Dr Andrew Hall

Osteoarthritis (OA) is a common debilitating disease of the moveable joints which leads to the loss of cartilage (the tough tissue at the ends of the bones). Very little is known about the early stages however our preliminary results suggest that subtle changes to the shape of cartilage cells (chondrocytes) might be a key step in the process. We are also developing a model using human femoral heads obtained from patients with femoral neck fracture (and obtained with Ethical permission and patient consent). We aim to use this model to test various methods for repairing damaged cartilage using mesenchymal stromal cells (MSCs).

Dr Andrew Hall

Reader

Hugh Robson Building

15 George Square

Edinburgh EH8 9XD

Contact details

 Work: +44 (0)131 650 3263

 Email: a.hall@ed.ac.uk

Personal profile

  • 2007 - present: Reader
  • 1998 - 2007: Senior Lecturer, University of Edinburgh
  • 1996 - 1998: Lecturer, University of Edinburgh (Wellcome Trust University Award 1996-2001)
  • 1992 - 1996: Wellcome Trust Senior Research Fellow, University Laboratory of Physiology, Oxford
  • 1986 - 1992: University Demonstrator, University Laboratory of Physiology, Oxford
  • Visiting Research Associate, University of Alberta, Edmonton
  • 1983 - 1986: Research Associate to Dr JC Ellory, Physiological Laboratory, Cambridge
  • 1981 - 1983: Research Associate Department of Physiology and Biophysics, University of Illinois

Research Theme

Research Areas

1. What is the role of articular chondrocytes in osteoarthritis?

Osteoarthritis (OA) is an increasingly common, painful and debilitating syndrome of human articular cartilage. It used to be thought that it arose from cartilage ‘wear-and-tear’, but there is increasing evidence that changes to the physiology of chondrocytes plays a key role, although the details are largely unclear.

Human chondrocytes are normally ellipsoidal/spheroidal in shape, but using confocal microscopy and our state-of-the-art imaging resource (see IMPACT imaging facility) which enables the visualisation of the fine details of living cells within their native environment, we have observed chondrocytes with remarkable cytoplasmic ‘processes’ extending for significant distances from the cell body (see Hall 2019; Figure 1). These are present even in non-degenerate cartilage, and preliminary work suggests their incidence increases markedly with the degree of OA.

Changes to chondrocyte shape (morphology) alter the type and mechanical properties of the extracellular matrix which the cells produce. Are these changes to morphology an early and preventable step in the development of OA? We are currently studying the physiology of in situ chondrocytes which exhibit normal or abnormal morphology, to try to determine what causes the changes in shape and hence matrix metabolism that characterise OA. We are also developing a three-dimensional culture system to study the factors involved in the regulation of chondrocyte morphology under more defined conditions.

Figure 1. The variety of morphologies of in situ human chondrocytes within human cartilage. (a) shows the typical spheroidal/elliptical appearance of ‘normal’ chondrocytes and (b-e) example of a morphologically-abnormal chondrocytes with (b) short or (c) long cytoplasmic processes, (d) increased cell volume (hypertrophic) or cell clustering (e). Images taken from grade 0 (non-degenerate) and grade 1 (mildly degenerate) cartilage – see Hall 2019 for details).
Figure 1. The variety of morphologies of in situ human chondrocytes within human cartilage. (a) shows the typical spheroidal/elliptical appearance of ‘normal’ chondrocytes and (b-e) examples of a morphologically-abnormal chondrocytes with (b) short or (c) long cytoplasmic processes, (d) increased cell volume (hypertrophic) or cell clustering (e). Images taken from grade 0 (non-degenerate) and grade 1 (mildly degenerate) cartilage – see Hall 2019 for details).

