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Table 2 Clinical studies assessing mesenchymal stem cell-based treatment of traumatic chondral and osteochondral defects

From: Mesenchymal stem cells in the treatment of traumatic articular cartilage defects: a comprehensive review

Scientific publication Study type Subject details Defect characteristics Implanted/injected construct Follow-up period Key findings
Kuroda et al. (2007) [82] Case report: level IV evidence 1 M (age 31 y) 1 medial femoral condyle chondral defect (6.0 cm2) from trauma Implantation of isolated BM-derived MSCs within porcine type I collagen gel on a collagen scaffold; covered by a periosteal flap 12 months Arthroscopic: firm, smooth repair tissue. Histologic: hyaline-like cartilage covered superficially by fibrous tissue. MRI: focal chondral and subchondral irregularities. Clinical: return to previous level of activity
Wakitani et al. (2007) [88] Case series: level IV evidence 3: 2 M, 1 F (age 32-45 y) 5 femoral trochlea (0.7-4.2 cm2) and 4 patella chondral defects (1.0-1.7 cm2); defects in 2/3 participants from trauma Implantation of isolated BM-derived MSCs within bovine type I collagen gel on a porcine collagen scaffold; covered by a periosteal flap or synovium; adjunctive subchondral drilling 18 months Arthroscopic: firm, smooth tissue. Histologic: atypical cartilage. MRI: complete coverage of defects but quality unclear. Clinical: improvement of symptoms and return to work; IKDC improvement
Giannini et al. (2009) [80] Case series: level IV evidence 48: 27 M, 21 F (mean age 28.5 ± 9.5 y) 48 talar dome osteochondral defects (2.07 ± 0.48 cm2); 35 from trauma; previous MFX, debridement or ACI in 15 Implantation of BMDCs suspended within collagen/platelet paste or seeded on HA (Hyaff-11) scaffold 24-35 months Arthroscopic: smooth tissue in some, hypertrophic in others; all integrated with firmness of native cartilage. Histologic: mixed with some hyaline quality. MRI: newly formed tissue in all lesions. Clinical: improvement in AOFAS scores with time and return to sports with no difference between scaffold types; worse outcomes with previous surgery
Buda et al. (2010) [81] Case series: level IV evidence 20: 12 M, 8 F (mean age 28.5 ± 9.5 y) 16 medial femoral condyle and 6 lateral condyle osteochondral defects (no area provided); 18 traumatic and 2 OCD defects Implantation of BMDCs seeded on a HA (Hyalofast) scaffold supplemented with platelet-rich fibrin; adjunctive meniscus repair or debridement, ACL-R, or HTO 29 ± 4.1 months Histologic: collagen II noted throughout repair tissue with focal proteoglycan content consistent with hyaline-like cartilage. MRI: variable signal intensity that correlated with KOOS score. Clinical: improvement in IKDC and KOOS scores post-operatively
Giannini et al. (2010) [90] Prospective comparative study: level III evidence 81: 47 M, 34 F (mean age 30 ± 8 y); 25 BMDC; 10 ACI; 46 MACI 81 talar dome osteochondral defects (>1.5 cm2) from trauma Implantation of BMDCs seeded on a HA (Hyaff-11) scaffold supplemented with platelet-rich fibrin 59.5 ± 26.5 months Arthroscopic: good defect coverage. Histologic: hyaline-like cartilage noted. MRI: complete integration in 76% and homogenous tissue in 82% of all cases with hypertrophy in 3 BMDC and 2 ACI patients. Clinical: improvement in AOFAS scores after surgery with no difference between BMDC-scaffold implants, ACI and MACI; lower overall cost for BMDC transplantation compared to ACI/MACI
Haleem et al. (2010) [83] Case series: level IV evidence 5: 4 M, 1 F (mean age 25.4 y) 5 femoral condyle chondral defects (3-12 cm2); 2 traumatic, and 3 OCD defects (1 OA from neglected OCD) Implantation of isolated BM-derived MSCs within platelet-rich fibrin glue; covered by a periosteal flap 12 months Arthroscopic: smooth tissue. MRI: complete defect filling with good congruity in 3/5 patients. Clinical: improvement in Lysholm and RHSSK scores with return to sports; worse outcomes in 1 patient with pre-operative OA
Nejadnik et al. (2010) [84] Prospective comparative study: level III evidence 72: 38 M, 34 F (mean age 44.0 ± 11.4 y), 36 MSCs; 36 ACI 13 patella, 4 femoral trochlea, 12 femoral condyle, and 7 multiple knee chondral defects (4.6 ± 3.5 cm2); 14 traumatic, 20 OA and 2 other defects Implantation of isolated BM-derived MSCs; covered by a periosteal flap; adjunctive partial meniscectomy, patellar realignment, ACL-R, or HTO 24 months Arthroscopic: smooth tissue in most cases. Histologic: aggrecan and collagen II content consistent with hyaline cartilage. Clinical: greater improvement in SF-36 Physical Role Functioning in MSCs versus chondrocytes; equivalent IKDC, Tegner and Lysholm score improvement following both MSC and chondrocyte transplantation; superior outcomes in males versus females
