Lundell B I, Vredenburgh J J, Tyer C, DeSombre K, Smith A K
Aastrom Biosciences, Ann Arbor, MI 48105, USA.
Bone Marrow Transplant. 1998 Jul;22(2):153-9. doi: 10.1038/sj.bmt.1701314.
High-dose chemotherapy (HDC) with hematopoietic support appears promising in the treatment of breast cancer, although reinfusion of contaminating tumor cells may contribute to disease relapse. Ex vivo expansion may reduce tumor cell content through use of a small inoculum volume and by passive purging during culture. We assessed the ex vivo expansion potential of tumor cell positive bone marrow (BM) from breast cancer patients and the effect of ex vivo expansion on tumor cell content. Cryopreserved/thawed mononuclear cell (C/T MNC) BM harvests with known tumor cell contamination (n = 7) were assessed for tumor cells pre- and post-expansion using immunocytochemical (ICC) staining. Pre-expansion inoculum samples contained a range of 6-2128 tumor cells per 5.0 x 10(6) nucleated cells. Ex vivo expansion resulted in fold expansions of 6.67 and 11.37 for total cells and CFU-GM, respectively. Tumor cells were undetectable in four of the seven post-expansion samples and were reduced in the remaining three samples. The data demonstrate passive purging of breast cancer cells during ex vivo expansion, with hematopoietic progenitor cell expansion comparable to that of normal BM. Reduction in tumor cell number contained in the small volume culture inoculum combined with passive purging during the ex vivo expansion process suggest a potential 2-4+ log reduction in tumor cell content in the reinfused cell product.
尽管回输受污染的肿瘤细胞可能导致疾病复发，但高剂量化疗（HDC）联合造血支持在乳腺癌治疗中似乎很有前景。体外扩增可通过使用小接种量以及在培养过程中进行被动清除来降低肿瘤细胞含量。我们评估了乳腺癌患者肿瘤细胞阳性骨髓（BM）的体外扩增潜力以及体外扩增对肿瘤细胞含量的影响。使用免疫细胞化学（ICC）染色对已知肿瘤细胞污染情况（n = 7）的冷冻保存/解冻单核细胞（C/T MNC）骨髓采集物在扩增前后进行肿瘤细胞评估。扩增前接种物样本每5.0×10⁶有核细胞中含有6 - 2128个肿瘤细胞。体外扩增使总细胞和CFU - GM分别扩增了6.67倍和11.37倍。在七个扩增后样本中的四个样本中未检测到肿瘤细胞，其余三个样本中的肿瘤细胞减少。数据表明在体外扩增过程中乳腺癌细胞被被动清除，造血祖细胞的扩增与正常骨髓相当。小体积培养接种物中所含肿瘤细胞数量的减少以及体外扩增过程中的被动清除表明，回输细胞产品中的肿瘤细胞含量可能有2 - 4个对数级以上的降低。