 

2. Can we repair damaged cartilage with mesenchymal stromal cells (MSCs)?

Damage to cartilage can occur during joint injury or more normally as a result of osteoarthritis (OA). However cartilage is not capable of repair and there is tremendous interest in developing cartilage repair models so that they can inform us how to mend cartilage in patients. We obtain fresh femoral heads from patients undergoing surgery for femoral neck fracture. In older people often following a fall, the femur breaks and the femoral head must be replaced with a new joint. Normally the femoral heads are discarded but through a highly productive collaboration with an Orthopaedic surgeon (Dr A. Amin, Edinburgh Orthopaedics) we can quickly obtain these femoral heads which normally have cartilage in excellent condition. Figure 2 shows how we can prepare a femoral head with sample ‘wells’ into which MSCs can be placed and the whole joint then cultured aseptically for weeks. We can then monitor the ability of the MSCs to ‘repair’ the wells (or other types of cartilage injury) with viable (load-bearing) cartilage.

Figure 2. A human femoral head with small circular ‘wells’ prepared in the cartilage into which MSCs are placed and then stimulated to generate new cartilage. (F indicates the fovea and the source of the foveal ligament. Scale bar is 25mm).
Figure 2. A human femoral head with small circular ‘wells’ prepared in the cartilage into which MSCs are placed and then stimulated to generate new cartilage. (F indicates the fovea and the source of the foveal ligament. Scale bar is 25mm).

Other areas of Research Interest

  • Iatrogenic injury during orthopaedic surgery and chondroprotection (Amin & Hall, 2020).
  • Septic arthritis - in particular the effects of toxins from Staphylococcus aureus on the viability of articular chondrocytes (Smith et al., 2013; Clement et al., 2022)
  • Chondrocyte hypertrophy in the mammalian growth plate – a role for membrane transporters? (Loqman et al., 2013).
  • Morphology and matrix metabolism by chondrocytes in strong and weak gel cultures, and on artificial membranes (Karim et al., 2016)
  • Regulation of [Ca2+]i and pHi by in situ chondrocytes (Simpkin et al., 2007).

Team members

  • Mr Mohammed Algarni (PhD student)
  • Mr Zaid Alturkistani (PhD student)
  • Mr Yousef Almajed (PhD student – second supervisor)
  • Mr Abdulaziz Alomiery (PhD student – second supervisor)
  • Ms Swati Shaji (MSc student)
  • Ms Aneta Luczak (Visiting Research worker)
  • Mr Nassai Herren (Visiting ERASMUS student – Karolinska Institutet, Sweden).

Collaborations

Publications (Since 2016)

Karim, A., Bajbouj, K., Shafarin, J., Qaisar, R., Hall, A.C., Hamad, M. (2022). Iron overload induces oxidative stress, cell cycle arrest and apoptosis in chondrocytes. Frontiers in Cell and Developmental Biology 10: 821014. https://doi.org/10.3389/fcell.2022.821014

Karim, A., Bajbouj, K., Qaisar, R., Hall, A.C., Hamad, M. (2022). The role of disrupted iron homeostasis in the development and progression of arthropathy. J. Orthop. Res. 40(6):1243- 250. https://doi.org/10.1002/jor.25323

Clement, R., Hall, A.C., Wong, S.J., Howie, S.E.M., Simpson, H.W. (2022). Septic arthritis in an in vivo murine model induced by Staphylococcus aureus; a comparison between actions of the Hla toxin and the host immune response. Bone & Jt. Research 11(9):669–678. https://doi.org/10.1302/2046-3758.119.BJR-2022-0016.R1

Styczynska-Soczka, K., Amin, A.K., Simpson, A.H.W., Hall, A.C. (2021). Optimization and validation of a human ex vivo femoral head model for preclinical cartilage research and regenerative therapies. Cartilage. Vol. 13 (Suppl 2) 386S–397S. https://doi.org/10.1177/1947603520934534

Styczynska-Soczka, K., Amin, A.K., & Hall, A.C. (2021). Cell-associated Type I collagen in non-degenerate and degenerate human articular cartilage. J. Cell. Physiology 236:7672–7681. https://doi.org/10.1002/jcp.30418

Miller, R.P., Berlouis, M.E., Hall, A.G., Smith, I.D.M., Simpson, A.H.R.W., & Hall, A.C. (2021). Effect of antibiotics on Staphylococcus aureus α-toxin levels: implications for the treatment of septic arthritis. Cartilage 12(3) 362–376 https://doi: 10.1177/1947603519828433

