0.00%
发文量
10
审稿时长
16 weeks
期刊最新文献
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