Table 4.

Outcome details of the included studies.

Author	Outcome Measures	Follow-Up (Months)	Main Results	Complications	Level of Evidence
Freitag et al., 2020 (Pilot) [56]	WOMAC, KOOS, NPRS, MRI (ICRS score, MOCART score, T2 cartilage mapping)	24	Improvement in pain and function observed, corresponding with MRI imaging analysis showing cartilage regeneration	No serious adverse event occurred	IV
Freitag et al., 2020 [57]	WOMAC, KOOS, NPRS, Patient global impression of change; MRI (MOCART, T2 cartilage mapping)	24	Significant improvements in pain and function were observed, as well as hyaline-like cartilage regeneration	Treatment tolerated with no serious adverse events	IV
Hong et al., 2019 [59]	WOMAC, VAS, ROM, WORMS, MRI (MOCART)	12	VAS, WOMAC and ROM improved in patients with injection of SVF, MOCART revealed improvement of articular improvement compared with hyaluronic acid-treated knees	No severe adverse events observed	II
Jo et al., 2014 [55], 2017 [54]	WOMAC, KOOS, VAS, KSS, Knee pain, MRI (depth of cartilage)	24	Knee function improved (WOMAC, KSS, KOOS), reduced knee pain (VAS), Corresponding with MRI results, showing significant decreased cartilage defect depth at 2 years, as well as significant increased regenerated cartilage volume initially but non-significant from baseline after 2 years. Higher dose cohort has improved clinical outcomes compared with lower doses cohort.	No treatment-related adverse events	III
Kim et al., 2015 [60]	IKDC, Tegner, ICRS	24	Improved IKDC, Tegner activity scores, in both injection and implantation groups. Implantation group has better ICRS outcome compared with injection groups	N/A	III
Koh et al., 2013 [61]	WOMAC, VAS, Lysholm, MRI (cartilage whole-organ MRI score)	24–26	WOMAC, Lysholm, VAS scores improved. Radiography shows improved cartilage whole-organ MRI scores and was related to amount of stem cell injection	N/A	IV
Koh et al., 2014 [62]	IKDC, Tegner, ICRS	24–30	IKDC and Tegner scale scores were significantly improved as well as ICRS overall repair grades	No severe adverse events observed	IV
Koh et al., 2016 [63]	KOOS, symptom subscores, MOCART, ICRS histologic outcomes	24	MRI showed better cartilage coverage of lesion in patients receiving AMSCs with microfracture. Improvement in KOOS scores is significantly greater than in control	N/A	II
Kyriakidis et al., 2020 [64]	KOOS, VAS, IKDC, MRI (MOCART)	36	KOOS, IKDC subjective, Tegner activity, VAS for pain scores were improved. MRI findings showed filling of defect and integration to border zone in 65% of patients. Two patient underwent post-operative biopsies and histological analysis, showing presence of hyaline-tissue	No complications nor treatment-related adverse events were observed	IV
Lapuente et al., 2020 [65]	WOMAC, VAS, Synovial fluid profile, Articular ultrasound; Femoral articular cartilage sonographic evaluation (clarity, integrity, thickness in millimetre)	12	WOMAC, VAS scales improved, correlated with ultrasound observations. Biomarker analysis shows decrease in catabolic and pro-inflammatory pathways and increase in anabolic and anti-inflammatory pathways	No serious adverse event occurred	IV
Lee et al., 2019 [66]	WOMAC, KOOS, VAS, MRI (Modified Noyes grading system, with cartilage defect size)	6	WOMAC Score improvement at 6 months, MRI showed no significant change of defect size in injection group but increased defect in control	No serious adverse event occurred	II
Lu et al., 2019 [58]	WOMAC, VAS, SF-36, MRI (Knee cartilage volume)	12	More patients achieved 50% improvement in WOMAC and more increase in articular cartilage volume of both knees in the injection group than HA group as measured by MRI. Adverse events were comparable	No serious adverse event in injection group, mild moderates Adverse event. Serious Adverse Event of right knee joint infection in the HA group	II
Pers et al., 2016 [67]	WOMAC, KOOS, MRI (dGEMRIC), Histologic analysis, OARSI grading	20	WOMAC improved, dGEMRIC performed on 7 patients, which improved over time for 3 patients but opposite effect in the other 3 patients.	No serious adverse event occurred	IV
Simunec et al., 2020 [68]	KOOS, MRI	12	KOOS scores improved, MRI revealed widening of joint space, restructuring of cartilage and alleviation of effusions in treated joints	No serious adverse event occurred	IV
Spasovski et al., 2018 [69]	VAS, KSS, HSS-KS, Tegner-Lysholm, plain radiography, MRI (MOCART)	18	Improvement of KSS, HSS-KS, T-L scores, and significant improvement in MOCART score; Radiography shows neither improvement nor further joint degeneration	No serious adverse event occurred	IV
Song et al., 2018 [70]	WOMAC, NRS-11, SF-36, MRI (cartilage volume)	22 (96 weeks)	AMSCs improved pain, function and cartilage volume in the knee joint, with a dose-dependent effect	No serious adverse event occurred	IV
Zhao et al., 2019 [71]	WORMS, MRI	11 (48 weeks)	Improvement in WOMAC and SF-36 scores; Changes in T1rho, T2, T2star, R2star and ADC measurements suggests possible compositional changes in cartilage	No serious adverse event occurred	II
Zhou et al., 2021 [72]	WOMAC, VAS, MRI (MOCART)	12	WOMAC, VAS rest, VAS motion scores were found significantly lower than control group; MOCART scores of experiment groups were found significantly higher than experiment group; No significant difference in WOMAC stiffness scores	No serious adverse event occurred	II

Abbreviations: WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index; VAS, Visual Analogue Scale; KOOS, Knee injury and Osteoarthritis Outcome Score; KSS, Knee Society Score; HSS-KS, Hospital for Special Surgery Knee Score; ROM, Range of Motion; NRS-11, Numeric Rating Scale-11; NPRS, Numeric Pain Rating Scale; SF-36, Short Form Health Survey-36; MRI, Magnetic Resonance Imaging; MOCART, Magnetic Resonance Observation of Cartilage Repair Tissue; WORMS, Whole-organ MRI score; dGEMRIC, delayed gadolinium-enhanced MRI of cartilage; ADC, Apparent diffusion coefficient; ICRS, International Cartilage Repair Society; IKDC, International Knee Documentation Committee.