Developing Allogeneic Musculoskeletal Therapies

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

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.

Study Overview

• Status: Recruiting
• Conditions: Osteoarthritis

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.

• Study Type: Observational
• Enrollment (Estimated): 325

Contacts and Locations

• Study Contact: Name: Karina T Wright, PhD; Phone Number: +441691404022; Email: karina.wright1@nhs.net
• Study Contact Backup: Name: Sharon J Owen, PhD; Phone Number: +441691404295; Email: sharon.owen12@nhs.net

Study Locations

• United Kingdom
  • Shropshrie
    • Oswestry, Shropshrie, United Kingdom, SY10 7AG
      • Recruiting
      • Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust
      • Contact: Karina T Wright, PhD; Phone Number: +441691404022; Email: karina.wright1@nhs.net
      • Principal Investigator: Karina T Wright

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cell viability as assessed by trypan blue exclusion assay	The viability of cells post-collagenase digest will be assessed by trypan blue exclusion assay	Up to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure levels of glycosaminoglycan content by 1,9-dimethylmethylene blue (DMMB) assay	Glycosaminoglycan levels will be measured post-chondrogenic induction by DMMB assay	Up to 3 months

Collaborators and Investigators

• Sponsor: Keele University
• Collaborators: Norfolk and Norwich University Hospitals NHS Foundation Trust; University of Birmingham; Royal National Orthopaedic Hospital NHS Trust; Alder Hey Children's NHS Foundation Trust; Birmingham Women's and Children's NHS Foundation Trust; NHS Blood and Transplant; Robert Jones and Agnes Hunt Orthopaedic and District NHS Trust; The Royal Orthopaedic Hospital NHS Trust; Scottish National Blood Transfusion Service
• Investigators: Principal Investigator: Karina T Wright, PhD, ISTM, Keele University

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2018
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): September 1, 2037

Study Registration Dates

• First Submitted: November 21, 2023
• First Submitted That Met QC Criteria: December 12, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Actual): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Allogeneic; Cell therapy; Musculoskeletal
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis
• Other Study ID Numbers: RG-0245-17-ISTM; 21157 (Other Grant/Funding Number: Versus Arthritis); MR/5015167/1 (Other Grant/Funding Number: MRC); 225835 (Other Identifier: Health Research Authority (HRA) UK); 17/NW/0550 (Other Identifier: REC - North West - Liverpool East)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No