Table 2.

Clinical trials using MSCs in OA.

Year	References	Sample	Source of MSC	Injection method	Treatment group	Result
2015	Kim et al. (115)	49 patients	AT-MSCs	Loaded into fibrin glue product to be surgically implanted into lesion site	Patients received approximately same amount of MSC (4.3 × 106) via arthroscopic procedure	Patients showed overall satisfaction with improved mean IKDC and Tegner activity scores. Regarding the efficacy of MSC implantation, it was concluded that there was a cutoff for both age (>60 years old) and cartilage lesion size (>6.0 cm2)
2016	Shapiro et al. (116)	25 patients	BM-MSCs	Combined with platelet-poor plasma for injection	25 patients were randomly divided into two groups. 12 patients had BMAC injected in their left knee and placebo in their right, while 13 patients were injected BMAC on their right knee and placebo in their left. The BMAC product had a median of 34,400 MSCs	Significant improvements in ICOAP scores, VAS pain scores, activity level, and pain medication usage were observed from both placebo and treated knees. No adverse events were reported which ensured the safety of MSC treatment
2016	Pers et al. (117)	18 patients	AT-MSCs	Intra-articular injection in the knee joint	18 patients were divided into 3 cohorts with increasing dosage: 2 × 106 (low dose), 10 × 106 (medium dose), and 50 × 106 (high dose)	Only the low dosage group showed statistically significant improvements in all categories of WOMAC index, VAS pain score, and KOOS index. The medium dose group showed improvements in some categories. The high dose group did not have any statistically significant results. Thus, there was an inverse dose effect
2018	Matas et al. (118)	26 patients (with 8 serving as controls)	UCB-MSCs	Intra-articular injection	Patients in the control group received hyaluronic acid treatment and MSC-treated patients were divided into two groups (n = 9). The first group received single dose of UCB-MSC (20 × 106), while the second group received two dosages (20 × 106) 6 months apart	Some patients in MSC treated groups showed acute synovitis after injection. No serious adverse events were reported. Improvements in pain and function with lower WOMAC and VAS pain scores was observed compared to the control group without any differences in MRI scores
2019	Freitag et al. (119)	30 patients (with 10 serving as controls)	AT-MSCs	Intra-articular injection	Patients were separated equally into three groups (n = 10). The control group continued to receive conventional conservative management. The first treatment group received one MSC injection (1 × 108 AT-MSCs). The second treatment groups received two injections 6 months apart (1 × 108 AT-MSCs)	The two treated groups saw significant reduction in pain measured by NPRS and WOMAC scores. MSC injection was also concluded to reduce the rate of cartilage loss upon MRI analysis. Although minor discomfort and bruising was common for treated groups, no serious adverse events were reported
2019	Chahal et al. (120)	12 patients	BM-MSCs	Intra-articular injection	Patients were divided into four cohorts (n = 3). Each group received a single intra-articular injection of BM-MSCs. The first three cohorts received (1 × 106, 10 × 106, and 50 × 106 of BM-MSCs) The fourth cohort had each patient receive the different dosages of MSC listed above	Although four patients reported pain and swelling after injection, no other serious adverse events were reported. Patients who received higher dosages of MSCs saw more significant improvements in KOOS, WOMAC stiffness, quality of life, and symptoms
2019	Lee et al. (121)	24 patients (with 12 serving as control)	AT-MSCs	Intra-articular injection	Patients in the treated group received inter-articular injection of AT-MSC (1 × 108) in 3 mL of saline	The MSC treated group showed significant improvements in WOMAC and VAS scores. Furthermore, the size of the cartilage defect was increased in the control group, while no significant change was observed in the MSC group. No serious adverse events were reported