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SUL-109 Protects Hematopoietic Stem Cells from Apoptosis Induced by Short-Term Hypothermic Preservation and Maintains Their Engraftment Potential.
Biology of Blood and Marrow Transplantation ( IF 5.609 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.bbmt.2019.12.770 Fatima S F Aerts-Kaya 1 , Trudi P Visser 2 , Burcu Pervin 3 , Aynura Mammadova 3 , Özgür Özyüncü 4 , Gerard Wagemaker 2 , F Duygu Uçkan-Çetinkaya 3
Biology of Blood and Marrow Transplantation ( IF 5.609 ) Pub Date : 2020-01-07 , DOI: 10.1016/j.bbmt.2019.12.770 Fatima S F Aerts-Kaya 1 , Trudi P Visser 2 , Burcu Pervin 3 , Aynura Mammadova 3 , Özgür Özyüncü 4 , Gerard Wagemaker 2 , F Duygu Uçkan-Çetinkaya 3
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The newly developed 6-hydroxychromanol derivate SUL-109 was shown to provide protection during hypothermic storage of several cell lines, but has not been evaluated in hematopoietic stem cells (HSCs). Hypothermic preservation of HSCs would be preferred over short-term cryopreservation to prevent cell loss during freezing/thawing and would be particularly useful for short-term storage, such as during conditioning of patients or transport of HSC transplants. Here we cultured human CD34+ umbilical cord blood (UCB) cells and lineage-depleted (Lin-) Balb/c bone marrow (BM) cells for up to 7 days in serum-free HSC expansion medium with hematopoietic growth factors. SUL-109-containing cultures were stored at 4°C for 3 to 14 days. The UCB cells were tested for viability, cell cycle, and reactive oxygen species (ROS). DMSO-cryopreserved Lin- BM cells or Lin- BM cells maintained for 14 days at 4°C were transplanted into RAG2-/- Balb/c mice and engraftment was followed for 6 months. The addition of SUL-109 during the hypothermic storage of expanded CD34+ UCB cells provided a significant improvement in cell survival of the immature CD34+/CD38- fraction after 7 days of hypothermic storage through scavenging of hypothermia-induced ROS and was able to preserve the multilineage capacity of human CD34+ UCB cells for up to 14 days of cold storage. In addition, SUL-109 protected murine BM Lin- cells from 14 days of hypothermic preservation and maintained their engraftment potential after transplantation in immune-deficient RAG2-/- mice. Our data indicate that SUL-109 is a promising novel chemical for use as a protective agent during cold storage of human and murine HSCs to prevent hypothermia-induced apoptosis and promote cell viability.
中文翻译：
SUL-109保护造血干细胞免受短期低温保存引起的凋亡并保持其植入潜能。
新开发的6-羟基苯二酚衍生物SUL-109已显示在几种细胞系的低温保存过程中提供保护，但尚未在造血干细胞（HSC）中进行评估。与短期冷冻保存相比，HSC的低温保存更为可取，以防止在冷冻/融化过程中细胞丢失，并且对于短期保存（例如在对患者进行调理或运输HSC移植物期间）尤其有用。在这里，我们在具有造血生长因子的无血清HSC扩增培养基中培养人CD34 +脐血（UCB）细胞和贫血的（Lin-）Balb / c骨髓（BM）细胞长达7天。将含有SUL-109的培养物在4°C下保存3至14天。测试了UCB细胞的生存力，细胞周期和活性氧（ROS）。将DMSO冷冻保存的Lin-BM细胞或在4℃下保持14天的Lin-BM细胞移植到RAG2-/-Balb / c小鼠中，并植入6个月。在低温储存扩展的CD34 + UCB细胞的过程中添加SUL-109，通过清除低温诱导的ROS，低温保存7天后，未成熟CD34 + / CD38-组分的细胞存活率有了显着提高，并且能够保留多谱系CD34 + UCB细胞的最大保冷能力为14天。此外，SUL-109可在低温保存14天后保护鼠BM Lin细胞，并在免疫缺陷型RAG2-/-小鼠中保持其移植潜能。
更新日期：2020-01-07
中文翻译：
SUL-109保护造血干细胞免受短期低温保存引起的凋亡并保持其植入潜能。
新开发的6-羟基苯二酚衍生物SUL-109已显示在几种细胞系的低温保存过程中提供保护，但尚未在造血干细胞（HSC）中进行评估。与短期冷冻保存相比，HSC的低温保存更为可取，以防止在冷冻/融化过程中细胞丢失，并且对于短期保存（例如在对患者进行调理或运输HSC移植物期间）尤其有用。在这里，我们在具有造血生长因子的无血清HSC扩增培养基中培养人CD34 +脐血（UCB）细胞和贫血的（Lin-）Balb / c骨髓（BM）细胞长达7天。将含有SUL-109的培养物在4°C下保存3至14天。测试了UCB细胞的生存力，细胞周期和活性氧（ROS）。将DMSO冷冻保存的Lin-BM细胞或在4℃下保持14天的Lin-BM细胞移植到RAG2-/-Balb / c小鼠中，并植入6个月。在低温储存扩展的CD34 + UCB细胞的过程中添加SUL-109，通过清除低温诱导的ROS，低温保存7天后，未成熟CD34 + / CD38-组分的细胞存活率有了显着提高，并且能够保留多谱系CD34 + UCB细胞的最大保冷能力为14天。此外，SUL-109可在低温保存14天后保护鼠BM Lin细胞，并在免疫缺陷型RAG2-/-小鼠中保持其移植潜能。
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