Abstract
Umbilical cord blood (UCB) units provide an alternative source of human hematopoietic stem cells (HSCs) for patients who require allogeneic stem cell transplantation but lack a matched donor. However, the limited number of HSCs within each UCB unit remains a major challenge for their use in regenerative medicine and HSC transplantation in adults. Efficient expansion of human HSCs in ex vivo cultures initiated with CD34+ cells isolated from UCBs can overcome this limitation. The method described here utilizes a deacetylase inhibitor, valproic acid (VPA), to rapidly expand to a high degree the numbers of functional HSCs and committed progenitors (HPCs). The expanded HSCs are capable of establishing both short-term and long-term multilineage hematopoietic reconstitution. This highly reproducible and simple protocol can be also applied to expansion of both HSCs and HPCs from different sources including the bone marrow and peripheral blood.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Papa L, Djedaini M, Hoffman R (2019) Ex vivo HSC expansion challenges the paradigm of unidirectional human hematopoiesis. Ann N Y Acad Sci 1466:39. https://doi.org/10.1111/nyas.14133
Papa L, Zimran E, Djedaini M, Ge Y, Ozbek U, Sebra R, Sealfon SC, Hoffman R (2018) Ex vivo human HSC expansion requires coordination of cellular reprogramming with mitochondrial remodeling and p53 activation. Blood Adv 2(20):2766–2779. https://doi.org/10.1182/bloodadvances.2018024273
Chaurasia P, Gajzer DC, Schaniel C, D'Souza S, Hoffman R (2014) Epigenetic reprogramming induces the expansion of cord blood stem cells. J Clin Invest 124(6):2378–2395. https://doi.org/10.1172/JCI70313
Papa L, Djedaini M, Hoffman R (2019) Mitochondrial role in stemness and differentiation of hematopoietic stem cells. Stem Cells Int 2019:4067162. https://doi.org/10.1155/2019/4067162
Moussy A, Papili Gao N, Corre G, Poletti V, Majdoul S, Fenard D, Gunawan R, Stockholm D, Paldi A (2019) Constraints on human CD34+ cell fate due to Lentiviral vectors can be relieved by Valproic acid. Hum Gene Ther 30(8):1023–1034. https://doi.org/10.1089/hum.2019.009
Notta F, Doulatov S, Laurenti E, Poeppl A, Jurisica I, Dick JE (2011) Isolation of single human hematopoietic stem cells capable of long-term multilineage engraftment. Science 333(6039):218–221. https://doi.org/10.1126/science.1201219
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2021 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Papa, L., Djedaini, M., Kintali, M., Schaniel, C., Hoffman, R. (2021). Ex Vivo Expansion of Adult Hematopoietic Stem and Progenitor Cells with Valproic Acid. In: Cobaleda, C., Sánchez-GarcÃa, I. (eds) Leukemia Stem Cells. Methods in Molecular Biology, vol 2185. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0810-4_16
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0810-4_16
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0809-8
Online ISBN: 978-1-0716-0810-4
eBook Packages: Springer Protocols