Workshop 1

Using MSCs to produce chondrocytes with stable phenotype (how to successfully direct stem cell differentiation)

Improved characterisation of the type of cells used in ACI (i.e. phenotype of chondrocytes, ?presence of SC in the cell population which may be contributing to the repair process, exclusion of synoviocytes)

Role of quality of tissue surrounding the defect site (lateral integration, quality of repair tissue produced)

Role of the area of the knee joint from which the biopsy is taken (weight-bearing vs non-weight bearing)

Instruments used for assessment of functional outcome

Focus on cell type to be used (i.e. chondrocyte vs stem cell or growth factors; importance of stem cell niche to direct differentiation)

Effect of surrounding environment on ACI success (cartilage surrounding defect site/synovial fluid)

Problem with ACI is that it is an expensive procedure with significant cost for rehabilitation Will the ACTIVE trial evaluate which rehabilitation protocol is best?

Surgeon education

Identification of appropriate clinical indications for microfracture/ACI both at the clinical and tissue/molecular level

Development of chondrocyte bank (what type of chondrocytes to be used foetal#mature)

Development of one-step procedure

What is the optimal number of cells to be transplanted

Does synchronous osteotomy affect micro-environment in terms of healing/differentiation/quality of tissue produced?

Genetic modification of MSC to control differentiation/Selecting MSC derived from cartilage in order to optimise chances of successful differentiation

Workshop 2

Appropriate clinical indications and patient selection to optimise chances of success:

  • Microfracture for lesion <2.0cm2
  • Location of defect and selection of appropriate treatment
  • Synchronous procedures (ACL/Osteotomy)

Determination of whether ACI is more appropriate (best chance of success) as a primary treatment vs. 2nd/3rd procedure

What is the best clinical measure of success?

  • Histology
  • Functional Scores
  • MRI/Radiology

What is the ideal functional scoring system for articular cartilage defects?

Consider RCTrial of ACI as primary treatment vs other primary treatment

Consider RCTrial of ACI as standard but looking into different rehabilitationprotocols

How long does it take for implanted cells (ACI/MACI) to attach to the subchondral plate?

  • 72hrs
  • 1 – 2 Weeks

And the relevance of the timing to post-op rehabilitation protocol (i.e. casting vs. CPM)

Importance for the development of a central database

Workshop 3 – Problems of Assessing Results

What groups of patients do surgeons see?

S C O R I N G
V A R I A B L E S /
  • symptomatic/severity of symptoms/lifestyle impact
  • previous surgery
  • variable symptoms & requirements
  • underlying pathology (isolated defect vs. early OA vs. advanced OA)
  • lifestyle choices
  • adequate history – age, activity, occupation
  • motivation factors/expectations

Randomization choices for standard 3-4cm2 lesions

  1. RNOH – AMIC vs. MACI/ACI-C
  2. Cheshire – AMIC vs. MACI/Chondron
  3. Andrew Price – Microfracturevs.ACI
  4. James Richardson – AMIC vs. ACI c/p
  5. Mintowt-Czyz – AMIC vs. ACIp

How to best measure outcome? /Which is the best functional outcome score?

Lysholm – excluding question on swelling

QOL – SF36 / EQ5D

IKDC2000

Postal score

KOOS

VAS

PFOS

Important characteristics:

  • Simple for patient to use
  • Advice from bio-statistician
  • What is the primary outcome that you aim to measure with your score?
  • Time to failure of the given treatment as an outcome measure?
  • Change from baseline
  • Repeated assessments
  • Assessment at 2 years post treatment as predictor of final outcome

Workshop 4 – Future planning of clinical trials

Patient groups

  • Primary treatment
  • Failed primary treatment
  • End stage OA in patients 50yrs

Multicentre RCT

  • Primary treatment – micro# vs debridement vs physio
  • Failed primary treatment – ACI vs. AMIC
  • End stage OA patients – ACI+HTO vs. UKA

Strategy for acquiring funding

  • ICRS UK coordinating role
  • Clinical networks
  • Surgeon input
  • Teamwork – group resource
  • Application so HTA/Funding bodies
  • Maximum of 2 centrally funded RCTs in cartilage repair at any time

Discussion

  • Set up a register to collect pilot data prior to design of next RCT
  • Build a network
  • Complete ACTIVE
  • Arthroscopic Cell Therapy vs ACI
  • Different Rehabilitation regimes