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Development of an Allogeneic, Anti-Inflammatory Bone Marrow Stromal Cell Therapy for Chronic Low Back Pain Patients with Modic Type 1 Changes


Herger, Nick. Development of an Allogeneic, Anti-Inflammatory Bone Marrow Stromal Cell Therapy for Chronic Low Back Pain Patients with Modic Type 1 Changes. 2024, University of Zurich, Faculty of Science.

Abstract

Chronic low back pain is not only a prevalent but also an extremely disabling condition. Modic type 1 changes (MC1) – painful fibro-inflammatory changes in the vertebral bone marrow adjacent to degenerated intervertebral discs – are frequently observed in chronic low back pain (cLBP) patients. Yet, they are not considered a specific source of pain. Despite solid evidence supporting a clear association of MC1 with cLBP, patients suffering from cLBP receive the same treatment as cLBP patients without MC1. The high prevalence of cLBP patients with MC1, combined with the absence of a recognized treatment strategy, underscores the need for a targeted treatment. This doctoral dissertation, aimed to lay the foundation for the development of an allogeneic, anti inflammatory bone marrow mesenchymal stromal cell (MSC) therapy for cLBP patients with MC1. We identified that the painful inflammation – a pivotal pathologic feature of MC1 – could be targeted by the substantial anti-inflammatory properties of MSCs. We have discussed the advantages and disadvantages of using highly anti-inflammatory, allogeneic MSCs to treat MC1 in light of previous investigational MSC treatments for cLBP patients. Our literature review suggested that a high anti inflammatory potency of an MSC therapy is essential to achieve a beneficial therapeutic effect. Pro inflammatory and 3D culture priming demonstrated a considerable efficacy in enhancing the anti inflammatory potential of MSCs. We demonstrated, that continuous 3D culture was able to maintain the enhanced anti-inflammatory potential, supporting the administration of MSC spheroids for a sustainably improved anti-inflammatory potency. The achievements presented in this doctoral dissertation laid the foundation for the development of an allogeneic, anti-inflammatory bone marrow MSC therapy for cLBP patients with MC1. Future studies should focus on reducing the inconsistent potencies of MSC preparations.

Abstract

Chronic low back pain is not only a prevalent but also an extremely disabling condition. Modic type 1 changes (MC1) – painful fibro-inflammatory changes in the vertebral bone marrow adjacent to degenerated intervertebral discs – are frequently observed in chronic low back pain (cLBP) patients. Yet, they are not considered a specific source of pain. Despite solid evidence supporting a clear association of MC1 with cLBP, patients suffering from cLBP receive the same treatment as cLBP patients without MC1. The high prevalence of cLBP patients with MC1, combined with the absence of a recognized treatment strategy, underscores the need for a targeted treatment. This doctoral dissertation, aimed to lay the foundation for the development of an allogeneic, anti inflammatory bone marrow mesenchymal stromal cell (MSC) therapy for cLBP patients with MC1. We identified that the painful inflammation – a pivotal pathologic feature of MC1 – could be targeted by the substantial anti-inflammatory properties of MSCs. We have discussed the advantages and disadvantages of using highly anti-inflammatory, allogeneic MSCs to treat MC1 in light of previous investigational MSC treatments for cLBP patients. Our literature review suggested that a high anti inflammatory potency of an MSC therapy is essential to achieve a beneficial therapeutic effect. Pro inflammatory and 3D culture priming demonstrated a considerable efficacy in enhancing the anti inflammatory potential of MSCs. We demonstrated, that continuous 3D culture was able to maintain the enhanced anti-inflammatory potential, supporting the administration of MSC spheroids for a sustainably improved anti-inflammatory potency. The achievements presented in this doctoral dissertation laid the foundation for the development of an allogeneic, anti-inflammatory bone marrow MSC therapy for cLBP patients with MC1. Future studies should focus on reducing the inconsistent potencies of MSC preparations.

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Additional indexing

Item Type:Dissertation (cumulative)
Referees:Distler Oliver, Snedeker Jess, Sommer Lukas, Bogdanova Anna Yulievna, Dudli Stefan
Communities & Collections:05 Vetsuisse Faculty > Veterinärwissenschaftliches Institut > Department of Molecular Mechanisms of Disease
07 Faculty of Science > Department of Molecular Mechanisms of Disease

07 Faculty of Science > Institute of Molecular Life Sciences
UZH Dissertations
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Place of Publication:Zürich
Date:21 March 2024
Deposited On:21 Mar 2024 15:25
Last Modified:21 May 2024 20:47
Number of Pages:112
OA Status:Green
  • Content: Published Version
  • Language: English