Körbling M, Champlin R
University of Texas MD Anderson Cancer Center, Department of Hematology, Houston.
Stem Cells. 1996 Mar;14(2):185-95. doi: 10.1002/stem.140185.
Circulating hematopoietic progenitor cells include pluripotent stem cells expressing indefinite self-renewal capacity and, therefore, can be used for restoring hematopoiesis following myeloablative treatment. A transient shifting of progenitor cells from extravascular sites into the circulation by chemopriming and/or cytokine treatment enables the collection by apheresis of a sufficient number of progenitor cells to guarantee engraftment. The addition of new cytokines (e.g., thrombopoietin) and large volume apheresis will increase peripheral blood progenitor cell (PBPC) procurement efficiency, whereas the risk of concurrently mobilizing clonogenic tumor cells in patients with solid tumors and hematologic malignancies remains to be carefully evaluated. As compared with bone marrow (BM) progenitor cells, the use of PBPCs significantly shortens the recovery of WBC and platelets following transplantation. Most recently, successful allogeneic transplantation of PBPCs has been reported without increasing the incidence and severity of acute graft-versus-host-disease. Due to the more than one log higher number of lymphoid subsets contained in a PBPC allograft, one might expect a more pronounced graft-versus-leukemia effect in the transplant patient. Similar to BM cells, ex vivo manipulation of mobilized apheresis products is used or being developed (ultralight density percoll gradient, CD8 depletion, selection of graft facilitating cells, CD34+ cell purification and others). The transduction and long-term expression of marker genes and, most recently, therapeutic genes (e.g., MDR-1) in PBPCs have been successfully demonstrated by several groups in patients with hematologic malignancies and selected solid tumors. It is expected that, based on the easier procurement of hematopoietic stem cells and advantageous engraftment characteristics, PBPCs in both autologous and allogeneic transplant situations will eventually replace BM-derived progenitor cells.
循环造血祖细胞包括具有无限自我更新能力的多能干细胞，因此可用于在清髓治疗后恢复造血功能。通过化学预激和/或细胞因子处理使祖细胞从血管外部位短暂转移至循环中，能够通过单采术收集足够数量的祖细胞以确保植入。添加新的细胞因子（如血小板生成素）和大容量单采术将提高外周血祖细胞（PBPC）的采集效率，而在实体瘤和血液系统恶性肿瘤患者中同时动员克隆性肿瘤细胞的风险仍有待仔细评估。与骨髓（BM）祖细胞相比，使用PBPC可显著缩短移植后白细胞和血小板的恢复时间。最近，有报道称PBPC的同种异体移植成功，且未增加急性移植物抗宿主病的发生率和严重程度。由于PBPC同种异体移植物中所含淋巴亚群的数量高出一个对数级以上，人们可能预期在移植患者中会有更明显的移植物抗白血病效应。与BM细胞类似，对动员的单采产物进行体外操作正在被使用或开发中（超轻密度Percoll梯度、CD8去除、移植物促进细胞的选择、CD34+细胞纯化等）。几个研究小组已在血液系统恶性肿瘤患者和部分实体瘤患者中成功证明了PBPC中标记基因以及最近治疗基因（如多药耐药基因1）的转导和长期表达。基于造血干细胞更容易采集以及有利的植入特性，预计在自体和同种异体移植情况下，PBPC最终将取代BM来源的祖细胞。
