The role of the bone marrow niche and G-CSF in osteochondral repair
type: CreativeWork
description: Osteoarthritis is a debilitating condition with an increasing global burden. Regenerative strategies to treat damaged articular cartilage aim to relieve pain and maintain joint function. Procedures for osteochondral repair, such as drilling or microfracture of the subchondral bone, are thought to restore cartilage by delivering bone marrow cells to the defect site. However, the specific identity or contribution of these cells to the repair process is not well understood. Mesenchymal stem/stromal cells are thought to contribute to tissue repair by either progenitor or trophic action. In the bone marrow niche mesenchymal stem/stromal cells (BMSCs) contribute to haematopoietic stem and progenitor cell (HSPC) maintenance and the dynamics of this are disrupted by osteochondral repair procedures. In addition, the bone marrow niche can be further manipulated by the HSPC mobilising agent granulocyte-colony stimulating factor (G-CSF). This cytokine has previously been shown to improve the repair of osteochondral tissues, however, the cellular mechanisms underlying this response are poorly described. This thesis investigates BMSC and HSPC interactions in bone and cartilage repair, and the mechanism by which G-CSF may act to improve repair outcomes. To look at BMSC–HSPC interactions a co-culture system was designed and then used to demonstrate that HSPCs inhibit the differentiation of BMSCs towards osteogenic and chondrogenic lineages. To explore the interaction and role of these cells in vivo during osteochondral repair, a mouse defect model was established. Defects were 729 (± 42.6) µm wide at the articular surface, occupied 41.6 (± 2.5) % of the width of the patella groove and penetrated 1205 (± 58.6) µm into the distal femur. The coefficient of variation (CV) for each parameter was below 6%. The area of injury demonstrated regenerated articular cartilage, an observation not previously described in the typically poor healing C57Bl/6 strain of mice. Further, cells known to r…
abstract: Osteoarthritis is a debilitating condition with an increasing global burden. Regenerative strategies to treat damaged articular cartilage aim to relieve pain and maintain joint function. Procedures for osteochondral repair, such as drilling or microfracture of the subchondral bone, are thought to restore cartilage by delivering bone marrow cells to the defect site. However, the specific identity or contribution of these cells to the repair process is not well understood. Mesenchymal stem/stromal cells are thought to contribute to tissue repair by either progenitor or trophic action. In the bone marrow niche mesenchymal stem/stromal cells (BMSCs) contribute to haematopoietic stem and progenitor cell (HSPC) maintenance and the dynamics of this are disrupted by osteochondral repair procedures. In addition, the bone marrow niche can be further manipulated by the HSPC mobilising agent granulocyte-colony stimulating factor (G-CSF). This cytokine has previously been shown to improve the repair of osteochondral tissues, however, the cellular mechanisms underlying this response are poorly described. This thesis investigates BMSC and HSPC interactions in bone and cartilage repair, and the mechanism by which G-CSF may act to improve repair outcomes. To look at BMSC–HSPC interactions a co-culture system was designed and then used to demonstrate that HSPCs inhibit the differentiation of BMSCs towards osteogenic and chondrogenic lineages. To explore the interaction and role of these cells in vivo during osteochondral repair, a mouse defect model was established. Defects were 729 (± 42.6) µm wide at the articular surface, occupied 41.6 (± 2.5) % of the width of the patella groove and penetrated 1205 (± 58.6) µm into the distal femur. The coefficient of variation (CV) for each parameter was below 6%. The area of injury demonstrated regenerated articular cartilage, an observation not previously described in the typically poor healing C57Bl/6 strain of mice. Further, cells known to r…
author: Beaton, Francesca Emily
language: en
keywords: Bone, Cartilage, Mesenchymal, Wound repair, Granulocyte, Niche, Osteoarthritis, Microfracture, G-CSF, Osteochondral
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/90d524d7-e913-4ad8-a3dc-52c8389d08e9/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2019-05-18
date modified: 2026-07-22T22:24:14Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.39459