Harrison D E, Astle C M
J Exp Med. 1982 Dec 1;156(6):1767-79. doi: 10.1084/jem.156.6.1767.
Long-term functional capacities of marrow cell lines were defined by competitive repopulation, a technique capable of detecting a small decline in repopulating abilities. There was little or no difference between cells from old and young donors, but a single serial transplantation caused a large decline in repopulating ability. Varying the numbers of marrow cells transplanted into the initial carrier from 10(5) to 10(7) did not alter the ability of the carrier's marrow cells to repopulate in competition with previously untransplanted cells. This ability was improved only in carriers that had received 10(8) marrow cells, although deleterious effects of transplantation were still present. These effects were not solely caused by cell damage from the transplantation procedure, because transplantation by parabiosis, or recovery from sublethal irradiation without transplantation, reduced repopulating abilities as much as transplanting 10(5) to 10(7) marrow cells. The transplantation effect also was not caused solely by irradiation, because the same effect appeared in unirradiated W/Wv carriers. The transplantation effect was more pronounced when donors were identified by hemoglobin type than by chromosome markers, implying that nonerythroid cell lines may be less affected by transplantation than erythroid precursor cells. When the effects of a lifetime of normal function and a single transplantation were compared, the latter caused 3-7 times more decline in repopulating abilities of phytohemagglutinin-responsive cell precursors, and at least 10-20 times more decline in erythroid cell precursors. Stem cell lines can be serially transplanted at least five times before losing their ability to repopulate and save lethally irradiated recipients or to cure genetically anemic mice. Therefore, if transplantation causes an acceleration of the normal aging process, these figures suggest that stem cells should be able to function normally through at least 15-50 life spans.
骨髓细胞系的长期功能能力通过竞争性再增殖来定义，这是一种能够检测再增殖能力微小下降的技术。老年和年轻供体的细胞之间几乎没有差异，但单次连续移植会导致再增殖能力大幅下降。将移植到初始受体中的骨髓细胞数量从10⁵ 改变到10⁷ ，并未改变受体骨髓细胞与先前未移植细胞竞争时的再增殖能力。只有在接受了10⁸ 个骨髓细胞的受体中，这种能力才得到改善，不过移植的有害影响仍然存在。这些影响并非仅仅由移植过程中的细胞损伤引起，因为联体共生移植或未移植情况下从亚致死剂量照射中恢复，与移植10⁵ 至10⁷ 个骨髓细胞一样，都会降低再增殖能力。移植效应也并非仅仅由辐射引起，因为在未受辐射的W/Wv受体中也出现了相同的效应。当根据血红蛋白类型而非染色体标记来识别供体时，移植效应更为明显，这意味着非红系细胞系可能比红系前体细胞受移植的影响更小。当比较正常功能一生的影响和单次移植的影响时，后者导致植物血凝素反应性细胞前体的再增殖能力下降3至7倍，红系细胞前体的再增殖能力下降至少10至20倍。干细胞系在失去再增殖能力以及挽救受致死性照射的受体或治愈遗传性贫血小鼠的能力之前，至少可以连续移植五次。因此，如果移植会加速正常衰老过程，这些数据表明干细胞应该能够正常发挥功能至少15至50个寿命周期。
