Background
Stem cell properties | |
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• They are unspecialized (“blank slates” that can become specific types of cells). | |
• They can develop into specialized cell types (cells that do specific work in the body). | |
• They are capable of surviving over long periods and divide to make additional stem cells. |
Clinical trial phases (http://www.nlm.nih.gov/services/ctphases.html) | |
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Phase I: Safety Studies or First-In-Man. Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects. | |
Phase II: Uncontrolled Efficacy Studies. The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety. | |
Phase III: Randomised Clinical Trials. The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely. | |
Phase IV: Post-Market Surveillance. Studies are done after the drug or treatment has been marketed to gather information on the drug’s effect in various populations and any side effects associated with long-term use. |
Main text
Search methodology
Results
In vitro studies
Cell species | No. of studies | References | Cell Source | No. of studiesa
| References |
---|---|---|---|---|---|
Human | 73 | Bone marrow | 62 | ||
Rabbit | 17 | Adipose | 36 | ||
Bovine | 5 | Synovium | 9 | ||
Rat/mouse | 5 | Umbilical cord blood | 3 | ||
Porcine | 3 | Commercial cell line | 2 | ||
Equine | 3 | Placental | 2 | ||
Goat | 1 | [244] | Embryonic | 1 | [216] |
Ovine | 2 | Not stated | 0 | ||
Not stated | 1 | [267] |
Number of studies using types of scaffold | ||||
Natural | Synthetic | Hybrid | Growth factor combined | None used |
47 | 14 | 22 | 6 | 29 |
Scaffold | No. of studies | References | ||
Types of scaffolds used | ||||
Natural scaffolds | ||||
Type I collagen hydrogel | 6 | |||
Agarose hydrogel | 4 | |||
Alginate bead | 3 | |||
Fibrin hydrogel | 3 | |||
Silk fibroin | 3 | |||
Chitosan microspheres | 2 | |||
Hyaluronic acid | 2 | |||
Cartilage-derived matrix | 2 | |||
K-carrageenan | 2 | |||
Chitosan | 2 | |||
Hyaluronic acid hydrogel | 2 | |||
Gelatin-based scaffold | 2 | |||
Devitalised cartilage ECM | 1 | [220] | ||
Bead in bead alginate polysaccharide capsules | 1 | [221] | ||
Atelocollagen gel | 1 | [225] | ||
Fibrin disk | 1 | [254] | ||
Methacrylated hyaluronic acid | 1 | [164] | ||
Gelatin microspheres | 1 | [260] | ||
Decellularised cell matrix | 1 | [191] | ||
Collagen type I microspheres | 1 | [52] | ||
Alginate microbeads | 1 | [266] | ||
Alginate disks | 1 | [270] | ||
Platelet rich plasma | 1 | [242] | ||
Free oligosaccharide chondroitin sulphate C | 1 | [205] | ||
Collagen type I sponge | 1 | [237] | ||
3D printed chitosan | 1 | [181] | ||
Synthetic scaffolds | ||||
Polycaprolactone | 3 | |||
PLGA | 3 | |||
Polylactic acid | 2 | |||
PVA | 1 | [244] | ||
PGA | 1 | [178] | ||
Poly-DL-lactide-co-glycolide | 1 | [194] | ||
Polylactide-co-caprolactone | 1 | [214] | ||
GFOGER modified PEG hydrogel | 1 | [183] | ||
OPF hydrogel | 1 | [240] | ||
