UM171 Expansion of Cord Blood Improves Donor Availability and HLA Matching For All Patients, Including Minorities

Dumont-Lagacé, Maude; Feghaly, Albert; Meunier, Marie-Christine; Finney, Marcie; Hof, Wouter van’t; Frenet, Emeline Masson; Sauvageau, Guy; Cohen, Sandra

doi:10.1016/j.jtct.2022.03.016

Cited by 10 publications

(11 citation statements)

References 23 publications

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“…It has also been suggested that this expansion technique could benefit racial and ethnic minorities who often face challenges in finding suitable donors. 37 Two phase II trials (NCT03913026 and NCT04103879) are currently underway for high-risk acute leukemia and myelodysplastic syndrome, evaluating treatment-related mortality and relapse-free survival.…”

Section: Days)mentioning

confidence: 99%

“…In addition, calculations using data from US CB banks showed that the donor availability for all patients increased from 72% to 84% with this expansion technology. It has also been suggested that this expansion technique could benefit racial and ethnic minorities who often face challenges in finding suitable donors 37 . Two phase II trials (NCT03913026 and NCT04103879) are currently underway for high‐risk acute leukemia and myelodysplastic syndrome, evaluating treatment‐related mortality and relapse‐free survival.…”

Section: Clinical Trialsmentioning

confidence: 99%

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Ex vivo expansion of human hematopoietic stem cells and clinical applications

Sakurai,

Ishitsuka,

Becker

et al. 2024

Cancer Science

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Hematopoietic stem cells (HSCs) are a rare population of cells found in the bone marrow that play a critical role in lifelong hematopoiesis and the reconstitution of the hematopoietic system after hematopoietic stem cell transplantation. Hematopoietic stem cell transplantation remains the only curative treatment for patients with refractory hematologic disorders, and umbilical cord blood (CB) serves as an alternative stem cell source due to its several advantageous characteristics, including human leukocyte antigen flexibility and reduced donor burden. However, CB also has the disadvantage of containing a small number of cells, resulting in limited donor selection and a longer time for engraftment. Therefore, the development of techniques to expand HSCs ex vivo, particularly umbilical CB, is a goal in hematology. While various combinations of cytokines were once the mainstream approach, these protocols had limited expansion rates and did not lead to clinical application. However, in recent years, the development of a technique in which small molecules are added to cytokines has enabled the stable, long‐term ex vivo expansion of human HSCs. Clinical trials of expanded umbilical CB using these techniques have been undertaken and have confirmed their efficacy and safety. In addition, we have successfully developed a recombinant‐cytokine‐free and albumin‐free culture system for the long‐term expansion of human HSCs. This approach could offer the potential for more selective expansion of human HSCs compared to previous protocols. This review discusses ex vivo culture protocols for expanding human HSCs and presents the results of clinical trials using these techniques, along with future perspectives.

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Section: Days)mentioning

confidence: 99%

Section: Clinical Trialsmentioning

confidence: 99%

Ex vivo expansion of human hematopoietic stem cells and clinical applications

Sakurai,

Ishitsuka,

Becker

et al. 2024

Cancer Science

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“…The accessibility of umbilical cord blood (UCB) as a source of human HSCs has fuelled the development of ex-vivo expansion techniques to increase the yield of these rare cell types for further downstream therapeutic applications. Methods for expanding CD34 + cells from UCB, including treatment with UM171, a small molecule HSC self-renewal agonist, have shown a median 49-fold expansion of CD34 + cells and promising clinical outcomes (Cohen et al, 2020;Dumont-Lagacé et al, 2022). The limitations of these methods, however, are the inherent variability in quality of HSCs expanded in culture.…”

Section: Box 1 State Of the Art: Expansion Of Human Hscsmentioning

confidence: 99%

Markers for human haematopoietic stem cells: The disconnect between an identification marker and its function

Rix

Maduro²,

Bridge³

et al. 2022

Front. Physiol.

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The haematopoietic system is a classical stem cell hierarchy that maintains all the blood cells in the body. Haematopoietic stem cells (HSCs) are rare, highly potent cells that reside at the apex of this hierarchy and are historically some of the most well studied stem cells in humans and laboratory models, with haematopoiesis being the original system to define functional cell types by cell surface markers. Whilst it is possible to isolate HSCs to near purity, we know very little about the functional activity of markers to purify HSCs. This review will focus on the historical efforts to purify HSCs in humans based on cell surface markers, their putative functions and recent advances in finding functional markers on HSCs.

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“… 37 Importantly, the UM171 expansion markedly improved the usability of CB units stocked in CB banks, allowing the use of smaller CB units for transplantation purposes. 38 …”

Section: Hematopoiesis Hematopoietic Stem Cells and Agingmentioning

confidence: 99%

“…37 Importantly, the UM171 expansion markedly improved the usability of CB units stocked in CB banks, allowing the use of smaller CB units for transplantation purposes. 38 HSC differentiation. Hematopoiesis is a finely regulated process of cell differentiation through which HSCs generate blood elements of all hematopoietic lineages belonging to myeloid and lymphoid lineages.…”

Section: Hematopoiesis Hematopoietic Stem Cells and Agingmentioning

confidence: 99%

Clonal Hematopoiesis: Role in Hematologic Non-Hematologic

Testa¹,

Castelli²

2022

Mediterr J Hematol Infect Dis

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Hematopoietic stem cells (HSCs) ensure the coordinated and balanced production of all hematopoietic cell types throughout life. Aging is associated with a gradual decline of the self-renewal and regenerative potential of HSCs and with the development of clonal hematopoiesis. Clonal hematopoiesis of indeterminate potential (CHIP) is a term defining the clonal expansion of genetically variant hematopoietic cells bearing one or more gene mutations and/or structural variants (such as copy number alterations). CHIP increases exponentially with age and is associated with cancers, including hematologic neoplasia, cardiovascular and other diseases. The presence of CHIP consistently increases the risk of hematologic malignancy, particularly in individuals who have CHIP in association with peripheral blood cytopenia. Key words: hematopoiesis, hematopoietic stem cells, clonal hematopoiesis, gene mutations, next generation sequencing.

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UM171 Expansion of Cord Blood Improves Donor Availability and HLA Matching For All Patients, Including Minorities

Cited by 10 publications

References 23 publications

Ex vivo expansion of human hematopoietic stem cells and clinical applications

Ex vivo expansion of human hematopoietic stem cells and clinical applications

Markers for human haematopoietic stem cells: The disconnect between an identification marker and its function

Clonal Hematopoiesis: Role in Hematologic Non-Hematologic

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