Aging is associated with increased morbidity and high economic costs due to a burdened healthcare system and decreased workforce. Parabiotic animal models indicated that secretome from young cells can restore aged tissue functions. We used a heterochronic co-culture system with young and aged mobilized peripheral blood (MPB) or umbilical cord blood (UCB) and showed hematopoietic restoration, independent of allogeneic difference. Bidirectional communication between the aged and young cells influenced the miRNA cargo of exosomes, resulting in partial reprograming of the aged cells. The restored cells enhanced hematopoiesis (e.g., increased lymphoid:myeloid ratio) in immunodeficient mice bearing autologous aged hematopoietic system. Four exosomal miRNAs targeting PAX and PPMIF were partly responsible for the hematopoietic rejuvenation. Notably, increased natural killer (NK) cells within the restored cells eliminated dormant breast cancer cells in vivo. The findings could be developed as preventive measure and treatment for sustained immune/hematopoietic competence with potential for immunotherapy.

中文翻译：

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人源化小鼠模型中外来体介导的造血修复表明癌症免疫疗法的潜力

由于医疗系统负担沉重和劳动力减少，老龄化与发病率增加和较高的经济成本有关。副生物动物模型表明，年轻细胞的分泌组可以恢复衰老的组织功能。我们将异时共培养系统与年轻和老年的动员外周血（MPB）或脐带血（UCB）结合使用，并显示出造血功能的恢复，而不受同种异体差异的影响。老细胞和年轻细胞之间的双向通讯影响了外泌体的miRNA转运，导致了老细胞的部分重编程。在携带自体年老造血系统的免疫缺陷小鼠中，恢复的细胞增强了造血功能（例如，增加了淋巴：髓样比例）。靶向PAX和PPMIF的四个外泌体miRNA部分负责造血复兴。值得注意的是 恢复的细胞内增加的自然杀伤（NK）细胞消除了体内休眠的乳腺癌细胞。该发现可作为预防措施和持续免疫/造血能力的治疗方法，并具有免疫治疗的潜力。