Department of Dermatology, Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
Sci Rep. 2020 Nov 12;10(1):19671. doi: 10.1038/s41598-020-76760-5.
Human umbilical cord blood (hUCB)-derived hematopoietic stem cells (HSCs) are an important source for HSCs in allogeneic HSC transplantation, but a limited number and a low efficacy of engraftment greatly restrict their clinical use. Here, we report the ability of photobiomodulation therapy (PBMT) to significantly enhance the engraftment efficacy of hUCB HSCs and progenitor cells (HSPCs). hUCB CD34 cells were illuminated at a fluence of 2 J/cm with a near-infrared light (830 nm) transmitted by an array of light-emitting diodes (LED) prior to infusion of NOD/SCID-IL2Rγ mice. The pre-treatment resulted in a threefold higher of the mean percentage of human CD45 cells in the periphery of the mice compared to sham-treated CD34 cells. The enhanced engraftment may result from a PBMT-mediated increase of intracellular reactive oxygen species (ROS) levels and Src protein phosphorylation in CD34 cells. The two events were causally related as suggested by the finding that elevation of ROS by hydrogen peroxide increased Src phosphorylation, while ROS reduction by N-acetyl cysteine partially reversed the phosphorylation. The investigation demonstrates that PBMT can promote engraftment of hUCB HPSCs, at least in part, via ROS-mediated Src signaling pathway. PBMT can be potentially a safe, convenient, and cost-effective modality to improve hematological reconstitution in patients.
人脐带血（hUCB）来源的造血干细胞（HSCs）是异基因 HSC 移植中 HSCs 的重要来源，但数量有限和植入效率低极大地限制了其临床应用。在这里，我们报告了光生物调节疗法（PBMT）显著增强 hUCB HSCs 和祖细胞（HSPCs）植入效率的能力。在将 NOD/SCID-IL2Rγ 小鼠输注 hUCB CD34 细胞之前，用发光二极管（LED）阵列传输的近红外光（830nm）对 CD34 细胞进行 2J/cm2 的辐照。与 sham 处理的 CD34 细胞相比，预处理导致小鼠外周血中人类 CD45 细胞的平均百分比增加了三倍。这种增强的植入可能是由于 PBMT 介导的 CD34 细胞内活性氧（ROS）水平和Src 蛋白磷酸化增加所致。这两个事件是因果相关的，因为发现过氧化氢升高 ROS 会增加 Src 磷酸化，而 N-乙酰半胱氨酸降低 ROS 会部分逆转磷酸化。该研究表明，PBMT 可以通过 ROS 介导的 Src 信号通路促进 hUCB HSPCs 的植入，至少部分如此。PBMT 可能是一种安全、方便且具有成本效益的方式，可以改善患者的血液重建。
