Stimulatory cells Chondrogenic cell Culture system Cell ratio direct/ indirect Co-culture effect Reference Articular chondrocytes with heterotopic chondrocytes AC (porcine) AU & NS (porcine) poly glycolic acid (PGA) 1:1 direct ↑coll. typ II/I ratio [31] AC (porcine) AU alginate ML 1:1 direct not significant [30] AC (bovine) variable passage AC (bovine) agarose ML variable direct indirect ↑coll. type II, PG, biomechanics [33] AC (juvenile) AC (adult) agarose 1:1, 1:3, 1:8 direct ↓PG [24] ddAC (rat) passage 0-4 healthy or oa AC (rat) agarose/monolayer --- indirect ↑proliferation [74] AC (bovine) passage 0 dd AC (bovine) passage 2 on filter inserts 5-40% dd AC direct redifferentiation ↑coll. type II/I ratio [27] AC of the deep zone (bovine) AC (superficial or middle zone) (bovine) monolayer 1:1 direct ↓ALP/mineralisation [45] AC of the superficial zone (bovine) AC of the middle zone (bovine) monolayer 1:3, 1:1, 3:1 direct ↑lubricin ↓PG [44] AC of the superficial zone (bovine) AC of the middle zone (bovine) poly(ethylene) oxide bilayer hydrogel 1:1 direct ↑PG, coll. content, biomechanics ↓proliferation [43] AC (bovine) passage 0 dedifferentiated AC (bovine) passage 2 mass culture/monolayer 1:4 direct redifferentiation ↑coll. type II/I ratio [28]

Stimulatory cells Chondrogenic cell Culture system Cell ratio direct/ indirect Co-culture effect Reference  Articular chondrocytes and osteoblast OB (rat) AC (bovine) ML insert 1:2 direct indirect ↑coll. II, aggrecan, proliferation, ALP [67] sclerotic OB (human) oaAC (human) alginate insert --- indirect ↓coll. II, SOX9 and PTHrP/-R suppressed in AC [9] Articular chondrocytes and fibroblast AC (porcine) DF (human) PLGA 1:1 direct lacunae formation by DF [65] Articular chondrocytes with embryonic stem cells AC (human) ESC (human) pellet hyaluronan based scaffold agarose 1:1 direct ESC gain abilities to grow on plastic, to form colonies in agarose, and to produce cartilage specific ECM [52] AC & FC (bovine) ESC (human) ESC pellet / insert --- indirect ↑coll. II, GAG, proliferation [53] AC (human) ESC (human) insert --- indirect ↑coll. II, coll. I, collagen content, GAG, SOX9 [54] AC: Articular Chondrocytes; ALP: Alkaline Phosphatase; AU: Auricular; COMP: Cartilage Oligomeric Protein; coll.: Collagen; CRTL1: Cartilage Link Protein1; ITGA1: β1- integrin; dd: dedifferentiated; DF: Dermal Fibroblasts; ESC: Embryonal Stem Cells; FC: Fibro-chondrocytes; IHH: Indian Hedgehog; MIA: Melanoma Inhibitory Activity; ML: Monolayer; MSC: Mesenchymal Stem Cells; NS: Nasoseptal; oa: osteoarthritic chondrocytes; OB: Osteoblasts; PEODA: Poly(ethylene oxide) diacrylate; PG: Proteoglycans; SOX9: SRY (Sex Determining region Y)-box 9.

Table 1a: Co-culture studies combining articular chondrocytes with other chondrogenic cells.

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