University of Strasbourg, INSERM, EFS Grand-Est, BPPS UMR-S1255, Strasbourg, France.
Université de Lorraine, CITHEFOR, F-54505, Vandoeuvre Les Nancy, France.
Cell Death Dis. 2024 May 1;15(5):305. doi: 10.1038/s41419-024-06682-x.
Zebrafish is widely adopted as a grafting model for studying human development and diseases. Current zebrafish xenotransplantations are performed using embryo recipients, as the adaptive immune system, responsible for host versus graft rejection, only reaches maturity at juvenile stage. However, transplanted primary human hematopoietic stem/progenitor cells (HSC) rapidly disappear even in zebrafish embryos, suggesting that another barrier to transplantation exists before the onset of adaptive immunity. Here, using a labelled macrophage zebrafish line, we demonstrated that engraftment of human HSC induces a massive recruitment of macrophages which rapidly phagocyte transplanted cells. Macrophages depletion, by chemical or pharmacological treatments, significantly improved the uptake and survival of transplanted cells, demonstrating the crucial implication of these innate immune cells for the successful engraftment of human cells in zebrafish. Beyond identifying the reasons for human hematopoietic cell engraftment failure, this work images the fate of human cells in real time over several days in macrophage-depleted zebrafish embryos.
斑马鱼被广泛应用于研究人类发育和疾病的移植模型。目前的斑马鱼异种移植是在胚胎受体中进行的，因为负责宿主与移植物排斥反应的适应性免疫系统仅在幼年阶段成熟。然而，即使在斑马鱼胚胎中，移植的原发性人造血干细胞/祖细胞（HSC）也会迅速消失，这表明在适应性免疫开始之前存在另一个移植障碍。在这里，我们使用标记的巨噬细胞斑马鱼系证明，人 HSC 的植入会引起大量巨噬细胞的募集，这些巨噬细胞会迅速吞噬移植细胞。通过化学或药理学处理耗尽巨噬细胞，显著提高了移植细胞的摄取和存活，表明这些先天免疫细胞对人细胞在斑马鱼中的成功植入具有至关重要的意义。除了确定人造血细胞植入失败的原因外，这项工作还在巨噬细胞耗尽的斑马鱼胚胎中实时观察了人细胞数天的命运。
