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