Design and Implementation of a Feedback Control System for the Ex Vivo Expansion of Hematopoietic Stem Cells
Year: 2014
Type: dissertation
Abstract: Hematopoietic stem and progenitor cell (HSPC) transplantation provides a curative stem cell therapy for hematological pathologies. Umbilical cord blood (UCB) is an attractive source of these cells, and ex vivo expansion would make these cells available to more patients. This endeavor is challenged by the accumulation of endogenously produced signaling factors in vitro, limiting HSPC expansion. We hypothesized that regulating these factors in real time with a feedback control system would enhance expansion. We combined a novel protein quantification assay with a fed-batch bioreactor system to dilute soluble factors, reducing their impact and improving expansion. We developed a mathematical model to further investigate the impact of feedback control on HSPC culture, and used it to design a sophisticated control algorithm to maximize the volumetric efficiency of the fed-batch culture system. This use of feedback control for stem cell culture provides an important step towards a robust bioprocess for HSPC expansion.
Source: TSpace (University of Toronto)
Author: Julia Caldwell
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2735001904