Almajed, Y.A., Hall, A.C., Gillingwater, T.H., Alashkham, A. (2021). Anatomical, functional and biomechanical review of the glenoid labrum. J. Anatomy  240(4):761-771. http://doi.org/10.1111/joa.13582

Liu, C.L.S. & Hall, A.C. (2020). Optimising the composition of irrigation fluid to reduce the potency of Staphylococcus aureus α -toxin: a possible role in the treatment of septic arthritis. Cartilage 11(4):500-511. https://doi.org/10.1177/1947603518798888

Howard, T.A., Murray, I.R., Amin, A.K., Simpson, A.H.R.W. & Hall, A.C. (2020). Damage control articular surgery: maintaining chondrocyte health and minimising iatrogenic injury. Injury 51(2) S83-S89.  https://doi.org/10.1016/j.injury.2019.10.072

Amin, A.K. & Hall, A.C. (2020). Raising the osmolarity of arthroscopic irrigating solutions may be chondroprotective: we must be kind to our joints during arthroscopy. Arthroscopy 36(12):3058-3060. https://doi.org/10.1016/j.arthro.2020.08.021

Hall, A.C. (2019). The role of chondrocyte morphology and volume in controlling phenotype – implications for osteoarthritis, cartilage repair and cartilage engineering. Curr. Top. Rheumatol.  21:38 https://doi.org/10.1007/s11926-019-0837-6

Karim, A., Amin, A.K. & Hall, A.C. (2018). The clustering and morphology of chondrocytes in normal and mildly-degenerate human femoral head cartilage studied by confocal laser scanning microscopy. J. Anatomy 232(4):686-698. doi: 10.1111/joa.12768.

Lin, Y-C., Hall, A.C., & Simpson, A.H.R.W. (2018). A novel joint organ culture model for evaluation of static and dynamic load on articular cartilage. Bone & Jt. Research 7(3): 205-212. doi: 10.1302/2046-3758.73BJR-2017-0320

Eltawil, N.M., Ahmed, S., Chan, L.H., Simpson, A.H.R.W. & Hall, A.C. (2018). Chondroprotection in a model of cartilage injury by raising the temperature and osmolarity of arthroscopic irrigation solutions. Cartilage 9(3) 313–320 https://doi.org/10.1177/1947603516688511

Smith, I.D.M., Milto, K.M., Doherty, C.J., Amyes, S.G.B., Simpson, A.H.R.W., & Hall, A.C. (2018). A potential key role of alpha-haemolysin of Staphylococcus aureus in mediating chondrocyte death in septic arthritis. Bone & Jt. Research 7(7): 457-467. https://doi: 10.1302/2046-3758.77.BJR-2017-0165.R1

Karim, A. & Hall, A.C. (2017). Chondrocyte morphology in stiff and soft agarose gels and the influence of fetal calf serum. J. Cell Physiology 232(5):1041-1052. https://doi.org/10.1002/jcp.25507

Amin, A.K., Simpson, A.H.R.W. & Hall, A.C. (2017). Iatrogenic articular cartilage injury: the elephant in the orthopaedic operating theatre. The surgeon’s role in chondroprotection. Bone & Jt. Journal (Editorial). 99(B)12:1555-6. doi: 10.1302/0301-620X.99B12.BJJ-2017-1337.

Lin, Y-C., Hall, A.C., Smith, I.D.M., Salter, D.M. & Simpson, A.H.R.W. (2016). Mapping chondrocyte viability, matrix glycosaminoglycan content, and water content on the surface of a bovine metatarsophalangeal joint. Cartilage 7(2):193-203.

Karim, A., & Hall, A.C. (2016). Hyperosmolarity normalizes serum-induced changes to chondrocyte properties in a model of cartilage injury. Europ. Cells & Mat. 31:205-220. DOI:10.22203/ecm.v031a14 

Paterson, S.I., Eltawil, N.M., Simpson, A.H.R.W., Amin, A.K. & Hall, A.C. (2016). Drying of open animal joints in vivo subsequently causes cartilage degeneration. Bone Jt. Res. 5:137-144. https://doi.org/10.1302/2046-3758.54.2000594

 

 

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