Extensive immunophenotypic sub-population analysis of StemRegenin1 expanded haematopoietic stem/progenitor cells

dc.contributor.authorMellet, Juanita
dc.contributor.authorHendricks, Candice Laverne
dc.contributor.authorStivaktas, Voula
dc.contributor.authorDurandt, Chrisna
dc.contributor.authorAmbele, Melvin Anyasi
dc.contributor.authorPepper, Michael Sean
dc.contributor.emailmichael.pepper@up.ac.zaen_US
dc.date.accessioned2024-11-08T12:27:13Z
dc.date.available2024-11-08T12:27:13Z
dc.date.issued2024-09
dc.descriptionDATA AVAILABILITY : The flow cytometry data used and/or analysed during the current study are available from the corresponding author on request. The gene expression data used and analysed during the current study are available in the GEO repository [accession number GSE146810 in https://www.ncbi.nlm.nih.gov/geo/].en_US
dc.description.abstractBACKGROUND : Ex vivo haematopoietic stem/progenitor cell (HSPCs) expansion constitutes an important area of research, and has the potential to improve access to umbilical cord blood (UCB) as a source of stem cells for haematopoietic stem cell transplantation (HSCT). The ability to improve stem cell dose and thereby reduce delayed engraftment times, which has plagued the use of UCB as a stem cell source since inception, is a recognised advantage. The extent to which cluster of differentiation (CD)34 sub-populations are affected by expansion with StemRegenin1 (SR1), and whether a particular subtype may account for better engraftment than others, is currently unknown. The purpose of this study was to determine the impact of SR1-induced HSPC expansion on CD34+ immunophenotypic subsets and gene expression profiles. METHODS : UCB-derived CD34+ HSPCs were characterised before (D0) and after expansion (D7) with SR1 using an extensive immunophenotypic panel. In addition, gene expression was assessed and differentially expressed genes were categorised into biological processes. RESULTS : A dose-dependent increase in the number of CD34+ HSPCs was observed with SR1 treatment, and unbiased and extensive HSPC immunophenotyping proved to be a powerful tool in identifying unique sub-populations within the HSPC repertoire. In this regard, we found that SR1 promotes the emergence of HSPC subsets which may aid engraftment post expansion. In addition, we observed that SR1 has a minimal effect on the transcriptome of 7-day expanded CD34+ HSPCs when compared to cells expanded without SR1, with only two genes being downregulated in the former. CONCLUSION : This study revealed that SR1 selects for potentially novel immunophenotypic HSPC subsets post expansion and has a minimal effect on the transcriptome of 7-day expanded HSPCs when compared to vehicle controls. Whether these distinct immunophenotypic sub-populations possess greater engraftment capacity remains to be tested in animal models.en_US
dc.description.departmentImmunologyen_US
dc.description.departmentOral Pathology and Oral Biologyen_US
dc.description.librarianhj2024en_US
dc.description.sdgSDG-03:Good heatlh and well-beingen_US
dc.description.sponsorshipThe South African Medical Research Council Extramural Unit for Stem Cell Research and Therapy and in terms of the SAMRC’s Flagship Award Project [SAMRC-RFA-UFSP-01-2013/STEM CELLS] as well as the Institute for Cellular and Molecular Medicine of the University of Pretoria.en_US
dc.description.urihttp://stemcellres.biomedcentral.comen_US
dc.identifier.citationMellet, J., Hendricks, C.L., Stivaktas, V. et al. Extensive immunophenotypic sub-population analysis of StemRegenin1 expanded haematopoietic stem/progenitor cells. Stem Cell Research and Therapy 15, 317 (2024). https://doi.org/10.1186/s13287-024-03895-x.en_US
dc.identifier.issn1757-6512 (online)
dc.identifier.other10.1186/s13287-024-03895-x
dc.identifier.urihttp://hdl.handle.net/2263/98997
dc.language.isoenen_US
dc.publisherBMCen_US
dc.rights© The Author(s) 2024. Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.en_US
dc.subjectUmbilical cord blood (UCB)en_US
dc.subjectHaematopoietic stem cell transplantation (HSCT)en_US
dc.subjectStemRegenin1 (SR1)en_US
dc.subjectEx vivo expansionen_US
dc.subjectGene expression profilesen_US
dc.subjectHaematopoietic stem and progenitor cells (HSPCs)en_US
dc.subjectImmunophenotypeen_US
dc.subjectSDG-03: Good health and well-beingen_US
dc.titleExtensive immunophenotypic sub-population analysis of StemRegenin1 expanded haematopoietic stem/progenitor cellsen_US
dc.typeArticleen_US

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