Wu D D, Keating A
Toronto Hospital, Ontario, Canada.
Exp Hematol. 1993 Feb;21(2):251-6.
We investigated the engraftment of hematopoietic stem cells in completely untreated transplant recipients to further study hematopoietic cell regulation and for possible inclusion in gene therapy protocols. Untreated female Balb/c recipients received a single infusion of male Balb/c marrow cells. Donor origin of the hematopoietic cells was determined by polymerase chain reaction (PCR), Southern and in situ hybridization analyses with Y-chromosome-specific probes. We found that up to 47% day 12 CFU-S (26.2 +/- 12.6%, mean +/- SD, range 13.3 to 46.7%), 7.3 +/- 5.5% CFU-GM and from 2.5 to approximately 10% nucleated marrow cells were of donor-origin at 8 weeks after marrow infusion. Our results indicate that hematopoietic stem cells can stably engraft in completely unconditioned recipients but, during the interval analyzed, have a low tendency to differentiate. Moreover, the data suggest that under steady-state conditions, niches for primitive hematopoietic cells present in the marrow microenvironment are not saturated, and are readily available. We conclude that the untreated-recipient transplant model, in conjunction with sensitive techniques for the detection of donor cells, provides a valuable means for studying hematopoietic stem cell regulation and indicates a need to reassess our understanding of the interactions between stem cells and the hematopoietic microenvironment.
我们研究了造血干细胞在完全未经处理的移植受者体内的植入情况，以进一步研究造血细胞的调节，并探讨其是否可能纳入基因治疗方案。未经处理的雌性Balb/c受者接受了单次输注的雄性Balb/c骨髓细胞。通过聚合酶链反应（PCR）、Southern杂交以及使用Y染色体特异性探针的原位杂交分析来确定造血细胞的供体来源。我们发现，在骨髓输注后8周时，高达47%的第12天脾集落形成单位（CFU-S）（平均±标准差为26.2±12.6%，范围为13.3%至46.7%）、7.3±5.5%的粒-巨噬细胞集落形成单位（CFU-GM）以及2.5%至约10%的有核骨髓细胞来自供体。我们的结果表明，造血干细胞能够在完全未预处理的受者体内稳定植入，但在所分析的时间段内，其分化倾向较低。此外，数据表明在稳态条件下，骨髓微环境中存在的原始造血细胞龛并未饱和，且易于利用。我们得出结论，未经处理的受者移植模型，结合检测供体细胞的敏感技术，为研究造血干细胞调节提供了一种有价值的手段，并表明有必要重新评估我们对干细胞与造血微环境之间相互作用的理解。
