Clinical trial NCT06167928: Developing Allogeneic Musculoskeletal Therapies
Official title: Investigating the Potential for Musculoskeletal Tissues and Cells Isolated From Juvenile Patients in the Development of Novel Therapies for Cartilage and Bone Injury and Osteoarthritis
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Osteoarthritis
Keywords: Cell therapy
Musculoskeletal
Allogeneic
Lead sponsor: Keele University
Sponsor class: OTHER
Collaborators: name: Alder Hey Children's NHS Foundation Trust
name: Birmingham Women's and Children's NHS Foundation Trust
name: Norfolk and Norwich University Hospitals NHS Foundation Trust
name: Royal National Orthopaedic Hospital NHS Trust
name: Scottish National Blood Transfusion Service
name: NHS Blood and Transplant
name: University of Birmingham
name: Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
name: The Royal Orthopaedic Hospital NHS Trust
First posted: 2023-12-13
Enrollment: 325
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Juvenile/infant donors:

Participants between 0-4 years of age scheduled for polydactyly digit amputation or hip dislocation surgeries at the RJAH Orthopaedic, Alder Hey, Norwich and Norfolk, Royal National Orthopaedic and Birmingham Women's and Children's Hospitals (where appropriate i.e. polydactyly only at Alder Hey, and Norwich and Norfolk.

Biobank/NHSBT donors:

Participants of any age that have consented to donating their cartilage tissues to a bio-bank.

Brief summary: The goal of this observational study is to analyse the cartilage and bone forming potential of cells isolated from the tissues of patients undergoing surgery for the treatment of polydactyly, hip dislocation and from other bio-banked cartilage tissues. The main question it aims to answer is:

Which of the following tissues from polydactyly digit, iliac apophysis or other bio-banked cartilage produce better cartilage in vitro and in vivo? Participants receiving digit amputation surgery for treatment of polydactyly will be asked to donate the associated waste tissue whilst participants receiving surgery to treat a dislocated hip will be asked to donate an extra small piece of cartilage tissue (approximately 1 gram) from the iliac apophysis. Other tissues for the study will be obtained from those donated to biobanks.

Detailed description: Cartilage and bone injury and osteoarthritis (OA) continues to take its toll on the quality of life of a large proportion of the world's population. Clinicians and scientists at the Robert Jones \& Agnes Hunt Orthopaedic Hospital (RJAH) are part of the Versus Arthritis Tissue Engineering Centre. The investigators have a long history of developing innovative cell-based therapies for the treatment of cartilage and bone defects and osteoarthritis, such as, autologous chondrocyte implantation, which is considered a successful treatment for chondral defects.

However, there are potential drawbacks to the use of this procedure to treat larger osteochondral defects that arise in OA. These include the potential shortage of cartilage tissue available in OA patients and the fact that those cells obtained may have phenotypes preventing the reproduction of good quality cartilage. It is therefore favourable to seek a source of cells optimal for osteochondrogenesis for every patient.

To further our studies the investigators wish to collect amputated digits that are removed in the routine treatment of polydactyly. The investigators also intend to study cells isolated from the iliac apophysis, these tissues will be removed during surgeries in the treatment of dislocated hips. In addition, the investigators intend to receive joint tissues from collaborative orthopaedic hospital tissue biobanks and National Health Service Blood and Transplant (NHS-BT). Our intention is to study the potential of cells derived from these tissues in the treatment of other patients with cartilage or bone injuries or osteoarthritis.

In the first instance, the investigators propose to evaluate the use of various sources of cells for musculoskeletal therapies including bone, bone marrow and cartilage, although skin, fat and other tissues might also be attractive sources. Stem cells derived from these tissues are known to be capable of differentiating into cells which might be suitable for musculoskeletal repair strategies, i.e. osteoblasts and chondrocytes, to form bone and cartilaginous tissues. Thus these cells are attractive candidates for allogenic cell therapies for treatment of OA tissue damage. Furthermore the expected high vitality of the juvenile cells may allow for several patients to be treated by one characterised source. This will help to lower the cost of providing a cell therapy.

Eligibility criteria: Inclusion Criteria:

For juvenile/infant donors:

* Parents/guardians being able to provide signed and dated informed consent form.
* Scheduled for one of the following surgical treatments:

Digit amputations due to polydactyly. Surgery to treat dislocated hips.

For biobank/NHSBT donors

* Informed consent via consenting institution.

Exclusion Criteria:

* Parents/guardians not understanding the Patient Information Sheet

Primary outcomes:
measure: Cell viability as assessed by trypan blue exclusion assay
timeFrame: Up to 48 hours
Secondary outcomes:
measure: Measure levels of glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay
timeFrame: Up to 3 months
Other outcomes:
Locations:
city: Oswestry
country: United Kingdom
facility: Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
state: Shropshrie
Study officials:
affiliation: ISTM, Keele University
name: Karina T Wright, PhD
role: PRINCIPAL_INVESTIGATOR
References: