1. Faculty of Medicine and Health
  2. School of Medicine
  3. Research groups
  4. Regenerative Medicine

Regenerative Medicine

  • Group summary: Working collaboratively with academia, the NHS and industry, we undertake basic and translational research into human skeletal and joint resident stem cells. With a focus on uncultured cells and their native niches, we are developing novel and cost effective therapies for osteoarthritis and orthopaedic trauma.

What we do

The Mesenchymal Stem Cell Group is one of the UK leading research teams investigating the biology of human mesenchymal stem cells (MSCs) in health and pathological conditions including osteoarthritis and bone fracture. The Leeds group were the first to purify rare MSCs from human bone marrow using a combination of magnetic beads and multiparameter cell sorting, and to discover MSCs in joint synovial fluid.

Aims and objectives

The group’s aim is to utilize the knowledge on the in vivo biology of MSCs in skeletal and joint tissues in order to develop novel cost-effective approaches for the treatment of the growing burden of musculoskeletal disease, particularly osteoarthritis and complex bone injury.

Our research

The discovery of synovial fluid MSCs lead the group to offer new insights into the potential role of these cells in the repair of cartilage in patients with osteoarthritis treated using knee joint distraction. Our research into the potential therapeutic use of these joint resident stem cells has enabled us to develop, patent and license a novel medical device to increase joint specific stem cells numbers during routine surgery, and has been taken forward into a clinical investigation in patients with cartilage defects. This approach could offer considerable advantages to the patient and the healthcare service provider by increasing the regenerative capacity of the joint during a single procedure. The group continues research in this area closely working with surgeons, clinicians, medical device companies and academic collaborators answering basic science and clinical questions in order to improve the treatment of joint diseases.

The group has recently developed a fast and simple assay suitable for intra-operative assessment of bone marrow MSC numbers for bone and cartilage regenerative applications. We have also developed new approaches for the characterisation of platelet-rich plasma (PRP), a source of autologous growth factors promoting MSC functionality. Conducting a pilot clinical trial (T-PAC), we are currently investigating the clinical value of autologous MSC/PRP combination in patients with closed tibial fractures, and correlating the administered number of MSCs with the healing outcomes. The group’s work has also demonstrated the advantages of natural materials (e.g. collagen) for scaffolds intended for signle-stage bone regeneration with bone marrow aspirates or concentrates. In collaboration with other national and international researchers, we are developing novel biomimetic materials for regeneration of critical-size bone defects.

Basic science research in the group  is centered on the study of physiological MSC responses in acute trauma and osteoarthritis in relation to time post-injury (trauma) and disease severity (osteoarthritis). We have shown that, in osteoarhtiris, endogenous MSC responses result in their inappropriate differentiation from cartilage to bone lineages. This work leads to novel strategies for biological and biomechanical stimulation of these MSCs in the affected joints. As part of its strategy the group are investigating the role of innate and adaptive immunity on regulating MSC activity, and the immunolomodulatory proporties of MSCs in vivo.

Key publications

Key recent publications

  1. Baboolal TG et al. (2018) A Novel Arthroscopic Technique for Intraoperative Mobilization of Synovial Mesenchymal Stem Cells. Americal Journal of Sports Medicine (in press).
     
  2. El-Sherbiny EM et al (2018).T cell immunomodulation by clinically used allogeneic human cancellous bone fragments: a potential novel immunotherapy tool. Sci Rep. 8:13535.
     
  3. El-Jawhari et al (2017). The CD45lowCD271high Cell Prevalence in Bone Marrow Samples May Provide a Useful Measurement of the Bone Marrow Quality for Cartilage and Bone Regeneration. JBJS Am, 99, 1305-1313.
     
  4. Campbell TM et al (2016) Mesenchymal Stem Cell Alterations in Bone Marrow Lesions in Patients With Hip Osteoarthritis. Arthritis and Rheumatology, 68, 1648-1659.
     
  5. Baboolal TG et al (2016) Synovial fluid hyaluronan mediates MSC Attachment to cartilage, a potential novel mechanism contributing to cartilage repair in osteoarthritis using knee joint distraction. Annals of the Rheumatic Diseases, 75, 908-915.
     
  6. Cuthbert RJ et al (2015) Examining the feasibility of clinical grade CD271+ enrichment of mesenchymal stromal cells for bone regeneration. PLoS ONE, 10 (3).

Original milestone publications

  1. Jones EA et al.(2004) Enumeration and phenotypic characterisation of synovial fluid multipotential mesenchymal progenitor cells in infammatory and degenerative arthritis.  Arthritis and Rheumatism;48;817-27.
     
  2. Jones EA et al. (2002)  Isolation and characterisation of mesenchymal progenitor cells.  Arthritis and Rheumatism:46: 334

Patents

  1. Baboolal et al. Orthopaedic Medical Device, University of LeedsPCT/GB2015/052554, WO 2016034888 A1 LPB/P210154GB, licenced by Xiros.
     
  2. McGonagle et al. Immunomodulation with Implantation of Cellular Allograft WO2017100339A1.

 

Who we are

People

Professor Dennis McGonagle

View our team members