Donnelly D S, Zelterman D, Sharkis S, Krause D S
Department of Laboratory Medicine, Yale University School of Medicine and Yale New Haven Hospital, CT 06520-8035, USA.
Exp Hematol. 1999 May;27(5):788-96. doi: 10.1016/s0301-472x(99)00032-6.
The transmembrane glycoprotein CD34 is expressed on human hematopoietic stem cells and committed progenitors in the bone marrow, and CD34-positive selection currently is used to isolate bone marrow repopulating cells in clinical transplantation protocols. Recently, CD34- hematopoietic stem cells were described in both humans and mice, and it was suggested that CD34+ murine bone marrow cells may lack long-term reconstituting ability. In this study, the long-term repopulating ability of CD34+Lin- vs CD34-Lin- cells was compared directly using syngeneic murine bone marrow transplantation. Highly purified populations of CD34+Lin- and CD34-Lin- cells each are able to reconstitute bone marrow, confirming that both populations contain hematopoietic stem cells; however, the number of hematopoietic stem cells in the CD34+Lin- fraction is approximately 100-fold greater than the number in the CD34-Lin- fraction. In competitive repopulation experiments, CD34+ stem cells are better able to engraft the bone marrow than are CD34- cells. CD34+Lin- cells provide both short- and long-term engraftment, but the CD34-Lin- cells are capable of only long-term engraftment. Ex vivo, the CD34+Lin- stem cells expand over 3 days in culture and maintain the ability to durably engraft animals in a serial transplant model. In contrast, when CD34-Lin- cells are cultured using the same conditions ex vivo, the cell number decreases, and the cells do not retain the ability to repopulate the bone marrow. Thus, the CD34+Lin- and CD34-Lin- cells constitute two functionally distinct populations that are capable of long-term bone marrow reconstitution.
跨膜糖蛋白CD34在人类造血干细胞及骨髓中定向祖细胞上表达，目前在临床移植方案中，CD34阳性选择用于分离骨髓重建细胞。最近，在人类和小鼠中均发现了CD34-造血干细胞，有人提出CD34+小鼠骨髓细胞可能缺乏长期重建能力。在本研究中，使用同基因小鼠骨髓移植直接比较了CD34+Lin-细胞与CD34-Lin-细胞的长期重建能力。高度纯化的CD34+Lin-细胞群和CD34-Lin-细胞群均能够重建骨髓，证实这两个细胞群均含有造血干细胞；然而，CD34+Lin-组分中的造血干细胞数量比CD34-Lin-组分中的数量大约多100倍。在竞争性重建实验中，CD34+干细胞比CD34-细胞更能植入骨髓。CD34+Lin-细胞可提供短期和长期植入，但CD34-Lin-细胞仅能长期植入。在体外，CD34+Lin-干细胞在培养3天内会扩增，并在连续移植模型中保持持久植入动物的能力。相比之下，当在相同条件下体外培养CD34-Lin-细胞时，细胞数量会减少，且这些细胞不再保留重建骨髓的能力。因此，CD34+Lin-细胞和CD34-Lin-细胞构成了两个功能不同但都能够长期重建骨髓的细胞群。
