Stem Cells for Cartilage Repair: Preclinical Studies and Insights in Translational Animal Models and Outcome Measures
Table 1
Key factors for the selection of a translational animal model for cartilage repair.
Aspect
Remark/recommendation
Anatomy and biomechanics
(i) Large difference in anatomy and biomechanics remains between animal models and humans
Cartilage thickness
(i) Large animals provide closer proximity to the human condition
(ii) Depends on topographic location in joint
Subchondral bone properties
(i) Effect on repair mechanisms
(ii) Depends on topographic location in joint
Defect dimensions and location
(i) Critical size chondral or osteochondral
(ii) Location of defect influences cartilage repair
(iii) Femoral condyles or trochlea
(iv) Defect should be made based on the biomechanics of the joint of the animal
Age and gender
(i) Age and gender may have effect on repair mechanism
(ii) Inclusion of skeletally mature animals with mature cartilage (human—near puberty)
(a) Rabbit—8 months
(b) Dog—24 months
(c) Pig—18 months
(d) Sheep—24 months
(e) Goat—24 months
(f) Horse—24 months
(iii) Gender effects must be taken into consideration
(iv) Use animals with short range of ages and with similar sex
Study duration
(i) Depends on type of study
(ii) Proof-of-principle (<6 months) versus late-stage study (6 months–12 months)
Surgical and practical considerations
(i) Unilateral versus bilateral repair models
(a) Unilateral models: evaluation of locomotion, range of motion and gait, better immobilization, and no influence of contralateral technique
(b) Bilateral models: minimize interanimal variability
(ii) Postoperative management should be tolerated
(iii) Ethical permission for small animals and ruminants is easier to obtain
(iv) Surgical feasibility must be taken into account
(v) Financial costs to house and handle differ variously between animals
(vi) Availability of facilities, competent personnel, and equipment
Validated outcome measures
(i) At baseline, in vivo and post mortem
(ii) Clinical response and kinematics
(iii) Biological fluid collection
(iv) Noninvasive compositional imaging MRI
(v) Ex vivo high resolution magnetic resonance imaging (MRI) or microcomputed tomography (μCT)
(vi) Tracking and monitoring
(vii) Macroscopic/arthroscopic scoring
(viii) Histological and histomorphometric scoring
(ix) Mechanical testing
(x) Biomolecular and biochemical testing