Capel B, Mintz B
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia Pennsylvania 19111.
Exp Hematol. 1989 Sep;17(8):872-6.
Neonatal unirradiated mice of W-mutant genotypes, with a hematopoietic stem cell defect and anemia, were injected i.v. with normal fetal liver hematopoietic cells. Efficient, long-term engraftment occurred as a result of the competitive advantage to the donor stem cells. The frequency of engraftment and rate of repopulation characteristically diminish in the series W/Wv, Wf/Wf, and Wv/+, in which the severity of the endogenous defect is progressively less. H-2 compatibility is required in the inbred strain combinations examined; other histocompatibility loci play a minor role in some strain combinations. Engraftment is due to self-renewing hematopoietic stem cells ancestral to myeloid and lymphoid lineages. The more mildly defective mutants display much greater variability in the kinetics of repopulation--a result consistent with seeding by single, or very few, stem cells that form developing clones. Engraftment efficiency is reduced by prolonged culture of fetal liver cells during experimental infection by recombinant retroviruses; nevertheless, after 24 h in vitro to achieve retroviral marking, stem cells retain their ability to repopulate and develop in W/Wv neonates.
具有造血干细胞缺陷和贫血的W突变基因型新生未受辐照小鼠经静脉注射正常胎儿肝脏造血细胞。由于供体干细胞具有竞争优势，从而实现了高效、长期的植入。在W/Wv、Wf/Wf和Wv/+系列中，植入频率和再增殖率显著降低，其中内源性缺陷的严重程度逐渐减轻。在所检测的近交系组合中需要H-2相容性；其他组织相容性位点在某些品系组合中起次要作用。植入是由于髓系和淋巴系祖先的自我更新造血干细胞。缺陷较轻的突变体在再增殖动力学上表现出更大的变异性——这一结果与单个或极少数干细胞形成发育克隆的播种情况一致。在重组逆转录病毒实验性感染期间，延长胎儿肝细胞培养会降低植入效率；然而，在体外培养24小时以实现逆转录病毒标记后，干细胞在W/Wv新生小鼠中仍保留其再增殖和发育的能力。
