Zanjani E D, Almeida-Porada G, Flake A W
Department of Medicine, Department of Veterans Affairs Medical Center, Medicine, Reno, NV 89520, USA.
Stem Cells. 1995 Mar;13(2):101-11. doi: 10.1002/stem.5530130202.
We have taken advantage of the permissive environment of the early gestational age fetus to engraft human hematopoietic stem cells (HSC) into preimmune fetal lambs. The resulting chimeras exhibit long-term multilineage engraftment of human cells in the bone marrow (BM) and peripheral blood (PB). Long-term multilineage reconstitution of second generation recipients by human cells isolated from chimeric sheep BM indicates that the engraftment in this model involved long-term repopulating human HSC. The model appears to be sensitive enough to detect relatively small numbers of transplanted HSC from pre- and postnatal human sources. Finally, transplantation of mature T lymphocyte-containing cells from a variety of sources results in lethal graft-versus-host disease (GVHD), analogous to clinical BM transplantation, suggesting that, at least in some respects, the model is biologically relevant. The human-sheep model is promising and may have important advantages over murine models for the in vivo study of normal and abnormal hematopoiesis and as a potential assay system for human HSC.
我们利用孕早期胎儿的宽松环境，将人类造血干细胞（HSC）植入未产生免疫反应的胎儿羔羊体内。由此产生的嵌合体在骨髓（BM）和外周血（PB）中表现出人类细胞的长期多谱系植入。从嵌合羊骨髓中分离出的人类细胞对第二代受体进行长期多谱系重建，表明该模型中的植入涉及长期重建造血干细胞的人类HSC。该模型似乎足够敏感，能够检测出来自产前和产后人类来源的相对少量移植HSC。最后，移植来自各种来源的含有成熟T淋巴细胞的细胞会导致致命的移植物抗宿主病（GVHD），类似于临床骨髓移植，这表明至少在某些方面，该模型具有生物学相关性。人羊模型很有前景，在正常和异常造血的体内研究以及作为人类HSC的潜在检测系统方面，可能比小鼠模型具有重要优势。
