Brümmendorf T H, Rufer N, Baerlocher G M, Roosnek E, Lansdorp P M
Division of Hematology, Oncology and Immunology, University of Tübingen, D-72076 Tübingen, Germany.
Ann N Y Acad Sci. 2001 Jun;938:1-7; discussion 7-8. doi: 10.1111/j.1749-6632.2001.tb03568.x.
The number of cell divisions in hematopoietic stem cells (HSCs) following transplantation of bone marrow or mobilized peripheral blood into myelo-ablated recipients is unknown. This number is expected to depend primarily on the number of transplanted stem cells, assuming that stem cells do not differ in engraftment potential and other functional properties. In a previous study, we found that the telomere length in circulating granulocytes in normal individuals shows a biphasic decline with age, most likely reflecting age-related changes in the turnover of HSCs. In order to study HSCs' proliferation kinetics following stem cells transplantation, we analyzed the telomere length in donor-derived nucleated blood cells in four HLA-matched bone marrow transplant recipients relative to comparable cells from the sibling donors. In each case, the telomeres in granulocytes were shorter in the recipient than in the donor. This difference was established in the first year post transplantation and did not change after that. The telomere length in naïve and memory T cells showed marked differences after transplantation, complicating the interpretation of telomere length data using unseparated nucleated blood cells. Interestingly, the telomere length in naïve T cells that were first observed six months post transplantation was very similar in donor and recipient pairs. Our observations are compatible with a limited number of additional cell divisions in stem cell populations after bone marrow transplantations and support the idea that different populations of stem cells contribute to short-term myeloid and long-term lympho myeloid hematopoiesis.
将骨髓或动员的外周血移植到接受过骨髓消融的受者体内后，造血干细胞（HSC）的细胞分裂次数尚不清楚。假设干细胞在植入潜力和其他功能特性方面没有差异，那么这个次数预计主要取决于移植的干细胞数量。在之前的一项研究中，我们发现正常个体循环粒细胞中的端粒长度随年龄呈双相下降，这很可能反映了造血干细胞更新中与年龄相关的变化。为了研究干细胞移植后造血干细胞的增殖动力学，我们分析了4名HLA匹配的骨髓移植受者中供体来源的有核血细胞的端粒长度，并与来自同胞供体的可比细胞进行了比较。在每种情况下，受者粒细胞中的端粒都比供体中的短。这种差异在移植后的第一年就已确定，之后没有变化。移植后，初始T细胞和记忆T细胞中的端粒长度显示出明显差异，这使得使用未分离的有核血细胞来解释端粒长度数据变得复杂。有趣的是，移植后6个月首次观察到的初始T细胞中的端粒长度在供体和受体对中非常相似。我们的观察结果与骨髓移植后干细胞群体中有限数量的额外细胞分裂情况相符，并支持不同干细胞群体对短期髓系和长期淋巴髓系造血有贡献的观点。
