Table 6.

Environmental factors for inducing mesenchymal stem cell differentiation into intervertebral disc cells.

Factors	Effects and Examples of Usage	References
Hypoxia	Promotes MSC differentiation toward an NPC-like phenotype; confers agonistic effects to NPC-CM treatment on BMSC differentiation toward NPC-like cells; highly relevant to HIF-1α activity	[77,78,79,169,242,243,244]
Hyperosmolarity	Whether high osmotic pressure promotes the differentiation of MSCs into NPC-like cells remains controversial	[251,252,253,254]
Mechanical stresses	A low cyclic and dynamic compressive load and a simulated-physiological compressive load promote the differentiation of MSCs into NPC-like cells	[7,70,224,256,257,258,259,260,261,262,263,264]

BMSC, bone marrow-derived MSCs; CM, conditioned medium; HIF-1α, hypoxia-inducible factor-1α; MSC, mesenchymal stem cell; NPC, nucleus pulposus cell.