Gobbi et al. (2011) [89] Case series: level IV evidence 15: 10 M, 5 F (mean age 48 y, range 32-58 y) 7 patella, 6 femoral trochlea, 4 medial tibial plateau, 6 medial femoral condyle, and 1 lateral condyle chondral defects (9.2 ± 6.3 cm2); all defects from trauma; 6 patients had multiple defects Implantation of BMDCs mixed with batroxobin (Plateltex Act) to produce a clot; covered by a type I/III collagen matrix (Chondro-Gide); adjunctive ACL-R, HTO, patellar realignment 24-38 months Arthroscopic: smooth, integrated tissue in all cases; no hypertrophy. Histologic: variability with properties of hyaline and fibrocartilage. MRI: complete defect filling in 80%, integration in 93%, and no hypertrophy in all patients. Clinical: improvement in all scores (VAS, KOOS, Tegner, Marx, IKDC and Lysholm) following surgery; patients with single lesions and smaller lesions had better outcomes
Kasemkijwa-ttana et al. (2011) [85] Case series: level IV evidence 2 M (age 24-25 y) 2 lateral femoral condyle chondral (2.2-2.5 cm2) Implantation of isolated BM-derived MSCs seeded on a type I collagen scaffold supplemented with fibrin glue; covered by a periosteal flap; adjunctive ACL-R, meniscal repair 30-31 months Arthroscopic: good defect fill, integration and firmness. Clinical: significant improvement in IKDC score and KOOS post-operatively
Saw et al. (2011) [98] Case series: level IV evidence 5: 1 M, 4 F (mean age 39.4 y, range 19-52 y) 3 focal defects: 1 lateral femoral condyle (2 cm2), 1 patella (8.8 cm2), 1 femoral trochlea (0.5 cm2); 2 OA defects Injection of peripheral blood-derived MSCs with HA weekly (×5) starting 1 wk after subchondral drilling; adjunctive HTO or lateral patellar release; pre-injection GCSF 10-26 months Arthroscopic: good filling in focal defects; range from devoid areas to smooth repair tissue in OA defects. Histologic: intense proteoglycan staining; type I collagen in superficial area with predominance to type II collagen in deep area; chondrocytes in subchondral drill holes
Gigante et al. (2012) [86] Case report: level IV evidence 1 M (age 37 y) 1 medial femoral condyle chondral defect (3 cm2) from trauma Implantation of BMDCs within fibrin glue (Tisseel) and coverage with a collagen membrane (MeRG) after arthroscopic MFX (CMBMC) 24 months MRI: good defect filling with tissue that was isointense relative to native cartilage; no signs of bone edema. Clinical: return to activity and asymptomatic
Enea et al. (2013) [87] Case series: level IV evidence 9: 5 M, 4 F (mean age 48 ± 9 y) 6 medial femoral condyle and 3 lateral condyle chondral defects (2.6 ± 0.5 cm2); previous meniscectomy, debridement or ACL-R Implantation of BMDCs within fibrin glue and coverage with a PGA-HA membrane (Chondro-tissue) after arthroscopic MFX (CMBMC); adjunctive meniscectomy, osteochondral fixation, or trochlea resurfacing 22 ± 2 months Arthroscopic: 1 normal, 3 nearly normal and 1 abnormal on ICRS CRA. Histologic: hyaline-like cartilage repair tissue. MRI: complete defect filling in all; mild subchondral irregularities in all; hypertrophy in 1 patient. Clinical: improvement in IKDC and Lysholm scores compared with pre-operative scores; no change in Tegner score from pre-injury; one failure
Giannini et al. (2013) [91] Case series: level IV evidence 49: 27 M, 22 F (mean age 28.1 ± 9.5 y) 49 talar dome osteochondral defects (2.2 ± 1.2 cm2); 36 traumatic defects with unknown etiology in others; previous debridement, MFX, ACI, or BMDCs in 17 Implantation of BMDCs within collagen/platelet paste or seeded on HA (Hyaff-11) scaffold supplemented with platelet gel 48 months MRI: complete defect filling in 45%, hypertrophy in 45%, integration in 65%, subchondral disruption in 65% of cases; 78% of repair area had hyaline quality. Clinical: improvement in AOFAS scores - maximal value at 24 months; decreased at 36-48 months; decreased AOFAS associated with fibrocartilage quality; return to pre-injury sports in 78%
Saw et al. (2013) [29] RCT: level II evidence 49: 17 M, 32 F (mean age 38 ± 7 y); 25 MSC + HA; 24 HA 49 chondral defects of the knee (57% patella, 29% trochlea, 12% femoral condyle, and 8% tibial plateau) Injection of peripheral blood-derived MSCs and HA weekly (×5) starting 1 wk after subchondral drilling and then weekly (×3) at 6 months; pre-injection GCSF 24 months Arthroscopic: smooth defect filling. Histologic: ICRS II score was significantly better in MSC + HA group. MRI: improved cartilage morphology, defect filling and integration in MSC + HA group. Clinical: improvement in IKDC scores with no difference between MSC + HA and HA
  1. ACI, autologous chondrocyte implantation; ACL-R, anterior cruciate ligament reconstruction; AOFAS, American Orthopaedic Foot and Ankle Society; BM, bone marrow; BMDC, bone marrow-derived cell; CMBMC, covered microfracture and bone marrow concentrate; CRA, Cartilage Repair Assessment (arthroscopy); F, female; GCSF, granulocyte colony stimulating factor; HA, hyaluronic acid; HTO, high tibial osteotomy; ICRS, International Cartilage Repair Society; IKDC, International Knee Documentation Committee; KOOS, Knee Injury and Osteoarthritis Outcome Score; M, male; MACI, matrix-associated autologous chondrocyte implantation; MFX, microfracture; MRI, magnetic resonance imaging; MSC, mesenchymal stem cell; OA, osteoarthritis; OCD, osteochondral dissecans; PGA-HA, polyglycolic acid-hyaluronic acid; RCT, randomized controlled trial; RHSSK, Revised Hospital for Special Surgery knee; SF-36, Short Form-36; VAS, Visual Analogue Scale; wk, week(s); y, year(s).