Therapeutic applications of adipose-derived stromal vascular fractions in osteoarthritis

Table 1 Clinical trials of stromal vascular fraction in the treatment of osteoarthritis

Main conditions	NCT number	Phase
Osteoarthritis	NCT03818737	Phase III
Osteoarthritis	NCT02846675, NCT02967874	Phase II
Knee osteoarthritis	NCT04050111	Phase II
Knee osteoarthritis	NCT02276833, NCT04043819, NCT03940950	Phase I
		Phase I
Osteoarthritis	NCT03166410, NCT02697682, NCT02726945	Preclinical
		Preclinical
Knee osteoarthritis	NCT04440189, NCT02726945, NCT04440189	Preclinical
		Preclinical

NCT: National Clinical Trial.

Table 2 Clinical researches on the treatment of osteoarthritis with stromal vascular fraction

Ref.	Treatment	Study type	Patients	Follow-up time	Outcome assessments	Consequences
		OA position/number
Pak et al[41,42] (2016, 2018)	SVF + HA + PRP	Case report	3 patients: 1 male, age: 68; 2 females, age: 60 and 87	3.5 mo	FRI, MRI, ROM, VAS	Cartilage repaired showed by MRI; all scores improved
		Knee
Fodor et al[43] (2016)	SVF	Pilot study	6 patients: 1 male, 5 females, mean age: 59	12 mo	ROM, WOMAC, VAS, TUG, MRI	All scores improved, no MRI evidence of cartilage regeneration
NCT02357485		Knee/8 OA
Yokota et al[44] (2017)	SVF	Case report	13 patients: 2 males, 11 females, mean age: 74.5	6 mo	VAS, JKOM, WOMAC	All scores improved
		Knee/26 OA
Nguyen et al[45] (2017)	AM vs AM + SVF + PRP	Comparative study	30 patients (15 per group: 3 males, 12 females) mean age: 58	18 mo	VAS, Lysholm, WOMAC, MRI	All scores improved compared with AM group; AM + SVF + PRP group had obvious cartilage repair show by MRI
NCT02142842		Knee
Michalek et al[46] (2017)	SVF	Case control multi-centric non-randomized study	1128 patients: 596 males, 532 females, median age: 62	17.2 mo	Modified KOOS/HOOS	KOOS/HOOS improved, most patients gradually improved, obesity and more severe OA healed slowly
		Knee and hip/1856 OA
Tantuway et al[47] (2017)	SVF	Case report	101 patients: 41 males, 60 females, age: 29-84	3-24 mo	KOOS	KOOS and joint function improved, pain relieved, patients could move normally
		Knee/201 OA
Russo et al[48,49] (2017, 2018)	SVF	Retrospective study	30 patients: 21 males, 9 females, median age: 43	12-36 mo	Lysholm, VAS, IKDC-subjective, KOOS	41%, 55%, 55%, 64% of the patients improved in the scores, respectively
		Diffuse degenerative keen
Bright et al[50] (2018)	SVF	Case report	1 patient: female, age: 27	3 yr	WOMAC, HOOS	Symptoms of OA reduced, all scores improved, ankylosing spondylitis, depression, anxiety and fatigue improved
		Knee and hip
Barfod et al[51] (2019)	SVF	Prospective cohort study	20 patients, mean age: 49	12 mo	KOOS	KOOS improved
NCT02697682		Knee
Roato et al[52] (2019)	SVF	Case report	20 patients: 9 males, 11 females, mean age: 59.6	18 mo	VAS, WOMAC	Pain relieved, scores improved
		Knee
Hudetz et al[53] (2019)	SVF	Prospective, non-randomized and single center study	20 patients: 15 males, 5 females	12 mo	VAS, WOMAC, KOOS	All scores improved, pain and symptoms relieved for up to a year
		Knee
Berman et al[54] (2019)	SVF	Case report	2586 patients	2-5 yr	Questionnaire (visual acuity pain scores, sustained improvement in function)	Over 80% of patients' pain relieved, joint function improved and maintain 1 yr; outcomes between male and female or between SVF alone and SVF + PRP showed no difference
NCT10953523		Knee
Michalek et al[55] (2019)	SVF	Multicenter case-control study	29 patients: 9 males, 20 females, mean age: 83.3	36 mo	Modified KOOS/HOOS	Apart from 3 elderly patients died from aging, other patients' pain and weekly dosage of analgesics were reduced, KOOS/HOOS improved
		Knee and hip
Yokota et al[56] (2019)	ADSC vs SVF	Retrospective cohort study	ADSC: 42 patients; SVF: 38 patients	6 mo	VAS, KOOS	No major complications occurred, knee joint effusion was more likely to occur in SVF group than ADSC group (SVF 8%, ADSC 2%); VAS and KOOS improved in both groups
		Knee/128 OA
Mayoly et al[57] (2019)	SVF +PRP	Case report	3 patients: 1 male, 2 females, mean age: 62	12 mo	VAS, PRWE, DASH	All scores improved
NCT03164122		Wrist
Hong et al[58] (2019)	SVF vs HA	Double-blind randomized self-controlled trial	16 patients (with bilateral symptomatic knee OA) one side: SVF, the other side: HA. 3 males, 13 females, mean age: 52	12 mo	VAS, WOMAC, ROM, MRI (MOCART, WORMS)	Significant improvement of VAS, WOMAC and ROM in SVF group, but no improvement in HA group; SVF group was superior to HA group in cartilage repair showed by MOCART and WORMS
		Knee
Tran et al[59] (2019)	SVF + AM vs AM	Single-center, non-randomized, placebo-controlled study	33 patients, placebo group (AM): 3 males, 12 females, mean age: 58.2; SVF group (SVF + AM): 5 males, 13 females, mean age: 59	24 mo	VAS, WOMAC, Lysholm, OS	VAS, WOMAC of SVF group reduced significantly compared with placebo group, and maintained 24 mo; Lysholm, OS of SVF group improved
		Knee
Garza et al[60] (2020)	SVF	Double-blinded prospective randomized controlled study	39 patients (randomly assigned to high-, low-dose SVF, or placebo at 1:1:1)	12 mo	WOMAC, MRI	Symptoms and pain relieved by SVF treatment for up to at least 12 mo; changes in WOMAC scores reached statistical significance in the high- and low-dose groups compared to the placebo group; the improvements were dose dependent
NCT02726945		Knee
Lapuente et al[61] (2020)	SVF	Retrospective study	50 patients: 28 males, 22 females, age: 50-89	12 mo	Lequesne, WOMAC, VAS	All scores improved
		Knee/100 OA
Tsubosaka et al[62] (2020)	SVF	Case report	57 patients: 41 males, 16 females, mean age: 69.4	13.7 mo	ROM, WOMAC, VAS, KOOS, MRI	WOMAC, VAS and KOOS improved, while no significant difference in hip-knee-ankle angle, T2 mapping values of lateral femur and tibia improved significantly
		Knee

HA: Hyaluronic acid; FRI: Functional rating index; MRI: Magnetic resonance imaging; VAS: Visual analogue score; ROM: Range of motion; WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index; TUG: Timed up-and-go; JKOM: Japanese knee osteoarthritis measure; AM: Arthroscopic microfracture; OS: Outerbridge classification system; KOOS/HOOS: Knee/hip osteoarthritis outcome score; IKDC: International knee documentation committee-subjective; PRWE: Patient-rated wrist evaluation scores; DASH: Disabilities of the arm and shoulder; MOCART: Magnetic resonance observation of cartilage repair tissue score; BME: Bone marrow edema lesions; WORMS: Whole-organ magnetic resonance imaging score.