Review Article

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

Table 1

Preclinical studies on animal model.

ā€‰Animal modelDefect typeDelivery methodADSCs processingStudy designResults

Nathan et al. 2003, Tissue Engineering [22]RabbitOsteochondral defectSurgical implantationExpanded homologous(i) ADSCs + fibrin
(ii) Periosteum MSCs + fibrin
(iii) Fibrin only
Better defect reconstruction in experimental groups than in control, with superior results for ADSCs

Masuoka et al. 2006, J Biomed Mater Res [41]RabbitOsteochondral defectSurgical implantationExpanded autologous(i) ADSCs + ACHMS-scaffold
(ii) ACHMS-scaffold alone
(iii) Empty defect
New regenerated hyaline-like cartilage only in the ADSCs group

Dragoo et al. 2007, Tissue Eng [36]RabbitOsteochondral defectSurgical implantationExpanded autologous(i) ADSCs + fibrin glue matrix
(ii) Empty defect
100% of defects healed in ADSCs group and only 8% in control group

Koga et al. 2008, Cell Tissue Res [24]RabbitOsteochondral defectSurgical implantationExpanded homologous(i) ADSCs
(ii) BMSCs
(iii) Synovium MSCs
(iv) Muscle MSCs
Great amount of cartilage matrix production in BMSCs and synovium MSCs compared to other groups
Low chondrogenic potential for ADSCs

Zhang et al. 2009, Chin J Traumatol [40]RabbitOsteochondral defectSurgical implantationExpanded homologous(i) ADSCs + calcium alginate gel
(ii) Calcium alginate gel alone
(iii) Empty defect
Complete defect healing only in the ADSCs group

Frisbie et al. 2009, J Orthop Res [27]HorseInduced OA (by arthroscopy)InjectiveExpanded autologous(i) ADSCs
(ii) BMSCs
(iii) Placebo (sham surgery)
No adverse treatment-related events
ADSCs decreased synovial fluid PDE G2
Overall improvement with cells n.s.

Cui et al. 2009, Biomaterials [37]PigOsteochondral defectSurgical implantationExpanded autologous chondrogenic-induced(i) ADSCs + PGA/PLA
(ii) PGA/PLA alone
Hyaline-like neo-cartilage
Well-integrated implant
Lack of cartilage repair for acellular group

Oliveira et al. 2010, J Orthop Res [45]RabbitOsteochondral defectSurgical implantationExpanded autologous chondrogenic-induced(i) Predifferentiated ADSCs + gellan gum (GG)
(ii) Not predifferentiated ADSCs + GG
(iii) Articular chondrocytes + GG
(iv) GG alone
(v) Empty defect
Good defect filling and integration with surrounding cartilage for cell-loaded constructs
Best results with predifferentiated ADSCs with GG

Im and Lee 2010, J Biomed Mater Res B Appl Biomater [23]RabbitOsteochondral defectSurgical implantationExpanded autologous(i) ADSCs + (PCL)/F127 scaffold
(ii) Scaffold alone
(iii) TGF-b2 + BMP-7 + scaffold
(iv) ADSCs + TGF-b2 + BMP-7 + scaffold
Incomplete cartilage healing for all groups
Better macroscopic score in growth factors groups compared to ADSCs alone

Li et al. 2011, Artif Cells Blood Substit Immobil Biotechnol [25]RabbitOsteochondral defectSurgical implantationExpanded autologous(i) ADSCs + DBM
(ii) BMSCs + DBM
(iii) Synovium MSCs + DBM
(iv) Periosteum MSCs + DBM
(v) Muscle MSCs + DBM
(vi) Empty defect
Good defect filling with new hyaline-like cartilage for each treatment group
BMSCs had best results for cartilage matrix synthesis, gross morphology, and histology

Toghraie et al. 2011, The Knee [32]RabbitInduced OA
ACL transection
(ACLT)
InjectiveExpanded homologous(i) ADSCs from infrapatellar fat pad
(ii) Control (medium only)
Better cartilage quality, lower subchondral changes, and lower OA features for ADSCs group than controls

Toghraie et al. 2012, Arch Iran Med [33]RabbitInduced OA
(ACLT)
InjectiveExpanded homologous(i) ADSCs from subcutaneous fat
(ii) Control (medium only)
Improved cartilage quality for ADSC group compared to control

Lee and Im 2012, Biomaterials [43]RatInduced OA
(ACLT)
InjectiveExpanded transduced SOX-trio genes autologous(i) ADSCs transduced with SOX-trio genes + fibrin gel
(ii) ADSCs transfected with empty vector
(iii) Fibrin gel alone
Decrease of OA progression Decrease of OA progression for ADSCs in fibrin gel group
Surgical implantationGood hyaline cartilage-like tissue regeneration for the transfected ADSCs/fibrin gel group
Incomplete healing and fibrous tissue in both controls

