The commentary “Unrelated Cord Blood as a Source of Stem Cells: Cryopreservation Damage Can Be Alleviated by Restoring Mitochondrial Function” by Norbert Claude Gorin, published in Blood Science (2025), highlights the groundbreaking work of Yaojin Huang and Tao Cheng from the Tianjin Institute of Health Science. Their study identifies mitochondrial dysfunction as a key mechanism behind the long-term deterioration of cryopreserved umbilical cord blood (UCB) and demonstrates that this damage can be reversed through sulforaphane (SF) treatment.Study Overview
The investigators compared fresh UCB samples with cryopreserved units stored for up to 19 years, examining hematopoietic stem and progenitor cell (HSPC) function and mitochondrial health. Single-cell transcriptomic profiling revealed significant alterations in cryopreserved samples, particularly within CD34⁺ HSPCs.
A notable finding was the expansion of mitochondria-high (mitohigh) HSPC populations after long-term storage. These cells displayed impaired differentiation—especially toward megakaryocytic lineages—as well as reduced clonogenic capacity and diminished engraftment potential. While T cells, NK cells, and CD3⁺/CD8⁺ lymphocytes maintained relatively stable function, CD34⁺ HSPCs exhibited mitochondrial swelling, decreased NAD⁺ levels, increased reactive oxygen species (ROS), and evidence of compromised respiratory chain activity.
Functional Consequences of Cryopreservation
Functional assays demonstrated a clear time-dependent decline in UCB potency. Colony-forming unit (CFU) assays showed reduced progenitor output within the first 5 years of storage, particularly affecting megakaryocyte and erythroid lineages. In NOG mouse transplantation models, both primary and secondary engraftment were significantly lower for cryopreserved UCB compared with fresh samples.
Clinical observations supported these findings. In a cohort of 171 UCB transplant recipients, hematopoietic reconstitution declined steadily in correlation with storage duration. Platelet recovery was especially impaired: platelets derived from long-stored UCB did not appear until around 7 weeks post-transplant, compared with approximately 3 weeks for fresh UCB. These results suggest that long-term cryopreservation disproportionately affects megakaryocyte-biased HSPCs.
Restoring Mitochondrial Function With Sulforaphane
A major breakthrough of the study was the discovery that sulforaphane—a natural antioxidant that reduces mitochondrial ROS—can reverse cryopreservation-induced damage. A 40-hour post-thaw incubation of cryopreserved UCB with SF significantly improved HSPC clonogenicity and restored CD45⁺ cell engraftment in mice to levels similar to fresh UCB.
Even more promising, UCB units pre-treated with SF before cryopreservation and stored for one year retained markedly better functional capacity at thawing. These results identify SF as a potent mitochondria-protective agent with direct translational potential for improving the viability of long-term banked cord blood.
Historical and Clinical Context
Gorin places these findings within the broader context of hematopoietic stem cell transplantation (HSCT). Since the first UCB transplants in Paris in 1989 and 1996, UCB has remained a critical stem cell source—especially in China, where public banks now store over one million units. Although UCB use has declined in Western countries due to delayed engraftment and higher nonrelapse mortality, it continues to fill essential gaps when matched sibling donors are unavailable.
Efforts to enhance UCB efficacy, such as double UCB transplantation and ex vivo expansion products like Omidubicel, have improved outcomes. The discovery that SF can restore mitochondrial health and HSPC potency adds a novel strategy to potentially extend UCB storage life and improve clinical performance, especially in adult recipients who require high stem cell doses.
Implications and Future Directions
The study exemplifies translational research spanning molecular, cellular, animal, and clinical levels. By identifying mitochondrial impairment as a reversible driver of cryopreservation injury, it provides a clear mechanistic basis for improving UCB graft quality. The next step is clinical translation through prospective trials evaluating SF-treated UCB units.
If validated, this approach could redefine cord blood banking practices by improving the long-term usability of stored units and supporting broader adoption of UCB transplantation worldwide.
Conclusion
Cryopreservation induces mitochondrial dysfunction that weakens the hematopoietic potential of UCB, but sulforaphane can restore stem cell function and improve engraftment. These findings bridge mitochondrial biology with clinical transplantation and offer a promising path to enhancing the effectiveness of cord blood as a stem cell source.
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