Hybrid scaffolds | ||||
Fibrin–polurethane hydrogel | 4 | |||
Esterified hyaluronan and gelatin polymer | 2 | |||
TruFit CB (PLGA, calcium sulphate and polycolide) | 1 | [187] | ||
PCL–HA bilayer | 1 | [243] | ||
PEGDG–crosslinked hyaluronic acid | 1 | [202] | ||
Polylactic acid–alginate | 1 | [232] | ||
Sodium alginate–hyaluronic acid | 1 | [189] | ||
Chitosan–collagen type I | 1 | [258] | ||
Polyvinylalcohol–polycaprolactone | 1 | [246] | ||
Tricalcium phosphate-collagen-hyaluronan | 1 | [180] | ||
Poly-L-lactic acid–hydroxyapatite | 1 | [215] | ||
Collagen type I–polylactic acid | 1 | [217] | ||
Polylactic acid–polyglycolic acid with fibrin | 1 | [261] | ||
Collagen–polyglycolic acid | 1 | [252] | ||
Chondroitin sulphate C–collagen type II | 1 | [236] | ||
Fibrin hydrogel with chondroitin sulphate | 1 | [263] | ||
Chitosan-demineralised bone matrix | 1 | [239] | ||
Alginate foam-chondroitin sulphate | 1 | [170] | ||
Growth factor combined with scaffolds | ||||
TGF-β1-loaded microspheres with chitosan microspheres | 1 | [262] | ||
TGF-β1 releasing chitosan-collagen hydrogel | 1 | [174] | ||
PEOT/PBT TGF-β1 loaded scaffolds | 1 | [173] | ||
TGF-β1-activated chitosan/gelatin | 1 | [249] | ||
PLGA nanospheres with TGF-β1 | 1 | [172] | ||
TGF-β1 loaded Gelatin Microspheres | 1 | [175] |
Growth factor | No. of studies (%) | References | Growth factor | No. of studies (%) | References |
---|---|---|---|---|---|
TGF-β1 | 48 (44%) | SOX-5 | 1 (1%) | [204] | |
TGF-β3 | 32 (29%) | SOX-6 | 1 (1%) | [204] | |
BMP-2 | 13 (12%) | WNT3A | 1 (1%) | [171] | |
FGF | 9 (8%) | IL-1 | 1 (1%) | [197] | |
IGF-1 | 7 (6%) | EGF | 1(1%) | [193] | |
BMP-6 | 7 (6%) | OP-1 | 1 (1%) | [222] | |
TGF-β2 | 4 (4%) | AA2P | 1 (1%) | [266] | |
GDF-5 | 3 (3%[ | IL-10 | 1 (1%) | [178] | |
SOX-9 | 2 (2%) | TNFα | 1 (1%) | [178] | |
BMP-4 | 2 (2%) | PRP | 1 (1%) | [242] | |
DEX | 2 (2%) | IWP2 | 1 (1%) | [171] | |
BMP-7 | 1 (1%) | [219] | None | 15 (14%) | |
PDGF | 1 (1%) | [202] |
Type of techniques | No. of studies (%) | References |
---|---|---|
Histology | 87 (79%) | |
Immunohistochemistry | 78 (71%) | |
qPCR | 70 (64%) | |
Biochemical analysis | 64 (58%) | |
Imaging (confocal, SEM, TEM) | 24 (22%) | |
Mechanical testing | 15 (14%) |
Animal studies (pre-clinical)
Scaffold type | No. of studies | References |
---|---|---|
No Scaffold | 19 (17%) | |
Poly (lactide-co-glycoside) PLGA | 17 (16%) | |
Fibrin/Fribrin glue | 11 (9%) | |
Hydrogel | 9 (8%) | |
Collagen | 9 (8%) | |
Hyaluronic acid | 7 (6%) | |
Alginate beads | 4 (3%) | |
Tissue membrane | 4 (3%) | |
Polyglycolic acid | 3 (3%) | |
PGA/PLA | 3 (3%) | |
Hylauronan crosslinked matrix | 2 (2%) | |
Poly-L-lactide-co-caprolactone | 2 (2%) | |
Polycaprolactone cartilage (PCL) | 2 (2%) | |
Animal-origin osteochondral plug scaffold | 2 (2%) | |
Chitosan microspheres and fibrin glue | 1 (<1%) | [60] |
Gel carries (collagen/HA/Fibrogen) | 1 (<1%) | [71] |
Polychoxanone/poly(vinyl alcholo) PDO/PVA | 1 (<1%) | [302] |
