Table 2 Recent preclinical studies on ADSC-based optimization strategies for cartilage regeneration
ADSC-based optimization strategies | Models | Methods | Results | References | |
|---|---|---|---|---|---|
ADSCs | Â | 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 | Â | 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] |
| Â | 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] |
| Â | 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] |
| Â | 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] |
| Â | 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] |
| Â | 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] |
| Â | 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] |