Theilgaard-Mönch K, Raaschou-Jensen K, Andersen H, Russell C A, Vindeløv L, Jacobsen N, Dickmeiss E
Department of Hematology, The Finsen Center, Rigshospitalet, University of Copenhagen, Denmark.
Bone Marrow Transplant. 1999 Feb;23(3):243-9. doi: 10.1038/sj.bmt.1701579.
Cytokine-mobilized peripheral blood progenitor cells (PBPCs) have been used successfully for hematopoietic reconstitution following allogeneic transplantation. The ease of harvest, the faster engraftment and the high yield of CD34+ cells have made this source of hematopoietic progenitor cells (HPCs) an attractive alternative to bone marrow (BM). In the present study we compared the engraftment potential of conventional BM allografts and single leukapheresis products (LPs) collected from healthy donors following the administration of granulocyte colony-stimulating factor (G-CSF). For this, lineage-committed and primitive HPCs were assessed by flow cytometry and by colony- and cobblestone area-forming cell (CFC, CAFC) assays. Mean numbers of CD34+ cells in LPs (n = 11) were similar to that of BM grafts (n = 12) (278+/-57 vs 227+/-34 x 10(6) CD34+ cells). The frequencies of CFCs, week 5 CAFCs and week 8 CAFCs were 1.6-, 8.4- and 10.3-fold higher in the CD34+ compartment of mobilized blood than that of marrow, resulting in significantly higher yields of clonogenic HPCs in LPs when compared to BM grafts. We conclude that G-CSF preferentially mobilizes clonogenic progenitors capable of short- and, in particular, longterm reconstitution, and that the engraftment potential of single LPs is superior to that of BM allografts. Hence, the use of PBPCs may be favorable for protocols that include graft manipulations with expected cell loss (eg T cell depletion, CD34+ selection). PBPCs may also be advantageous for gene therapy trials due to their high numbers of potential target cells (eg CAFCs).
细胞因子动员的外周血祖细胞(PBPCs)已成功用于异基因移植后的造血重建。采集方便、植入更快以及CD34+细胞产量高,使得这种造血祖细胞(HPCs)来源成为骨髓(BM)的一个有吸引力的替代选择。在本研究中,我们比较了常规骨髓同种异体移植物和从健康供体在给予粒细胞集落刺激因子(G-CSF)后采集的单次白细胞分离产品(LPs)的植入潜力。为此,通过流式细胞术以及集落形成细胞和鹅卵石区形成细胞(CFC、CAFC)测定法评估了定向祖细胞和原始HPCs。LPs(n = 11)中CD34+细胞的平均数量与骨髓移植物(n = 12)相似(278±57对227±34×10⁶个CD34+细胞)。动员血液中CD34+区室的CFCs、第5周CAFCs和第8周CAFCs频率分别比骨髓中的高1.6倍、8.4倍和10.3倍,与骨髓移植物相比,LPs中克隆形成性HPCs的产量显著更高。我们得出结论,G-CSF优先动员能够进行短期尤其是长期重建的克隆形成祖细胞,并且单次LPs的植入潜力优于骨髓同种异体移植物。因此,对于包括预期有细胞损失的移植物操作(如T细胞去除、CD34+选择)的方案,使用PBPCs可能是有利的。由于PBPCs有大量潜在靶细胞(如CAFCs),它们在基因治疗试验中也可能具有优势。