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Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth
Thesis (PhD (Medical Immunology))--University of Pretoria, 2024.
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| Format: | Thesis |
| Language: | English |
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University of Pretoria
2024
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| _version_ | 1867613514392141824 |
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| access_status_str | Open Access |
| author2 | Pepper, Michael Sean |
| author_browse | Pepper, Michael Sean |
| author_facet | Pepper, Michael Sean |
| collection | Thesis |
| dc_rights_str_mv | © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. |
| description | Thesis (PhD (Medical Immunology))--University of Pretoria, 2024. |
| format | Thesis |
| id | oai:repository.up.ac.za:2263/96862 |
| institution | University of Pretoria (South Africa) |
| language | English |
| last_indexed | 2026-06-10T12:37:21.635Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UPSpace — University of Pretoria Institutional Repository |
| publishDate | 2024 |
| publishDateRange | 2024 |
| publishDateSort | 2024 |
| publisher | University of Pretoria |
| publisherStr | University of Pretoria |
| record_format | dspace |
| source_str | UPSpace — University of Pretoria Institutional Repository |
| spelling | oai:repository.up.ac.za:2263/96862 Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth Pepper, Michael Sean candice_hendricks@outlook.com Mellet, Juanita Hendricks, Candice Laverne UCTD Haematopoietic stem cell transplantation Antiretroviral exposure HIV exposed uninfected infant HIV in transplantation Haematopoietic stem cells Umbilical cord blood expansion Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Health Sciences theses SDG-03 Thesis (PhD (Medical Immunology))--University of Pretoria, 2024. Umbilical cord blood (UCB) has been used for approximately 30 years as a source of haematopoietic stem and progenitor cells (HSPCs) for haematopoietic stem cell transplantation (HSCT). Advantages include less stringent allele matching requirements and lower immunogenicity compared to other stem cell (SC) sources. The greatest disadvantage is the lower HSPC number leading to slower haematopoietic recovery. This has led to its use primarily in paediatric patients who are able to benefit from the administration of one unit as opposed to two or more units as would be required in adults to achieve similar outcomes. Multiple in vitro HSPC expansion techniques have been used to overcome this barrier and have been shown to decrease time to engraftment. In South Africa (SA) however, many challenges exist in accessing HSCT, which include but are not limited to infrastructure, human resource barriers, SC donors and a high prevalence of human immunodeficiency virus (HIV). There is also no public UCB bank and thus UCB HSCT is rare. The HIV prevalence presents a major challenge as approximately 30-40% of expectant mothers are infected with HIV nationally. With a mother to child transmission (MTCT) rate of 1-2%, the vast majority of infants born to HIV positive mothers, and thus their UCB, are HIV negative. The impact of maternal HIV associated chronic immune activation and antiretroviral (ARV) exposure on the immunophenotype, expansion ability and function of UCB HSPCs from HIV exposed but uninfected infants (HEU infants), and similarities to or differences from HSPCs from HIV unexposed uninfected (HUU) infants, merits investigation. In this study, UCB HSPCs from HIV exposed infants born from virologically suppressed mothers, and who test HIV PCR negative at birth (HEU infants), were characterised by immunophenotype, differentiation capacity, expansion ability, and gene expression, and compared to an HIV negative control group. Immunophenotyping was performed by flow cytometry on freshly isolated CD34+ HSPCs to determine different CD34+ subsets. Expansion was performed using cytokines in the presence or absence of StemRegenin-1 (SR1), to determine the expansion ability of these cells. SR1 is a small-molecule aryl hydrocarbon receptor antagonist that causes an exponential increase in CD34+ HSPCs cultured in vitro. The optimal dose for expansion, as well as confirmation of an increase in the HSPC population, has been determined in our laboratory. Colony forming unit (CFU) assays were used as an indicator of differentiation capacity of freshly isolated CD34+ HSPCs, and the gene expression profile of unexpanded CD34+ cells was determined by microarray analysis. Additionally, the effect of ARVs, individually and in combinations as seen in maternal ARV fixed-drug combination (FDC) tablets, on UCB HSPCs from HUU infants, was determined by assessing impact on immunophenotype, expansion and differentiation capacity. This combined approach has been valuable in portraying differences between CD34+ cells from HEU infants compared to HUU infants, which may have implications for (a) the possible utility of HSPCs from these infants for HSCT, a currently unexplored area meriting research, and (b) the haematological profile of HEU infants. Netcare Physicians Partnership Trust, Professor Bongani Mayosi Clinical scholarship to the student South African Medical Research Council extramural unit for stem cell research and therapy to Prof MS Pepper University of Pretoria to Prof MS Pepper Immunology PhD (Medical Immunology) Restricted Faculty of Health Sciences 2024-07-09T12:38:20Z 2024-07-09T12:38:20Z 2024-09-03 2024-06 Thesis * S2024 http://hdl.handle.net/2263/96862 https://doi.org/10.25403/UPresearchdata.25921591.v3 en © 2023 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. application/pdf University of Pretoria |
| spellingShingle | UCTD Haematopoietic stem cell transplantation Antiretroviral exposure HIV exposed uninfected infant HIV in transplantation Haematopoietic stem cells Umbilical cord blood expansion Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Health Sciences theses SDG-03 Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth |
| title | Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth |
| title_full | Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth |
| title_fullStr | Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth |
| title_full_unstemmed | Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth |
| title_short | Characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from HIV exposed infants that are HIV negative at birth |
| title_sort | characterisation of umbilical cord blood derived haematopoietic stem and progenitor cells from hiv exposed infants that are hiv negative at birth |
| topic | UCTD Haematopoietic stem cell transplantation Antiretroviral exposure HIV exposed uninfected infant HIV in transplantation Haematopoietic stem cells Umbilical cord blood expansion Sustainable Development Goals (SDGs) SDG-03: Good health and well-being Health Sciences theses SDG-03 |
| url | http://hdl.handle.net/2263/96862 https://doi.org/10.25403/UPresearchdata.25921591.v3 |