Modelling the mesenchymal stem cell niche in vitro using magnetic nanoparticles

Lewis, Emily Elizabeth Louise (2016) Modelling the mesenchymal stem cell niche in vitro using magnetic nanoparticles. PhD thesis, University of Glasgow.

Abstract

Mesenchymal stem cells (MSCs) are multipotent stem cells residing within the bone marrow, with the ability to differentiate into cells of mesodermic origin (e.g. bone, cartilage and fat). These cells also possess extensive immunomodulatory and wound healing properties. Therefore, MSCs have multiple applications in the field of regenerative medicine. However, present day culturing techniques, encourage a loss of multipotency and limit the availability of true MSCs, for research and clinical use. A culturing technique, which is able to sustain multipotent and quiescent MSCs, is therefore required for future use.
MSCs reside within a unique microenvironment in the bone marrow, termed the niche, which protects and regulates stem cell homeostasis. The niche environment controls maintenance, proliferation and differentiation of the stem cells. Current research is focused on the creation of an in vitro niche model, to study the regulatory mechanisms, which govern stem cell fate. The majority of existing models use traditional two-dimensional (2D) techniques. However, stem cells cultured by this method are known to lose potency and spontaneously differentiate into undesired cell types. These issues are caused by 2D in vitro niche models lacking the complexity and the three-dimensional (3D) nature, of the native in vivo niche. Therefore, in the last few years, research has moved away from 2D models, towards creating 3D in vitro niche models.
This project aimed to develop a novel, bio-responsive in vitro 3D MSC niche model. The methodology adopted the use of magnetic nanoparticle loaded MSCs, which were levitated using an external magnetic field, to form multicellular spheroids which were subsequently located within a Type I collagen gel. The MSCs within the spheroid niche model exhibited native niche behaviour (retention of multipotency and quiescence). Furthermore, in the presence of a wound, the model accelerated the wound healing process. The MSCs directionally migrated out of the niche towards the wound site and start differentiating into the local resident cell type. Further investigation, identified IL-6 as a potential MSC migratory signal in this bio-response.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: mesenchymal stem cells, stem cell niche, 3D scaffolds, wound healing.
• Subjects: Q Science > QH Natural history > QH301 Biology
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Supervisor's Name: Berry, Dr. Catherine and Dalby, Prof. Matthew
• Date of Award: 2016
• Depositing User: Mrs Emily Elizabeth Louise Lewis
• Unique ID: glathesis:2016-7243
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 22 Apr 2016 07:44
• Last Modified: 05 May 2016 10:56
• URI: https://theses.gla.ac.uk/id/eprint/7243