Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies.

Quantification of the Culture Stability of Stem Cell Fractions from Oral-Derived, Human Mesenchymal Stem Cell Preparations: A Significant Step toward the Clinical Translation of Cell Therapies.
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DOI:
10.3390/cells12232703
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发表时间:
2023-11-25
期刊:
影响因子:
6
通讯作者:
--
中科院分区:
生物学2区
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在可预测干细胞疗法(sct)的开发和利用中,一个持续的限制和主要挑战是确定干细胞的最佳剂量。在此,我们报告了来自口腔组织的人间充质干细胞(MSC)制剂的干细胞组分(SCF)的定量。一种新的计算方法,动态干细胞(KSC)计数,用于量化8例患者口腔牙槽骨源性MSC (aBMSCs)中干细胞的SCF和特异性细胞培养动力学。这些分析首次证实,这些异质、混合细胞群体中的SCF在供者之间存在显著差异,从7%到77%不等(方差分析p < 0.0001)。无论是aBMSC制剂的初始SCF,还是连续培养后SCF水平随时间的变化,都显示出供体间的高度差异。因此,研究表明,在连续细胞培养过程中,人aBMSC制剂的SCF稳定性在供者之间存在差异,一些患者制剂具有足够的稳定性,可以支持干细胞的长期净扩增。这些发现为MSCs的临床规模扩展和生物制造提供了重要的见解,有助于在临床试验和采用SCT的治疗中建立更有效和可预测的结果。
A continuing limitation and major challenge in the development and utilization of predictable stem cell therapies (SCTs) is the determination of the optimal dosages of stem cells. Herein, we report the quantification of stem cell fractions (SCF) of human mesenchymal stem cell (MSC) preparations derived from oral tissues. A novel computational methodology, kinetic stem cell (KSC) counting, was used to quantify the SCF and specific cell culture kinetics of stem cells in oral alveolar bone-derived MSC (aBMSCs) from eight patients. These analyses established, for the first time, that the SCF within these heterogeneous, mixed-cell populations differs significantly among donors, ranging from 7% to 77% (ANOVA p < 0.0001). Both the initial SCF of aBMSC preparations and changes in the level of the SCF with serial culture over time showed a high degree of inter-donor variation. Hence, it was revealed that the stability of the SCF of human aBMSC preparations during serial cell culture shows inter-donor variation, with some patient preparations exhibiting sufficient stability to support the long-term net expansion of stem cells. These findings provide important insights for the clinical-scale expansion and biomanufacturing of MSCs, which can facilitate establishing more effective and predictable outcomes in clinical trials and treatments employing SCT.
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