Date of Award
5-2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Bioengineering
Committee Chair/Advisor
Jeremy Mercuri
Committee Member
Brian Booth
Committee Member
Jiro Nagatomi
Committee Member
William Richardson
Abstract
Intervertebral disc degeneration (IVDD) has become increasingly prevalent and is a common contributing factor to low back pain. There are currently no clinical treatment options for IVDD that alleviate the symptoms of IVDD while simultaneously promoting repair of IVD tissue. One treatment option being explored is intradiscal administration of mesenchymal stromal cells (MSCs). However, the microenvironment of the degenerating IVD places significant stress on both native IVD cells and implanted cells. There are several questions that need to be addressed which may help further inform the development of efficacious intradiscal MSC therapies for IVDD. These questions include: 1) Do MSCs derived from different tissue sources respond differently to IVDD-like pH? 2) Does paracrine signaling between MSCs and native nucleus pulposus cells (NPCs) impact their response to IVDD-like pH? The primary findings of this work were that IVDD-like pH negatively affects MSC survival, senescence, and effector function. Furthermore, MSCs derived from different tissue sources respond to low pH in different ways. Additionally, it was found that indirect coculture of MSCs with NPCs resulted in significantly increased MSC survival, matrix production, and an altered cytokine release profile compared to MSCs cultured alone. Finally, this work determined that ASICs are partially responsible for MSC sensing of their local pH as blocking these ion channels significantly increased MSC survival, metabolic activity, matrix production, and growth factor release while significantly decreasing inflammatory cytokine production. Taken together, this research can be used to inform strategies to increase the therapeutic efficacy of MSC-based intradiscal therapies targeting IVDD.
Recommended Citation
Cannon, Kyle, "Mesenchymal Stromal Cell Response to Degenerated Intervertebral Disc-Like PH" (2024). All Dissertations. 3568.
https://open.clemson.edu/all_dissertations/3568
Author ORCID Identifier
0009-0002-1812-3810