Table 4.

Conditioned mediums, exosomes, and co-cultures for inducing mesenchymal stem cell differentiation into intervertebral disc cells.

Factors	Effects and Examples of Usage	References
CM (NCCM, 1 × 106 cells/5 mL [168]; NPC-CM, not specified, P3 [169])	NCCM exhibited a stronger effect on the chondrogenic differentiation of BMSCs compared to CDM in combination with hypoxia, which is necessary for NPC-CM to induce the chondrogenic differentiation of BMSCs	[168,169]
Exosomes (1 × 106 cells/5 mL [170])	NPC exosomes promote the differentiation of BMSCs into an NPC-like phenotype mediated by the Notch 1 pathway	[170,171]
Co-culture (1 × 106 cells/mL, 1:1 [56]; 2 × 106 cells/mL, 1:1 [57]; 1 × 105 cells/0.5 cm3, 1:1 [75]	The co-culture of MSCs with NPCs or AFCs differentiates MSCs into NPC or AFC-like cells; the co-culture of MSCs with IVD tissue differentiates MSCs into NPC-like cells in combination with dynamic compression or bilaminar cell pellets, which have synergistic effects	[56,57,68,72,75,76,177,178,179,180,181,182,183,184,185,186,187]

AFC, annulus fibrosus cell; BMSC, bone marrow-derived MSCs; CDM, chondrogenic differentiation medium; CM, conditioned medium; IVD, intervertebral disc; MSCs, mesenchymal stem cells; NCCM, conditioned medium of notochordal cells; NPC, nucleus pulposus cell; NPC-CM, NPC-conditioned medium.