Short-term Rho-associated kinase inhibitor treatment accelerates primary keratinocyte growth while preserving stem cell characteristics
Short-term Rho-associated kinase inhibitor treatment accelerates primary keratinocyte growth while preserving stem cell characteristics
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短期 Rho 相关激酶抑制剂治疗可加速原代角质形成细胞生长，同时保留干细胞特征
DOI：
10.1101/2022.06.28.497914
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Jayarajan V
中科院分区：
文献类型：
--
作者：
Jayarajan V
体细胞干细胞可以在体外培养，并在细胞和基因治疗方面具有吸引力，但体细胞干细胞在体外培养中生长缓慢，影响其存活和干细胞性，并阻碍其临床应用。Rho相关激酶抑制剂（ROCKi）已被用于克服这些障碍。然而，它有可能改变干细胞的特性。我们发现用ROCKi Y-27632培养六天的原代角质形成干细胞（KSC）表现出快速增殖，同时保持分化能力。重要的是，在ROCKi治疗停止后，KSC的数量和特征与未治疗的培养物中的KSC数量和特征无法区分。我们进一步证实ROCKi处理导致AKT和ERK通路的激活，这可以支持角质形成细胞中的细胞存活和增殖。因此，我们得出结论，短期ROCKi治疗加速角质形成细胞扩增不会耗尽KSC的自我更新和分化能力，为临床应用提供了一种安全的途径。
Somatic stem cells can be culturedin-vitroand are attractive for cell and gene therapies, but their slow growth inin-vitroculture affects survival and stemness and hinders clinical applications. Rho-associated kinase inhibitor (ROCKi) has been used to overcome these obstacles. However, it risks changing the characteristics of stem cells. We found that primary keratinocyte stem cells (KSCs) cultured with the ROCKi Y-27632 for six days exhibited rapid proliferation while maintaining the ability to differentiate. Importantly, after discontinuation of ROCKi treatment, KSC numbers and characteristics were indistinguishable from those in non-treated cultures. We further confirmed that ROCKi treatment resulted in the activation of AKT and ERK pathways, which could support cell survival and proliferation in keratinocytes. We thus concluded that accelerating keratinocyte expansion with short-term ROCKi treatment does not exhaust KSCs’ self-renewal and differentiation capacities, presenting a safe avenue for clinical applications.
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