Table 1.
Chronological list of publications of MSC application for cartilage repair.
| Author/year | Sample size/gender | Age (mean or average) | Type of cartilage lesions | Stages of OA | Stem cell source/amount | Mode of delivery | Co-treatment | Control groups | Longest follow-up time point | Assessments | Ref | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | de Windt TS/2017 | 10 (8M, 2F) | 18–45 | Symptomatic isolated cartilage defect (femoral condyle/trochlea) | Modified Outerbridge Grade 3 or 4 | Allogeneic bone marrow-derived MSCs/NS | Single defect site-specific implantation | 10 or 20% autologous chondrons | Nil | 12 months | KOOS, VAS, EQ5D, MRI, second-look arthroscopy, histology (biopsy) | [42] |
| 2 | Pers YM/2016 | 18 (8M, 10F) | 50–75 | Knee OA | KL: 3 or 4 | Adipose-derived MSCs/Low: 2 × 106; Mid: 10 × 106; High: 50 × 106 | Single intra-articular injection | Nil | Nil | 6 months | Primary outcome: Safety of the dose-escalation protocol Secondary outcome: WOMAC, VAS, PGA, SAS, KOOS, histology (biopsy) |
[48] |
| 3 | Koh YG/2016 | 80 (30M, 50F) | 18–50 | Symptomatic cartilage defect (≥3 cm2) on femoral condyle | ICRS: 3 or 4 | Adipose-derived MSCs/5 × 106 | Single defect site-specific implantation | Microfracture; fibrin glue | Microfracture | 24 months | MRI, Lysholm score, KOOS, VAS, second-look arthroscopy and histology (biopsy) | [46] |
| 4 | Fodor PB/2016 | 6 (1M, 5F) | 51–69 | Knee OA | KL: 1 to 3 | Adipose-derived stromal vascular cells/14 × 106 | Single intra-articular injection | Nil | Nil | 12 months | WOMAC, VAS, ROM, TUG, MRI | [43] |
| 5 | Davatchi F/2016 | 4 (2M, 2F) | 54–65 | Knee OA | KL: 2 or 3 | Bone marrow-derived MSCs/8–9 × 106 | Single intra-articular injection | Glucosamine was permitted if the patients was taking it before being enrolled. | Nil | 60 months | Standing knee X-ray, VAS, ROM, walking time for pain to appear. | [41] |
| 6 | Akgun I/2015 | 14 (8M, 6F) | 18–46 | Isolated full thickness knee chondral defect >2 cm2 | KL: 1 or 2 | Autologous synovium-derived MSCs/4 × 106 | Implantation of cells preloaded collagen membrane into the debrided site | Type I/III collagen membrane (2 × 2 cm) | Matrix-induced autologous chondrocyte implantation | 24 months | Primary outcome: pain assessment and KOOS Secondary outcome: clinical knee examination and MRI |
[57] |
| 7 | Vega A/2015 | 30 (13M, 17F) | 36–73 | Knee OA | KL: 2 to 4 | Allogeneic bone marrow-derived MSCs/40 × 106 | Single intra-articular injection | Nil | Single dose of HA | 12 months | VAS, WOMAC, Lequesne, SF-12, MRI | [51] |
| 8 | Jo CH/2014 | Phase I: 9 patients (n = 3 each group) | 18–75 | Knee OA | KL: 2 to 4 | Adipose-derived stromal cells/Low: 1 × 107; Mid : 5.0 × 107; High : 1 × 108 cells | Single intra-articular injection | Nil | Nil | 6 months | Primary outcomes: Safety and WOMAC Secondary outcomes: Clinical (VAS & KSS); Radiological (X-ray and MRI); Arthroscopic (Size and ICRS), and Histology (biopsy) |
[44] |
| Phase II: 12 patients (including 3 (high dose) from phase I | Adipose-derived stromal cells/1 × 108 cells | |||||||||||
| 9 | Vangsness Jr CT/2014 | 55 (35M, 20F) | 18–60 | Patient underwent partial medial meniscectomy | Not specified | Allogeneic bone marrow-derived MSCs/Group A: 50 × 106; Group B: 150 × 106 | Superolateral knee injection | Injection given 7–10 days after partial medial meniscectomy | Vehicle control (sodium hyaluronate, human serum albumin and PlasmaLyte A) | 24 months | Safety assessment, serological measurement of immune cell markers, MRI, VAS, Lysholm Knee Scale Score | [50] |
| 10 | Wong KL/2013 | 56 (29M, 27F) | 18–55 | Uni-compartmental OA knee (medial) & genu varum | ICRS: 2 to 4 | Bone marrow-derived MSCs/1.46 ± 0.29 × 107 cells | Intra-articular injection | MSCs injection in conjunction with microfracture & High tibial osteotomy; MSCs in HA (2 mL); followed by 2 extra doses of 2 mL HA injection repeated at weekly intervals for all patients | HA | 24 months | Primary Outcome: IKDC Secondary Outcome: Tegner and Lysholm clinical scores; MOCART |
