Adipose-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage: A Systematic Review on Preclinical and Clinical Evidence

Table 2

(a) Clinical studies performed on animals. (b) Clinical studies performed on humans.

(a)

Ref.	Study type	Animal	Pathology	Cell type and source	Injection/implantation	Study design	Follow-up	Results
Black et al. 2007, Vet Ther [47]	Randomized blinded placebo-controlled	Dogs	OA	Concentrated ADSCs, from abdominal area, inguinal, or thoracic wall regions	1 injection	(i) ADSCs; (ii) placebo	90 days	Significantly improved scores for lameness and the compiled scores for lameness, pain, and range of motion compared with control dogs
Black et al. 2008, Vet Ther [46]	Case series	Dogs	OA	Concentrated ADSCs, from abdominal area, inguinal, or thoracic wall regions	1 injection	(i) ADSCs	180 days	40% improvement in lameness, range of motion, and pain on manipulation over time compared with baseline values
Guercio et al. 2012, Cell biology international [48]	Comparative	Dogs	OA	Expanded, from abdominal area, subcutaneous, visceral, and inguinal fat depots	1 injection	(i) ADSCs + PRP; (ii) ADSCs + HA	1 month	Both groups showed functional improvements in their disability, lameness on trotting, and pain on manipulation of the joints

(b)

Ref.	Study type	Pathology	Cell type and source	Injection/implantation	Study design	Number of patients	Follow-up	Results
Pak 2011, J Med Case Reports [50]	Case report	Knee OA	SVF; Abdominal area	1 injection	(i) ADSCs + PRP + HA + dexamethasone	2	3 months	Cartilage volume increased at MRI; Both improved function
Koh and Choi 2012, The Knee [19]	Comparative study	Knee OA	SVF; Infrapatellar fad pad	1 injection after debridement	(i) ADSCs + PRP; (ii) Only PRP (control)	Study group: 25; Control group: 25	16.4 months	Significant improvement in all clinical scores; Study versus control: n.s. at final follow-up, but study group had lower basal
Pak et al. 2013, BMC Musculoskeletal Disorders [20]	Case series	Knee OA	SVF; Abdominal area	1 injection	(i) ADSCs + PRP + HA	91	30 months	VAS improved 50–60%; No major complications
Pak et al. 2013, PLoS One [21]	Case series	Chondromalacia patellae	SVF; Abdominal area	1 injection	(i) ADSCs + PRP + HA	3	12 months	Pain improved: 50–70% at 1 m; 80–90% at 3 m
Koh et al. 2013, Knee Surg Sports Traumatol Arthrosc [51]	Case series	Knee OA	SVF; Buttocks	1 injection	(i) ADSCs + PRP	30	24 months	Significant clinical improvement 14/16 (87.5%) of 2nd look arthroscopy within 24 m improved or maintained cartilage status; Further clinical improvement 24 versus 12 m
Koh et al. 2013, Arthroscopy [49]	Case series	Knee OA	SVF; Infrapatellar fad pad	1 injection after debridement	(i) ADSCs + PRP	18	24.3 months	Significant improvement of the clinical and MRI scores at final follow-up
Bui et al. 2014, Biomedical Research and Therapy [55]	Case series	Knee OA	SVF; Abdominal area	1 injection	(i) ADSCs + PRP	21	6 months	Function improvement in all patients at 8.5 m. Increased cartilage thickness on MRI
Jo et al. 2014, Stem Cells [60]	Case series	Knee OA	Expanded; Abdominal area	1 injection	(i) Phase I: 3 doses of ADSCs; the low-, mid-, and high-dose group with 3 patients each; (ii) Phase II: 9 patients receiving the high dose of ADSCs	18	6 months	Clinical improvement and hyaline-like regenerative tissue only in high-dose group, without adverse events
Koh et al. 2014, Am J Sports Med [52]	Case series	Knee OA	SVF; Buttocks	1 injection after debridement	ADSCs local adherent technique	35 (37 knees)	12.7 months	Clinical improvement; 94% patients excellent or good satisfaction; 76% abnormal or severely abnormal repair tissue at 2nd look
Koh et al. 2014, Arthroscopy [53]	Comparative study	Knee OA	SVF; Buttocks	1 injection after debridement	(i) HTO + PRP + ADSCs (); (ii) HTO + PRP ()	44	24 months	Better clinical improvement in PRP + ADSCs group (some KOOS subgroups); Better tissue healing at 2nd look for PRP + ADSCs
Kim et al. 2015, Am J Sports Med [54]	Comparative study	Knee OA	SVF; Buttocks	1 injection after debridement	(i) ADSCs local adherent (); (ii) ADSCs on FG ()	54 (56 knees) second look	28.6 m; 12.3 m; (second look)	Overall clinical improvement; Comparable for both groups; Better ICRS scores at 2nd look for ADSC-FG group; Lower BMI and smaller size positively correlate with outcomes