3085 – BROCCOLI EXTRACT MITIGATES CRYOPRESERVATION-INDUCED MITOCHONDRIAL DYSREGULATION IN CORD BLOOD CELLS

• Published in: Experimental hematology 2024-08, Vol.137, p.104407, Article 104407
• Main Authors: huang, Yaojin, Xie, Xiaowei, Liu, Mengyao, Zhang, Yawen, Dong, Fang, Zhang, Yingchi, Cheng, Tao
• Format: Article
• Language: English
• ISSN: 0301-472X
• DOI: 10.1016/j.exphem.2024.104407

Umbilical cord blood (UCB) showcases substantial roles in hematopoietic stem cells (HSCs) transplantation and regenerative medicine. UCB is usually cryopreserved for many years before being used. Whether and how cryopreservation affects the function of UCB remain to be defined. We first constructed a single-cell transcriptomic profile of CD34+ hematopoietic stem and progenitor cells (HSPCs) and mononuclear cells (MNCs) collected from fresh and cryopreserved UCB stored for 1-, 5-, 10-, and 19- years. Compared with the fresh group, hematopoietic stem cell and multipotent progenitor (HSC/MPP) after cryopreservation exhibited more active cell cycle and lower expression of HSC/MPP signature genes. Consistently, in vivo hematopoietic reconstitution of HSPCs derived from cryopreserved UCB gradually decreased during the first 5 years but remained relatively stable thereafter, which was mirrored by the negative correlation between neutrophil engraftment and cryopreservation duration of UCB in clinical transplantation patients. In addition, we observed a decreased megakaryocyte generation for cryopreserved HSPCs. In contrast, natural killer (NK) cells and T cells in the cryopreserved groups were comparable to those from the fresh group, as indicated by their cytokine production and cytotoxic ability. These effects could be ameliorated by the interference of broccoli extract. Together, we elucidated the negative impact of cryopreservation on UCB HSPCs and provided a mitigation strategy. Little damage of cryopreservation to NK and T cells had implications for UCB-based immune therapy. Our findings broaden the temporal window and scope for the clinical application of cryopreserved UCB.