[52] |
| 11 | Orozco L/2013 | 12 (6M, 6F) | 49 ± 5 | Knee OA | KL: 2 to 4 | Bone marrow-derived MSCs/40 × 106 cells | Intra-articular injection | Ringer lactate, 0.5% human albumin and 5 mM glucose | Nil | 12 months | VAS, WOMAC, Lequesne, MRI, | [47] |
| 12 | Saw KY/2013 | 49 (17M, 32F) | 18–50 | Focal Chondral lesion | ICRS: 3 or 4 | Autologous peripheral blood progenitor cells/NS | Intra-articular injection | PBSC + HA; 5 weekly injections 1 week after surgery followed by 3 additional injections weekly intervals at 6 months | HA | 24 months | IKDC; MRI; second-look arthroscopy; histology (biopsy) | [49] |
| 13 | Koh YG/2013 | 18 (6M, 12F) | 54.6 | Knee OA | ICRS: Grade 3 or 4KL: Grade 3 or 4 | Infrapatellar fat pad MSCs/1.18 × 106 | IA injection - lateral approach | Arthroscopy debridement; MSCs in PRP (Avg 1,280,000/μL platelets); PRP injection every 7 days for 2 weeks; CaCl2 added to PRP for activation | Nil | 26 months | Lysholm score; Tegner activity scale; VAS; MRI | [53] |
| 14 | Koh YG/2012 | 25 (8M, 17 F) | 54.1 | Knee OA | ICRS: Grade 3 or 4KL: Grade 3 or 4 | Infrapatellar fat pad MSCs/1.89 × 106 | IA injection - lateral approach | Arthroscopy debridement; MSCs in PRP (Avg 1,280,000/μL platelets); PRP injection every 7 days for 2 weeks; CaCl2 added to PRP for activation | PRP | 18 months | Lysholm score; Tegner activity scale; VAS | [45] |
| 15 | Saw KY/2011 | 5 (1M, 4F) | 39.4 | Focal Chondral lesion | ICRS 3 or 4 | Autologous peripheral blood progenitor cells/NS | Intra-articular injection | Arthroscopic subchondral drilling; 5 weekly injections 1 week after surgery; 3 additional injections of either HA or PBSC + HA weekly intervals 6 months after surgery | Nil | 26 months | Second look arthroscopy; Histology (H&E, Safranin O, IHC) | [54] |
| 16 | Nejadnik H/2010 | 72 (38M, 34F) | 43.25 | Symptomatic chondral lesion | Lesion grade 3 or 4 | Autologous bone marrow derived MSCs/NS | Implantation upon autologous periosteal patch | Fibrin glue | First-generation autologous chondrocyte implantation | 24 months | ICRS cartilage injury evaluation package, IKDC, Lysholm score; Tegner activity scale | [58] |
| 17 | Davatchi F/2011 | 4 (2M, 2 F) | 57.75 | Bilateral OA | Nil | Autologous bone marrow derived MSCs from iliac crest/8 or 9 × 106 | Intra-articular injection | Saline with 2% human serum albumin | Nil | 6 months | X-rays; Clinical; VAS | [55] |
| 18 | Wakitani/2002 | 24 (9M, 15F) | 63 | Medial unicompartmental OA | Ahlback changes: Stage 1–2; Outerbridge stage 4 lesion on the tibial plateau and femoral condyle | Autologous bone marrow derived MSCs from iliac crest/NS | Implantation of collagen cell sheets | High tibial osteotomy; Gel-cell composite; Covered with autologous periosteum | Cell free | 95 weeks | Arthroscopic photography; Histological samples (cell morphology); Clinical evaluation (Pain Function Range of motion Muscle strength Flexion deformity Instability Subtraction etc) | [56] |
EQ5D = EuroQoL 5-Dimension Health Questionnaire; F = female; HA = hyaluronic acid; H&E = haematoxylin and eosin staining; ICRS = International Cartilage Repair Society score; IHC = immunohistochemistry; IKDC = International Knee Documentation Committee; KL = Kellgren–Lawrence Scale; KOOS = Knee injury and Osteoarthritis Outcome Scoring; KSS = Knee Society Clinical Rating System score; Lequesne = Lequesne algo-functional indices; M = male; MOCART = Magnetic Resonance Observation of Cartilage Repair Tissue score; MRI = magnetic resonance imaging; MSC = mesenchymal stem cell; NS = not specified; OA = osteoarthritis; PBSC = peripheral blood stem cell; PGA = Patient Global Assessment; PRP = platelet-rich plasma; ROM = range of motion; SAS = Short Arthritis Assessment Scale; SF-12 = short form-12 life quality questionnaire; TUG = timed up-and-go; VAS = visual analogue scale for pain; WOMAC = Western Ontario and McMaster Universities Arthritis Index.