Clinically compatible advances in blood-derived endothelial progenitor cell isolation and reprogramming for translational applications

Eminli, Sarah, Kwieder, Baraa, Yi, Kevin, Huang, Christopher J. Z., Moon, Jung Il, Chang, C. Hong, Kiskin, Fedir N., Morrell, Nicholas W., Hamilton, Brad and Rana, Amer A. ORCID: https://orcid.org/0000-0002-2330-4643 (2021) Clinically compatible advances in blood-derived endothelial progenitor cell isolation and reprogramming for translational applications. New Biotechnology, 63. pp. 1-9. ISSN 1871-6784

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Abstract

The promise of using induced pluripotent stem cells (iPSCs) for cellular therapies has been hampered by the lack of easily isolatable and well characterized source cells whose genomes have undergone minimal changes during their processing. Blood-derived late-outgrowth endothelial progenitor cells (EPCs) are used for disease modeling and have potential therapeutic uses including cell transplantation and the translation of induced pluripotent stem cell (iPSC) derivatives. However, the current isolation of EPCs has been inconsistent and requires at least 40−80 mL of blood, limiting their wider use. In addition, previous EPC reprogramming methods precluded the translation of EPC-derived iPSCs to the clinic. Here a series of clinically-compatible advances in the isolation and reprogramming of EPCs is presented, including a reduction of blood sampling volumes to 10 mL and use of highly efficient RNA-based reprogramming methods together with autologous human serum, resulting in clinically relevant iPSCs carrying minimal copy number variations (CNVs) compared to their parent line.

Item Type: Article
Additional Information: Funding Information: This research was funded by the British Heart Foundation (BHF) (project grant PG/14/31/30786 and programme grant RG/13/4/30107), the Cambridge National Institute for Health Research Biomedical Research Centre , the Dinosaur Trust , Foundation Leducq, Pulmonary Hypertension Association UK , Fight for Sight and the Robert McAlpine Foundation . NWM was supported by a BHF Chair Award ( CH/09/001/25945 ) and FNK was supported by a BHF PhD studentship ( FS/13/51/30636 ) and a travel grant from St Catharine’s College Cambridge . AAR and NWM would also like to acknowledge support from the BHF Centre of Regenerative Medicine, Oxford and Cambridge ( RM/13/3/30159 ), the BHF Centre for Research Excellence ( RE/13/6/30180 ), who also funded BK, BHF project grant PG/14/31/30786, the BHF IPAH cohort grant (SP/12/12/29836) and a Pfizer European Young Researcher of the Year award to AAR. Funding Information: This research was funded by the British Heart Foundation (BHF) (project grant PG/14/31/30786 and programme grant RG/13/4/30107), the Cambridge National Institute for Health Research Biomedical Research Centre, the Dinosaur Trust, Foundation Leducq, Pulmonary Hypertension Association UK, Fight for Sight and the Robert McAlpine Foundation. NWM was supported by a BHF Chair Award (CH/09/001/25945) and FNK was supported by a BHF PhD studentship (FS/13/51/30636) and a travel grant from St Catharine's College Cambridge. AAR and NWM would also like to acknowledge support from the BHF Centre of Regenerative Medicine, Oxford and Cambridge (RM/13/3/30159), the BHF Centre for Research Excellence (RE/13/6/30180), who also funded BK, BHF project grant PG/14/31/30786, the BHF IPAH cohort grant (SP/12/12/29836) and a Pfizer European Young Researcher of the Year award to AAR. Publisher Copyright: © 2021 Elsevier B.V.
Uncontrolled Keywords: clinical translation,epc,ipsc,reprogramming,self-replicating mrna,biotechnology,bioengineering,molecular biology,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1300/1305
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 03 Nov 2022 10:30
Last Modified: 14 Jun 2023 14:11
URI: https://ueaeprints.uea.ac.uk/id/eprint/89542
DOI: 10.1016/j.nbt.2021.02.001

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