Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
PLoS One. 2009 Dec 31;4(12):e8489. doi: 10.1371/journal.pone.0008489.
Mouse models of human disease are invaluable for determining the differentiation ability and functional capacity of stem cells. The best example is bone marrow transplants for studies of hematopoietic stem cells. For organ studies, the interpretation of the data can be difficult as transdifferentiation, cell fusion or surface antigen transfer (trogocytosis) can be misinterpreted as differentiation. These events have not been investigated in hematopoietic stem cell transplant models.
METHODOLOGY/PRINCIPAL FINDINGS: In this study we investigated fusion and trogocytosis involving blood cells during bone marrow transplantation using a xenograft model. We report that using a standard SCID repopulating assay almost 100% of the human donor cells appear as hybrid blood cells containing both mouse and human surface antigens.
CONCLUSION/SIGNIFICANCE: Hybrid cells are not the result of cell-cell fusion events but appear to be due to efficient surface antigen transfer, a process referred to as trogocytosis. Antigen transfer appears to be non-random and includes all donor cells regardless of sub-type. We also demonstrate that irradiation preconditioning enhances the frequency of hybrid cells and that trogocytosis is evident in non-blood cells in chimera mice.
人类疾病的小鼠模型对于确定干细胞的分化能力和功能能力非常宝贵。最好的例子是骨髓移植用于造血干细胞的研究。对于器官研究,由于转分化、细胞融合或表面抗原转移(噬血细胞)可能被误解为分化,因此数据的解释可能很困难。这些事件在造血干细胞移植模型中尚未得到研究。
方法/主要发现:在这项研究中,我们使用异种移植模型研究了骨髓移植过程中涉及血细胞的融合和噬血细胞现象。我们报告说,使用标准的 SCID 重建造血测定,几乎 100%的人类供体细胞表现为含有小鼠和人类表面抗原的混合血细胞。
结论/意义:杂交细胞不是细胞-细胞融合事件的结果,而是似乎是由于有效的表面抗原转移,这一过程被称为噬血细胞。抗原转移似乎不是随机的,包括所有供体细胞,无论亚型如何。我们还证明,辐照预处理增强了杂交细胞的频率,并且在嵌合体小鼠中的非血细胞中也可见噬血细胞现象。