Hornberger Kathlyn, Yu Guanglin, McKenna David, Hubel Allison
Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Department of Mechanical Engineering, University of Minnesota, Minneapolis, Minnesota, USA.
Transfus Med Hemother. 2019 Jun;46(3):188-196. doi: 10.1159/000496068. Epub 2019 Feb 5.
Hematopoietic stem cell (HSC) therapy is widely used to treat a growing number of hematological and non-hematological diseases. Cryopreservation of HSCs allows for cells to be transported from the site of processing to the site of clinical use, creates a larger window of time in which cells can be administered to patients, and allows sufficient time for quality control and regulatory testing. Currently, HSCs and other cell therapies conform to the same cryopreservation techniques as cells used for research purposes: cells are cryopreserved in dimethyl sulfoxide (DMSO) at a slow cooling rate. As a result, HSC therapy can result in numerous adverse symptoms in patients due to the infusion of DMSO. Efforts are being made to improve the cryopreservation of HSCs for clinical use. This review discusses advances in the cryopreservation of HSCs from 2007 to the present. The preclinical development of new cryoprotectants and new technology to eliminate cryoprotectants after thawing are discussed in detail. Additional cryopreservation considerations are included, such as cooling rate, storage temperature, and cell concentration. Preclinical cell assessment and quality control are discussed, as well as clinical studies from the past decade that focus on new cryopreservation protocols to improve patient outcomes.
造血干细胞(HSC)疗法被广泛用于治疗越来越多的血液系统疾病和非血液系统疾病。造血干细胞的冷冻保存使得细胞能够从处理地点运输到临床使用地点,为细胞给药给患者创造了更大的时间窗口,并为质量控制和监管测试留出了足够的时间。目前,造血干细胞和其他细胞疗法采用与用于研究目的的细胞相同的冷冻保存技术:细胞在二甲基亚砜(DMSO)中以缓慢的冷却速率进行冷冻保存。因此,由于输注二甲基亚砜,造血干细胞疗法可能会在患者身上导致许多不良症状。目前正在努力改进用于临床的造血干细胞的冷冻保存方法。这篇综述讨论了2007年至今造血干细胞冷冻保存方面的进展。详细讨论了新型冷冻保护剂的临床前开发以及解冻后消除冷冻保护剂的新技术。还包括其他冷冻保存方面的考虑因素,如冷却速率、储存温度和细胞浓度。讨论了临床前细胞评估和质量控制,以及过去十年中关注新的冷冻保存方案以改善患者预后的临床研究。