Bari Sudipto, Seah Kevin Kwee Hong, Poon Zhiyong, Cheung Alice Man Sze, Fan Xiubo, Ong Shin-Yeu, Li Shang, Koh Liang Piu, Hwang William Ying Khee
Department of Hematology, Singapore General Hospital, Singapore; Department of Pharmacy, National University of Singapore, Singapore.
Sydney Medical School, The University of Sydney, Australia.
Biol Blood Marrow Transplant. 2015 Jun;21(6):1008-19. doi: 10.1016/j.bbmt.2014.12.022. Epub 2014 Dec 30.
The successful expansion of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (UCB) for transplantation could revolutionize clinical practice by improving transplantation-related outcomes and making available UCB units that have suboptimal cell doses for transplantation. New cytokine combinations appear able to promote HSPC growth with minimal differentiation into mature precursors and new agents, such as insulin-like growth factor-binding protein 2, are being used in clinical trials. Molecules that simulate the HSPC niche, such as Notch ligand, have also shown promise. Further improvements have been made with the use of mesenchymal stromal cells, which have made possible UCB expansion without a potentially deleterious prior CD34/CD133 cell selection step. Chemical molecules, such as copper chelators, nicotinamide, and aryl hydrocarbon antagonists, have shown excellent outcomes in clinical studies. The use of bioreactors could further add to HSPC studies in future. Drugs that could improve HSPC homing also appear to have potential in improving engraftment times in UCB transplantation. Technologies to expand HSPC from UCB and to enhance the homing of these cells appear to have attained the goal of accelerating hematopoietic recovery. Further discoveries and clinical studies are likely to make the goal of true HSPC expansion a reality for many applications in future.
从脐带血（UCB）中成功扩增造血干细胞和祖细胞（HSPCs）用于移植，可能会通过改善移植相关结果并使细胞剂量次优的UCB单位可供移植，从而彻底改变临床实践。新的细胞因子组合似乎能够促进HSPC生长，同时将分化为成熟前体的情况降至最低，并且诸如胰岛素样生长因子结合蛋白2等新型药物正在临床试验中使用。模拟HSPC生态位的分子，如Notch配体，也已显示出前景。使用间充质基质细胞已取得进一步进展，这使得在无需进行潜在有害的预先CD34/CD133细胞选择步骤的情况下实现UCB扩增成为可能。化学分子，如铜螯合剂、烟酰胺和芳烃拮抗剂，在临床研究中已显示出优异的结果。生物反应器的使用可能会在未来进一步推动HSPC研究。能够改善HSPC归巢的药物似乎在缩短UCB移植中的植入时间方面也具有潜力。从UCB中扩增HSPC并增强这些细胞归巢的技术似乎已经实现了加速造血恢复的目标。未来进一步的发现和临床研究可能会使真正的HSPC扩增目标在许多应用中成为现实。
