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

Table 2 Clinical and in vivo/in vitro experimental data

Experiment type	Cell source	Main observed data	Comparative effects	Ref.
In vitro experiment	BMSCs, NPC	NP cell survival rate, ECM production	BMSCs and NPCs in coculture significantly increased NP cell survival and promoted the generation of type II collagen and proteoglycans. In a hypoxic environment, TGF-β and Notch pathways enhanced disc microenvironment repair	[16,67]
In vivo experiment	BMSCs, UC-MSCs	Disc height, NP cell count, NP cell apoptosis rate	Intradiscal injection of BMSCs and UC-MSCs significantly reduced NP cell apoptosis and restored disc height. Exosomes combined with hydrogels improved stem cell engraftment in the disc	[32,55]
Clinical trial	BMSCs	Pain relief, functional recovery, disc water content	Early clinical trials of BMSC injections showed significant pain reduction in patients, with increased NP water content at 12-month follow-up, confirming BMSC repair potential. Several studies showed significant pain relief postinjection with no severe side effects	[20]
In vitro test	ADSCs	Pain score, functional improvement, disc regeneration	ADSC injections demonstrated significant pain relief and functional improvement in patients with lower back pain, with substantial reductions in pain scores and no reported severe complications	[25]
Animal experiment	BMSC exosomes	ECM production, disc height, inflammation	BMSC exosomes significantly enhanced NP cell antiapoptotic capacity, promoted ECM synthesis, and restored disc structure and elasticity. Exosomes reduced inflammation in disc degeneration models by activating the PI3K/AKT pathway	[11]
In vitro test	BMSC and ADSC exosomes	Disc repair rate, inflammation modulation, cell survival	Stem cell-derived exosomes promoted disc repair by reducing inflammation and enhancing NP cell survival, showing significant therapeutic potential when combined with gene editing technology and biomaterials	[90,91]

BMSCs: Bone marrow-derived mesenchymal stem cells; ADSCs: Adipose-derived mesenchymal stem cells; UC-MSCs: Umbilical cord-derived mesenchymal stem cells; NP: Nucleus pulposus; ECM: Extracellular matrix; TGF: Transforming growth factor; PI3K: Phosphatidylinositol 3-kinase; AKT: Protein kinase B; NPC: Nucleus pulposus cells.