Project title: Identification and validation of tissue-resident human Skeletal Stem Cells (hSSC) in the 1^st Carpo-metacarpal Joint (CMCJ) of osteoarthritic (OA) patients.

Grant Holder: MATTHEW P MURPHY

Position: Academic Clinical Fellow in Plastic Surgery,

North West (East) Deanery, University of Manchester, United Kingdom.

Date of award

15/11/2021

Start date for research

04/01/2022

Date of report

19/01/2023

Grant Awarded (i.e. £10,000)

£10,000

Is this an interim, or final, report

Interim

Summary of project/progress /findings (approx 300 words)

COMPLETED
As part of the original team at Stanford who discovered the human skeletal stem cell (SSC), I have been fortunate to return to Stanford to continue my research during my ACF 6 month research block. During this time I have been involved in establishing a research project to identify the presence of tissue-resident SCC in the trapezium of human subjects who suffer from 1st CMCJ OA.
By using Fluorescence-Activated Cell Sorting (FACS), I have successfully isolated human SSC from osteoarthritic trapezium. The tissue components where, by FACS, SSC appear to exist are the bone, cartilage and soft tissues (periosteum, ligament, tendon insertion). The SSC isolated from each tissue component have shown the ability to differentiate into bone, cartilage in vitro with an inability to differentiate into fat (FIGURE 1). These data suggest that these SSC behave in a similar fashion to the SSC isolated from other specimens previously investigated (femoral heads, foetal long bones, fracture samples etc).
While at Stanford I established a large animal porcine study investigating the key growth factors applied locally to cartilage defects that allow for robust regeneration of cartilage. Through Growth factor Enhanced Micro-fracturing (G.E.M) I have been able to regenerate cartilage in a large animal model defect model (FIGURE 2).

ONGOING
While I have shown their ability to differentiate in vitro I am continuing to confirm their ability to differentiate in vivo to determine their cell-intrinsic characteristics. To do this I am isolating SSC from trapezium samples and will be injecting them into the renal capsule
of NSG RFP mice. Following 6 weeks I will then harvest the tissues to determine what tissue the SSC have differentiated into on histological examination. Data collection is ongoing.

What is the relevance/value of this research to hand surgery:

By determining that osteoarthritic trapezium specimens do have a population of tissue-resident SSC, theoretically one should be able to activate the tissue-resident SSC population and encourage regeneration of cartilage through niche augmentation. The ability to regenerate cartilage will provide an additional tool in the hand surgeons armamentarium in treating 1st CMCJ OA.

If final report, please provide bullet point list of conclusions/important findings

• N/A

Please list presentations based on work performed in this study

            IAPS 2022, TERMIS March 2023, RCSEng HUNTERIAN LECTURE 2023.

Please list publications based on work performed in this study

             Manuscript in progress.

Please state what additional research this study has/is leading to

• A large animal study preclinical translational study at Stanford.
• Describe pre-clinical work in Manchester

Please list any further funding or grant applications (with outcome), which have resulted from the award of this grant

• N/A

How has this grant awards helped your career development?

• Being awarded this grant has enabled me to continue my collaboration with Stanford University which has been instrumental in bridging my career progression from ACF to further independence.