Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York.
Department of Genetics, Albert Einstein College of Medicine, Bronx, New York.
Curr Opin Hematol. 2022 Nov 1;29(6):317-326. doi: 10.1097/MOH.0000000000000732. Epub 2022 Aug 29.
The purpose of this review is to primarily discuss the unwarranted decline in the use of umbilical cord blood (UCB) as a source of donor hematopoietic stem cells (HSC) for hematopoietic cell transplantation (HCT) and the resulting important implications in addressing healthcare inequities, and secondly to highlight the incredible potential of UCB and related birthing tissues for the development of a broad range of therapies to treat human disease including but not limited to oncology, neurologic, cardiac, orthopedic and immunologic conditions.
When current best practices are followed, unrelated donor umbilical cord blood transplant (CBT) can provide superior quality of life-related survival compared to other allogeneic HSC donor sources (sibling, matched or mismatched unrelated, and haploidentical) through decreased risks of relapse and chronic graft vs. host disease. Current best practices include improved UCB donor selection criteria with consideration of higher resolution human leukocyte antigen (HLA) typing and CD34+ cell dose, availability of newer myeloablative but reduced toxicity conditioning regimens, and rigorous supportive care in the early posttransplant period with monitoring for known complications, especially related to viral and other infections that may require intervention. Emerging best practice may include the use of ex vivo expanded single-unit CBT rather than double-unit CBT (dCBT) or 'haplo-cord' transplant, and the incorporation of posttransplant cyclophosphamide as with haploidentical transplant and/or incorporation of novel posttransplant therapies to reduce the risk of relapse, such as NK cell adoptive transfer. Novel, non-HCT uses of UCB and birthing tissue include the production of UCB-derived immune effector cell therapies such as unmodified NK cells, chimeric antigen receptor-natural killer cells and immune T-cell populations, the isolation of mesenchymal stem cells for immune modulatory treatments and derivation of induced pluripotent stem cells haplobanks for regenerative medicine development and population studies to facilitate exploration of drug development through functional genomics.
The potential of allogeneic UCB for HCT and novel cell-based therapies is undervalued and underutilized. The inventory of high-quality UCB units available from public cord blood banks (CBB) should be expanding rather than contracting in order to address ongoing healthcare inequities and to maintain a valuable source of cellular starting material for cell and gene therapies and regenerative medicine approaches. The expertise in Good Manufacturing Practice-grade manufacturing provided by CBB should be supported to effectively partner with groups developing UCB for novel cell-based therapies.
本综述的主要目的是讨论脐带血（UCB）作为造血细胞移植（HCT）供者造血干细胞（HSC）来源的使用不当下降，并由此导致在解决医疗保健不公平问题方面的重要影响；其次是强调 UCB 和相关分娩组织在开发广泛的治疗人类疾病的疗法方面的令人难以置信的潜力，包括但不限于肿瘤学、神经学、心脏病学、矫形和免疫学疾病。
当遵循当前的最佳实践时，与其他异基因 HSC 供者来源（兄弟姐妹、匹配或不匹配的无关供者、半相合）相比，无关供者脐带血移植（CBT）可以通过降低复发和慢性移植物抗宿主病的风险，提供更高质量的与生活相关的生存。当前的最佳实践包括改进 UCB 供者选择标准，考虑更高分辨率的人类白细胞抗原（HLA）分型和 CD34+细胞剂量，提供更新的、骨髓清除但毒性降低的调理方案，以及在移植后早期进行严格的支持性护理，监测已知并发症，特别是与病毒和其他感染相关的并发症，这些并发症可能需要干预。新兴的最佳实践可能包括使用体外扩增的单个单位 CBT 而不是双单位 CBT（dCBT）或“半相合脐带”移植，以及在半相合移植中加入移植后环磷酰胺和/或加入新型移植后疗法以降低复发风险，例如 NK 细胞过继转移。UCB 和分娩组织的新型非 HCT 用途包括产生 UCB 衍生的免疫效应细胞疗法，如未经修饰的 NK 细胞、嵌合抗原受体-NK 细胞和免疫 T 细胞群体，分离间充质干细胞进行免疫调节治疗，以及衍生诱导多能干细胞单倍体库，用于再生医学发展和人群研究，以促进通过功能基因组学探索药物开发。
异基因 UCB 用于 HCT 和新型细胞疗法的潜力被低估和未充分利用。公共脐带血库（CBB）提供的高质量 UCB 单位库存应该扩大而不是缩小，以解决持续存在的医疗保健不公平问题，并为细胞和基因疗法以及再生医学方法保留有价值的细胞起始材料来源。CBB 提供的符合良好生产规范（GMP）级制造的专业知识应得到支持，以便与开发新型细胞疗法的 UCB 有效合作。