Cartilage aggregate | 1 (<1%) | [306] |
Collagen/glycosaminoglycan porous titanium biphasic scaffold | 1 (<1%) | [151] |
Articular chondrocyte seeded matrix associated autologous chondrocyte transplant (MACT) | 1 (<1%) | [313] |
MSC-ADM (accellulo-dermal matrix) | 1 (<1%) | [319] |
Hyaff-11 scaffold | 1 (<1%) | [295] |
Porous-gelatin-chonroitin hyaluronate | 1 (<1%) | [291] |
Bone protein 7 PCL | 1 (<1%) | [66] |
Human acellular amniotic membrane | 1 (<1%) | [307] |
Pluronic-F 127 | 1 (<1%) | [102] |
Tricalcium phosphate | 1 (<1%) | [315] |
Agarose | 1 (<1%) | [311] |
GCH-GCBB | 1 (<1%) | [93] |
ACHMS (atelocollagen honeycomb-shaped membrane) | 1 (<1%) | [58] |
Magnet | 1 (<1%) | [310] |
Human cartilage extra cellular matrix 3D porous acellular | 1 (<1%) | [67] |
Growth factor | No. of studies | References |
---|---|---|
TGF-β3/1/2 | 17 (15%) | |
CDMP–1 | 2 (2%) | |
FGF-2 | 2 (2%) | |
Ad-hTGF-B1 | 1 (<1%) | [321] |
AdBMP–2 | 1 (<1%) | [78] |
chABC | 1 (<1%) | [74] |
PRP | 1 (<1%) | [75] |
Gene modified MSCs (gene modification to BcL-xL gene) | 1 (<1%) | [299] |
hiGF-1-DNA | 1 (<1%) | [101] |
AdIGF–1 | 1 (<1%) | [78] |
rHuBMP–2 | 1 (<1%) | [82] |
Ham-F-12 | 1 (<1%) | [303] |
NaO11 | 1 (<1%) | [277] |
NSC23766-Rac1 inhibitor | 1 (<1%) | [60] |
Outcome score | No. of studies using the score (%) | References |
---|---|---|
Histology scores | 111 (100%) | |
International Cartilage Repair Society Score | 26 (23%) | |
Wakitani score | 21 (19%) | |
O’Driscoll score | 2018% | |
Functional scores/mechanical | 11 (10%) | |
MRI scores | 5 (5%) | |
Arthroscopy scores | 5 (5%) | |
Macroscopic osteoarthritis score | 3 (3%) | |
Pineda score | 3 (3%) | |
Schreiber score | 2 (2%) | |
Britternberg score | 2 (2%) | |
Slochagg score | 1 (<1%) | [300] |
Moran score | 1 (<1%) | [64] |
Gill score | 1 (<1%) | [95] |
Analysis used | No. of studies (%) | References |
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Hyaline-like cartilage | 88 (79%) | |
Collagen type II | 84 (76%) | |
Cluster Chondrocytes | 34 (31%) | |
Glycosaminoglycan | 40 (36%) | |
Genes | 22 (20%) | |
Proteoglycan | 8 (7%) |
Human studies (clinical)
Category | No. of studies (total 28) | References |
---|---|---|
Phases of clinical studies | ||
Pilot/feasibility study incl. case report | 15 (54%) | |
Phase 1 (safety assessment) | 8 (26%) | |
Phase 2 (efficacy assessment) | 8 (26%) | |
Phase 3 (large scale efficacy assessment through a multi-centre RCT) | 0 (0%) | – |
Phase 4 (post-market surveillance) | 0 (0%) | – |
Category | No. of studies | References |
---|---|---|
Cell source | ||
Bone marrow | 22 (71%) | |
Adipose | 5 (16%) | |
Peripheral blood | 2 (6%) | |
Synovium | 2 (6%) | |
Cell delivery | ||
Arthroscopic implantation | ||
Hyaluronic acid membrane | 2 (6%) | |
Hyaluronic acid with fibrin glue or platelet gel | 2 (6%) | |
Polyglycolic acid/hyaluronan | 2 (6%) | |
Collagen with platelet gel | 1 (3%) | [116] |
Fibrin glue | 1 (3%) | [108] |
