Stem cell therapy for intervertebral disc degeneration: Clinical progress with exosomes and gene vectors

Table 5 Applications of combining gene editing with biomaterials in stem cell therapy

Technology/material type	Target gene/material	Main mechanism of action	Application scenario	Experimental results	Ref.
CRISPR-Cas9	Parkin	CRISPR-dCas9-KRAB system used to silence the expression of Parkin	Targeting Parkin provides a new approach for IVDD repair	Inhibition of Parkin significantly reduces mitophagy and accelerates apoptosis of NPCs	[128]
siRNA	Bcl-2	Reduces apoptosis by inhibiting the expression of apoptosis-related gene Bcl-2	Inhibition of NPC apoptosis	Decreases the apoptosis rate of NPCs, promoting disc tissue repair	[113,114]
Gene editing + hydrogel	HIF-1α	Enhances HIF-1α expression in hypoxic environments, improving stem cell survival	Disc regeneration and cell protection under hypoxic conditions	Significantly improves stem cell colonization and survival, promoting regeneration of nucleus pulposus tissue	[26,27]
Gene editing + chitosan	IGF-1	Enhances IGF-1 expression, promoting cell proliferation and differentiation	NP tissue repair and regeneration	Increases the proliferation rate of NPCs, enhances type II collagen and proteoglycan production	[123]
Nanofiber scaffold	No gene editing	Provides 3D structural support, enhancing stem cell colonization efficiency	Tissue regeneration and structural repair	Nanofiber scaffold provides ideal mechanical support, significantly improving tissue structure restoration	[112]
CRISPR + exosome	miRNA	Increases miRNA content in exosomes, regulates inflammation, and promotes tissue repair	Inflammation control and disc regeneration	Significantly reduces inflammation, promotes ECM production, and enhances cell repair capacity	[30]
Gene editing + nanoparticles	VEGF	Overexpression of the VEGF gene increases angiogenesis, improving blood supply to the disc	Disc vascularization and regeneration	Promotes angiogenesis in disc tissue, enhancing regeneration capacity	[30,128]

siRNA: Small interfering RNA; HIF: Hypoxia-inducible factor; IGF-1: Insulin-like growth factor 1; miRNA: MicroRNA; VEGF: Vascular endothelial growth factor; ECM: Extracellular matrix; NPC: Nucleus pulposus cells; NP: Nucleus pulposus; 3D: Three-dimensional; IVDD: Intervertebral disc degeneration.