Ter Huurne et al. 2012, Arthritis Rheum [34]MouseInduced OA (collagenase injection)InjectiveExpanded autologous(i) ADSCs + 4% mouse albumin
(ii) Only 4% mouse albumin
Inhibition of OA progression in early stage of OA, whereas no effects with injections in late OA stage

Xie et al. 2012, Biomaterials [44]RabbitOsteochondral defectSurgical implantationExpanded homologous(i) ADSCs + PRP
(ii) BMSCs + PRP
(iii) PRP alone
(iv) Empty defect
(v) Sham treatment
Better repair for cell + PRP groups versus PRP alone
BMSCs higher chondrogenic differentiation
ADSCs differentiate into mature chondrocytes

Cao et al. 2012, J Biomed Biotechnol [58]RabbitOsteochondral defectSurgical implantationExpanded autologous(i) ADSCs-bBMPs-bilayered construct
(ii) bBMPs-bilayered construct
(iii) Empty defect
Better defect healing and integration with host tissue in the ADSCs-bBMPs-bilayered construct group

Desando et al. 2013, Arthritis Res Ther [35]RabbitInduced OA
(ACLT)
InjectiveExpanded autologous(i) 2 mln ADSCs + 4% rabbit serum
(ii) 6 mln ADSCs + 4% rabbit serum
(iii) 4% rabbit serum alone
(iv) No treatment
(v) Sham group
Decrease of OA progression in the study groups compared to controls
Best results for implanted 2 mln ADSCs

van Pham et al. 2013, Stem Cell Res Ther [29]MouseInduced OA (needle disruption)InjectiveExpanded human ADSCs(i) ADSCS + 15% PRP
(ii) ADSCS + 10% FBS
(iii) PBS only
(iv) No treatment, no defect
Tendency for better cartilage repair improvement for cell-transplanted groups compared to PBS group, significantly better results for PRP-pretreated ADSCs on all parameters

van Pham et al. 2013, J Med Engineering [30]MouseInduced OA (needle disruption)InjectiveHuman SVF(i) ADSCs + PRP
(ii) Only PBS
(iii) No treatment, no defect
Significant improvement in articular cartilage regeneration for PRP-pretreated ADSCs compared to PBS control
No adverse events, high safety

Jurgens et al. 2013, Bio Research [31]GoatOsteochondral defectSurgical implantationExpanded versus SVF autologous(i) Expanded ADSCs + collagen I/III
(ii) Concentrated ADSCs + collagen I/III
(iii) Collagen I/III alone
Good tissue regeneration in all groups with tendency towards better results in cell-treated groups and in particular for concentrated ADSCs
No adverse events

Zhang et al. 2013, Acta Biomaterialia [39]RabbitOsteochondral defectSurgical implantationExpanded chondrogenic-induced autologous(i) Predifferentiated ADSCs + PLGA/CHI
(ii) PLGA/CHI alone
Good tissue regeneration, similar to healthy cartilage, well integrated with surrounding tissue in ADSCs/scaffold group compared to scaffold alone

Shi et al. 2013, Arthroscopy [42]RabbitOsteochondral defectSurgical implantationExpanded and transfected autologous(i) BMP-4 transfected ADSCs + PLLGA
(ii) Nontransfected ADSCs + PLLGA
(iii) PLLGA alone
Better improvement in chondrogenesis in vivo for the transfected ADSCs group with respect to untransfected and scaffold alone

Gong et al. 2014, Tissue Eng part A [38]PigOsteochondral defectSurgical implantationExpanded chondrogenic-induced autologous(i) ADSCs + PGA/PLA
(ii) PGA/PLA alone
Successful new cartilage
Graft remodeling between 3 and 6ā€‰m
Proteomic analysis detected differences versus native cartilage

Wang et al. 2014, Genet Mol Res [59]RabbitOsteochondral defectSurgical implantationExpanded homologous(i) ADSCs preseeded ACM
(ii) ACM only
(iii) Empty defect
Chondral tissue with hyaline features in ADSC-ACM group, with type II coll., fibrous tissue in ACM only

Ude et al. 2014, PLoS One [26]SheepInduced OA
(ACLT)
InjectiveExpanded chondrogenic-induced autologous(i) ADSCs
(ii) BMSCs
(iii) Control
ADSCs had higher cell proliferation and BMSCs had better chondrogenic inductions and gene expressions
ICRS score n.s. ADSCs versus BMSCs