Broxmeyer H E, Hangoc G, Cooper S, Ribeiro R C, Graves V, Yoder M, Wagner J, Vadhan-Raj S, Benninger L, Rubinstein P
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202.
Proc Natl Acad Sci U S A. 1992 May 1;89(9):4109-13. doi: 10.1073/pnas.89.9.4109.
We estimated whether single collections of cord blood contained sufficient cells for hematopoietic engraftment of adults by evaluating numbers of cord blood and adult bone marrow myeloid progenitor cells (MPCs) as detected in vitro with steel factor (SLF) and hematopoietic colony-stimulating factors (CSFs). SLF plus granulocyte-macrophage (GM)-CSF detected 8- to 11-fold more cord blood GM progenitors [colony-forming units (CFU)-GM] than cells stimulated with GM-CSF or 5637 conditioned medium (CM), growth factors previously used to estimate cord blood CFU-GM numbers. SLF plus erythropoietin (Epo) plus interleukin 3 (IL-3) enhanced detection of cord blood multipotential (CFU-GEMM) progenitors 15-fold compared to stimulation with Epo plus IL-3. Under the same conditions, bone marrow CFU-GM and CFU-GEMM were only enhanced in detection 2- to 4- and 6- to 8-fold. Increased detection of cord blood CFU-GEMM correlated directly with decreased detection of cord blood erythroid burst-forming units (BFU-E). In contrast, adult bone marrow CFU-GEMM and BFU-E numbers were both enhanced by SLF plus Epo plus IL-3. This suggests that most cord blood BFU-E may actually be CFU-GEMM. Cord blood collections (n = 17) contained numbers of MPCs (especially CFU-GM) similar to the number found in nine autologous bone marrow collections. To assess additional sources of MPCs, the peripheral blood of 1-day-old infants was assessed. However, average concentrations of MPCs circulating in these infants were only 30-46% that in their cord blood. Expansion of cord blood MPCs was also evaluated. Incubation of cord blood cells for 7 days with SLF resulted in 7.9-, 2.2-, and 2.7-fold increases in numbers of CFU-GM, BFU-E, and CFU-GEMM compared to starting numbers; addition of a CSF with SLF resulted in even greater expansion of MPCs. The results suggest that cord blood contains a larger number of early profile MPCs than previously recognized and that there are probably sufficient numbers of cells in a single cord blood collection to engraft an adult. Although the expansion data must be considered with caution, as human marrow repopulating cells cannot be assessed directly, in vitro expansion of cord blood stem and progenitor cells may be feasible for clinical transplantation.
我们通过评估在体外使用钢因子（SLF）和造血集落刺激因子（CSF）检测到的脐血和成人骨髓髓系祖细胞（MPC）数量，来估计单份脐血是否含有足够的细胞用于成人造血移植。与先前用于估计脐血CFU-GM数量的GM-CSF或5637条件培养基（CM）刺激的细胞相比，SLF加粒细胞-巨噬细胞（GM）-CSF检测到的脐血GM祖细胞[集落形成单位（CFU）-GM]多8至11倍。与Epo加IL-3刺激相比，SLF加促红细胞生成素（Epo）加白细胞介素3（IL-3）使脐血多能（CFU-GEMM）祖细胞的检测增强了15倍。在相同条件下，骨髓CFU-GM和CFU-GEMM的检测仅增强了2至4倍和6至8倍。脐血CFU-GEMM检测增加与脐血红系爆式集落形成单位（BFU-E）检测减少直接相关。相反，成人骨髓CFU-GEMM和BFU-E数量均因SLF加Epo加IL-3而增加。这表明大多数脐血BFU-E实际上可能是CFU-GEMM。脐血采集样本（n = 17）中MPC的数量（尤其是CFU-GM）与九份自体骨髓采集中发现的数量相似。为了评估MPC的其他来源，对1日龄婴儿的外周血进行了评估。然而，这些婴儿循环中的MPC平均浓度仅为其脐血中的30 - 46%。还评估了脐血MPC的扩增情况。与起始数量相比，脐血细胞与SLF孵育7天导致CFU-GM、BFU-E和CFU-GEMM数量分别增加了7.9倍、2.2倍和2.7倍；SLF添加一种CSF导致MPC扩增更大。结果表明，脐血中早期的MPC数量比之前认为的要多，并且单份脐血采集样本中可能有足够数量的细胞用于成人移植。尽管由于无法直接评估人类骨髓重建细胞，扩增数据必须谨慎考虑，但脐血干细胞和祖细胞的体外扩增对于临床移植可能是可行的。
