The influence of ECM on mesenchymal stromal/stem cell activity and their interactions with monocytes/macrophages
type: CreativeWork
description: Osteoarthritis is a prevalent degenerative condition affecting synovial joints, resulting in pain, stiffness, and difficulty with movement. Current treatments mainly alleviate symptoms without effectively regenerating the lost cartilage tissue. An early surgical intervention for focal cartilage damage, known as marrow stimulation or microfracture, aims to repair this damage by promoting endogenous healing. However, the resulting repair tissue often lacks the properties of native cartilage, raising questions about the long-term effectiveness of this approach. Therefore, to enhance the outcome of this osteochondral repair approach, it is necessary to understand the biological mechanisms involved in the healing process following microfracture. Osteochondral repair is a complex interplay of cellular interactions and changing extracellular matrix (ECM) environment. This thesis aimed to extend the current understanding of the biology underpinning this process, focusing on the interaction between mesenchymal stromal/stem cells (MSCs) and monocytes/macrophages within dynamically changing ECM proteins found at the injury site. We hypothesized that this interaction plays a pivotal role in determining the outcome of tissue repair. In our investigation, we first characterised the deposition and remodelling patterns of key ECM proteins, fibrin and collagen type 1, during osteochondral injury repair in C57BL/6 mice. Our findings revealed that fibrin was the predominant ECM protein in the initial seven days post-injury, which was subsequently gradually replaced by collagen type 1. At eight weeks post-injury, the tissue repair outcome at the articular surface was found to contain collagen type 1, perhaps representing an immature form of hyaline cartilage. Subsequent *in vitro* studies, using 3D ECM models constructed from fibrin and collagen type 1, demonstrated that these environments significantly modulate MSC morphology, proliferation, migration, and immunomodulatory activity. N…
abstract: Osteoarthritis is a prevalent degenerative condition affecting synovial joints, resulting in pain, stiffness, and difficulty with movement. Current treatments mainly alleviate symptoms without effectively regenerating the lost cartilage tissue. An early surgical intervention for focal cartilage damage, known as marrow stimulation or microfracture, aims to repair this damage by promoting endogenous healing. However, the resulting repair tissue often lacks the properties of native cartilage, raising questions about the long-term effectiveness of this approach. Therefore, to enhance the outcome of this osteochondral repair approach, it is necessary to understand the biological mechanisms involved in the healing process following microfracture. Osteochondral repair is a complex interplay of cellular interactions and changing extracellular matrix (ECM) environment. This thesis aimed to extend the current understanding of the biology underpinning this process, focusing on the interaction between mesenchymal stromal/stem cells (MSCs) and monocytes/macrophages within dynamically changing ECM proteins found at the injury site. We hypothesized that this interaction plays a pivotal role in determining the outcome of tissue repair. In our investigation, we first characterised the deposition and remodelling patterns of key ECM proteins, fibrin and collagen type 1, during osteochondral injury repair in C57BL/6 mice. Our findings revealed that fibrin was the predominant ECM protein in the initial seven days post-injury, which was subsequently gradually replaced by collagen type 1. At eight weeks post-injury, the tissue repair outcome at the articular surface was found to contain collagen type 1, perhaps representing an immature form of hyaline cartilage. Subsequent *in vitro* studies, using 3D ECM models constructed from fibrin and collagen type 1, demonstrated that these environments significantly modulate MSC morphology, proliferation, migration, and immunomodulatory activity. N…
author: Alkhrayef, Mohammad
language: eng
keywords: Extracellular matrix, macrophages, mesenchymal stromal/stem cells, monocytes, Osteoarthritis, osteochondral repair
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/5d6e8307-dfbd-42a4-a58a-86bf19cd826f/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-10-30
date modified: 2026-07-22T22:24:13Z
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.106706