Table 2.

Recent preclinical studies on ADSC-based optimization strategies for cartilage regeneration

ADSC-based optimization strategies		Models	Methods	Results	References
ADSCs		Rat osteoarthritis model	ADSCs were injected into the articular cavity	ADSCs inhibited the expression of NLRP3, Caspase1, GSDMD, and TNFR1; improved the pathological changes in the joints; and delayed osteoarthritis development	Xu et al. [107]
ADSC-EVs		Rat osteoarthritis model	ADSC-EVs were injected into the articular cavity	ADSC-EVs protected the cartilage from degeneration, inhibited the infiltration of M1 macrophages into the synovium, and attenuated osteoarthritis progression	Woo et al. [21]
ADSC-Exos	Hypoxic pre-condition of ADSCs	Rat model of post-traumatic osteoarthritis	Intra-articular injection of hypoxia-cultured ADSC-secreted exosomes (hypoxia-ADSC-Exos)	Hypoxia-ADSC-Exos exhibited a chondroprotective effect and suppressed osteoarthritis progression	Chang et al. [114]
	Tropoelastin pretreatment of ADSCs	Rat model of osteoarthritis induced by the anterior cruciate ligament transection (ACLT)	Intra-articular injection of exosomes from tropoelastin-pretreated ADSCs (TE-ADSCs-Exos)	TE-ADSCs-Exos enhanced matrix synthesis and promoted cartilage repair	Meng et al. [115]
Bioscaffolds	Biomimetic injectable hydrogel using amnion membrane (AM)	Collagenase-induced osteoarthritis rat model	Intra-articular injections of AM hydrogels with ADSCs	AM hydrogels with or without ADSCs alleviated inflammation and cartilage degeneration	Bhattacharjee et al. [18]
	Glycol chitosan/dibenzaldehyde- functionalized- polyethylene glycol (GCS/DF-PEG) hydrogel	Rat model of articular cartilage defect	ADSCs with GCS/DF-PEG hydrogel were injected into the defective area	ADSCs and GCS/DF-PEG hydrogel complexes exhibited obvious cartilage regeneration ability	Yang et al. [119]
	Coacervate-embedded gelatin-SH/PEGDA IPN hydrogels	Rabbit femoral trochlear osteochondral defect model	ADSCs and IGF-1 were transplanted with coacervate-embedded composite hydrogels	Dual delivery platform could induce chondrogenic differentiation of embedded ADSCs and promote osteochondral tissue regeneration	Cho et al. [123]
	Acellular cartilage extracellular matrix (ACECM) scaffolds	Pig osteochondral defect model	ADSCs combined with ACECM were transplanted into the defective area	ADSCs-ACECM composites successfully repaired the cartilage defect	Lu et al. [120]
Genetic modification	Chemically modified mRNA (modRNA)-mediated IGF-1 gene transfer	Mice osteoarthritis model	IGF-1-ADSCs were injected into the articular cavity	IGF-1-ADSCs decreased the loss of cartilage ECM, promoted cartilage repair, and exerted a chondroprotective effect	Wu et al. [68]
	ADSCs were transfected with miR-486-5p	Rat osteoarthritis model	Intra-articular injection of miR-486-5p-modified ADSC-Exos	miR-486-5p-modified ADSC-Exos attenuated chondrocyte apoptosis and alleviated osteoarthritis	Wang et al. [125]
Genetic modification + Bioscaffolds	Genetically engineered ADSCs overexpressing TGF-β1 (T-ADSCs); An injectable extracellular matrix (ECM)-mimicking hydrogel	Rat osteoarthritis model	T-ADSCs and hydrogels were injected into the articular cavity	T-ADSC-loaded hydrogels markedly reduced cartilage degeneration, joint inflammation, and subchondral bone loss	Yu et al. [67]
	ADSCs transfected with miR-99 b-3p-mimic; Hyaluronan-based hydrogel microparticles (HMPs)	Mice osteoarthritis model induced by surgical destabilization of the medial meniscus (DMM)	miR-99 b-3p-overexpressing ADSC-Exos were encapsulated in HMPs and injected into the articular cavity	miR-99 b-3p-modified ADSC-Exos combined with HMPs inhibited the degradation of the cartilage ECM	Yin et al. [126]