NIHR Leeds BRC: Pre-clinical evaluation of novel regenerative medicine strategies for knee osteoarthritis


   Faculty of Medicine and Health

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  Prof Hemant Pandit, Prof D McGonagle  No more applications being accepted  Competition Funded PhD Project (UK Students Only)

About the Project

Historically, articular cartilage was considered incapable of spontaneous repair.  However, biomechanical correction in osteoarthritis (OA) using high tibial osteotomy or joint distraction demonstrated the remarkable joint to regeneration by “merely” correcting joint alignment. Work done in Leeds has offered novel insights into such repair responses. Basically, Leeds researchers undertook the original studies that identified the native phenotype of subchondral bone marrow mesenchymal stem cells (MSCs), the subchondral bone a key site in OA pathogenesis (Jones EA 2002). Subsequently the Leeds group discovered synovial fluid resident MSCs and later showed that such cells were elevated in the early stages of OA (Jones et al A&R 2004 and A&R 2008). Finally, in collaboration with the Dutch group that pioneered knee joint distraction (KJD) the Leeds group showed that synovial fluid resident MSCs actually integrated into superficial injured cartilage and hence we defined a hitherto unappreciated stem cell compartment relevant to joint regeneration (Baboolal T et al ARD 2015). 

Hypothesis:

An array of therapies is currently undergoing evaluation in OA including platelet rich plasma, fibroblast growth factors and wnt pathway modulators and others. An integrated body of work will be undertaken to evaluate novel molecules that stimulate joint fluid MSCs with measurement of chondrogenic differentiation responses. This will set the scene for combined joint biomechanical correction and novel molecular methods towards native MSCs stimulation towards joint repair. 

Methods

The proposed PhD will apply our knowledge of rare MSC isolation, MSC culture and trilineage differentiation assays, clonal assays of MSCs and bulk and single cell RNA sequencing and high sensitivity protein assays to define molecules that may optimally promote MSC proliferation and chondrogenic differentiation. This will inform novel strategies combining surgical correction methods and stem cell therapeutic agents.  

Entry Requirements and How to Apply

For more details about this project and how to apply please visit our website.

If you would like further information after visiting our website please contact Professor Sven Plein for project specific queries

e: [Email Address Removed]

or the Faculty Admissions Team for help with the application process

e: [Email Address Removed]

To support the application process or if you want to know more about our non-clinical PhDs a recording of our 2023 webinar can be found via the links below

**The deadline dates in the webinar are out of date but are correct in the stand-alone slide deck**

NIHR Leeds BRC Non Clinical PhD Scheme webinar - YouTube

with a copy of the slide deck used at

 Leeds BRC Non Clinical PhD Webinar FINAL updated slide deck March 24 - YouTube

Biological Sciences (4) Medicine (26)

Funding Notes

The scholarship will provide academic fees at the UK rate, as well as a stipend of £18,622 (based on the 2023/24 stipend rate, pro-rata for part time study) for up to three years (full time study or five years part time) and is available for UK applicants only. Due to limited funding we can only consider applicants eligible to pay academic fees at the UK fee rate.

Where will I study?