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Towards the development of standardized potency assays in regenerative medicine bioprocessing for the treatment of ischemic cardiac injury

Abukar, FS; (2018) Towards the development of standardized potency assays in regenerative medicine bioprocessing for the treatment of ischemic cardiac injury. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The mechanisms by which mesenchymal cells can repair the infarcted myocardium are still unclear and are made more challenging by the fact that hMSCs engraft in the myocardium for only a short amount of time. This thesis first examined the ability of commercial bone marrow (BM) MSCs expanded in low serum (<5% FBS medium), umbilical cord (UC) MSCs and individual donor BM-MSCs to perform biologically relevant functions. The characterization studies showed that the differently-sourced hMSCs successfully underwent tri-lineage differentiation and displayed similar expression levels of positive MSC markers. Additionally to this, there was a tendency for cells at increased in vitro age to display reduced expression of CD105. Biologic priming of cells using sJag1 typically enhanced MSC attachment to fibronectin, although to varying degrees in the different MSC types. In addition, vascular support assays revealed that MSCs displayed pericyte-like behaviour lining the outside of the vessels and bridging in between endothelial cells during network formation. Assessment of how bioprocess parameters affect vascular tubule formation revealed that economic benefits can be derived by using lower volumes of alternative matrix substrates. In addition, automated counting tools achieved an unbiased measurement compared to manual counting processes. Finally, from a perspective of the vascular endothelial cells used in the assays, it was possible to extend their use an additional 50%, from passage 10 to passage 15 before losing functional capacity. With further work, these assays could be optimized for high-throughput screening and be used in industry as surrogate tests for quality control (QC) hence enabling the advancement of well-characterized cell therapy products.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Towards the development of standardized potency assays in regenerative medicine bioprocessing for the treatment of ischemic cardiac injury
Event: UCL (University College London)
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Chemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10047186
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