Tai Tzong-Shyuan, Chen Yun-Hsiang, Yao Chao-Ling, Lin Jiun-Han, Yang Yu-Shao, Shi Jai-Wen, Fang Li-Wen, Hsu Duen-Wei, Kuo Shu-Chen, Hsu Shu-Ching
Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan.
Department of Life Science, Fu-Jen Catholic University, New Taipei City, 242062, Taiwan.
BMC Med. 2025 Mar 18;23(1):164. doi: 10.1186/s12916-025-03987-2.
Hematopoietic stem cell transplantation (HSCT) is a critical treatment for hematologic disorders such as leukemia, lymphoma, and specific immune deficiencies. Despite its efficacy, challenges such as engraftment failure and delayed neutrophil regeneration remain significant barriers. These complications lead to prolonged cytopenia, increased risks of infections and other complications, and elevated morbidity and mortality rates. While mesenchymal stem cells (MSCs) are known to play essential roles in supporting hematopoiesis, the precise mechanisms and interactions between MSCs and other cellular components in HSCT require further investigation.
To address these challenges, we explored the combined infusion of allotype-cord blood hematopoietic stem cells (HSCs) and activated T cells from the same donor along with third-party MSCs. The study assessed the effects of this triple-cell therapy on neutrophil differentiation and function ex vivo and in vivo. Using a respiratory infection model, we evaluated the accumulation of human neutrophils, cytokine secretion (IL-6 and IL-8), bacterial clearance, and overall survival compared to control groups.
The triple-cell therapy demonstrated a significant improvement in the differentiation of human HSCs into neutrophils both in ex vivo and in vivo. In the respiratory infection model, this approach resulted in enhanced accumulation of human neutrophils, increased secretion of IL-6 and IL-8, superior bacterial clearance, and reduced mortality rates compared to the control group. These findings highlight the synergistic interplay between allo-HSCs, MSCs, and activated T cells in promoting neutrophil production and function.
Our study presents a novel therapeutic strategy combining allo-HSCs, activated T cells, and third-party MSCs to enhance neutrophil production and functionality post-transplantation. This approach not only accelerates neutrophil regeneration but also improves resistance to infections, offering a promising avenue to overcome engraftment challenges in HSCT.
造血干细胞移植（HSCT）是治疗白血病、淋巴瘤和特定免疫缺陷等血液系统疾病的关键方法。尽管其疗效显著，但植入失败和中性粒细胞再生延迟等挑战仍然是重大障碍。这些并发症导致血细胞减少期延长、感染及其他并发症风险增加，以及发病率和死亡率上升。虽然已知间充质干细胞（MSCs）在支持造血过程中发挥重要作用，但MSCs与HSCT中其他细胞成分之间的确切机制和相互作用仍需进一步研究。
为应对这些挑战，我们探索了联合输注来自同一供体的同种异体脐血造血干细胞（HSCs）、活化T细胞以及第三方MSCs。该研究评估了这种三细胞疗法在体外和体内对中性粒细胞分化和功能的影响。使用呼吸道感染模型，我们评估了与对照组相比人类中性粒细胞的积聚、细胞因子分泌（IL-6和IL-8）、细菌清除以及总体生存率。
三细胞疗法在体外和体内均显示出人类HSCs向中性粒细胞分化的显著改善。在呼吸道感染模型中，与对照组相比，这种方法导致人类中性粒细胞积聚增加、IL-6和IL-8分泌增加、细菌清除效果更佳以及死亡率降低。这些发现突出了同种异体HSCs、MSCs和活化T细胞在促进中性粒细胞生成和功能方面的协同相互作用。
我们的研究提出了一种联合同种异体HSCs、活化T细胞和第三方MSCs的新型治疗策略，以增强移植后中性粒细胞的生成和功能。这种方法不仅加速中性粒细胞再生，还提高抗感染能力，为克服HSCT中的植入挑战提供了一条有前景的途径。