HYAFF 11 scaffold | 1 (3%) | [132] |
Acetate Ringer solution | 1 (3%) | [133] |
Unspecified | 1 (3%) | [107] |
Intra-articular injection | ||
PBS only | 2 (6%) | |
PBS with HA | 2 (6%) | |
Autologous serum | 2 (6%) | |
Ringer lactate solution | 3 (10%) | |
PBS with serum albumin | 1 (3%) | [105] |
HA and PRP | 1 (3%) | [106] |
PRP | 1 (3%) | [114] |
Commercial serum | 1 (3%) | [109] |
Transplantation by open surgery | ||
Collagen | 6 (21%) | |
Ascorbic acid-mediated sheet | 2 (7%) | |
Fibrin glue | 1 (4%) | [125] |
Cell dose | ||
Less than 10 million | 8 (26%) | |
10–20 million | 5 (16%) | |
Over 20 million | 7 (23%) | |
Unspecified | 11 (35%) | |
Follow-up | ||
Up to 6 months | 4 (13%) | |
Up to 12 months | 6 (19%) | |
Up to 2 years | 11 (35%) | |
Up to 3 years | 7 (23%) | |
Over 3 years | 2 (6%) | |
Assessments | ||
Radiology (MRI, X-ray) | 24 (77%) | |
Arthroscopic assessment incl. histology | 17 (54%) | |
IKDC | 10 (32%) | |
VAS pain | 12 (39%) | |
Tegner activity scale | 8 (26%) | |
Lysholm | 6 (19%) | |
KOOS | 5 (16%) | |
Function (no scoring systems or unspecified) | 4 (13%) | |
ICRS cartilage injury evaluation package | 3 (10%) | |
Clinical symptoms/outcomes (no scoring system or unspecified) | 3 (10%) | |
(Revised) Hospital for special surgery knee-rating scale | 2 (6%) | |
Functional Rating Index | 2 (6%) | |
WOMAC | 5 (16%) | |
AOFAS score | 2 (6%) | |
Knee Society Score | 1 (3%) | [110] |
Harris Hip Score | 1 (3%) | [112] |
Concomitant procedures | ||
Subchondral bone marrow stimulation (multiple perforation, drilling, abrasion chondroplasty) | 11 (35%) | |
Debridement, synovectomy, excision of degenerative tears (no subchondral bone marrow stimulation) | 8 (26%) | |
ACL reconstruction, meniscus repair, osteotomy, or patella alignment, ACL calcification removal, trochlear resurfacing, osteochondral fragment fixation | 8 (26%) | |
None | 6 (19%) | |
Not specified | 3 (10%) | |
Previous procedures | ||
Microfractures/multiple perforation/multiple drilling | 6 (19%) | |
Menisectomy | 6 (19%) | |
ACL reconstruction | 4 (13%) | |
Multiple (microfracture, debridement) | 1 (3%) | [119] |
ACI | 2 (6%) | |
None | 6 (19%) | |
Not specified | 9 (29%) |
Title | Cell source | Country | Clinical trial phase | Condition | Study design | Enrolment | Follow-up | Arm(s) | Cell delivery | Primary outcomes | Study status (on 8.3.2016) | ClinicalTrials.gov Identifier |
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Autologous cells | ||||||||||||
Mesenchymal Stem Cells in Knee Cartilage Injuries | Bone marrow | Jordan | II | Advanced knee articular cartilage injury | Non-randomized parallel assignment; double blind | 13 | 12 months | Culture expanded MSCs alone vs. MSC with platelet lysate | Intra-articular injection | Therapeutic benefit | Completed in August 2015; no publication found | NCT02118519 |
Adult Stem Cell Therapy for Repairing Articular Cartilage in Gonarthrosis | Bone marrow | Spain | I/II | Gonarthrosis grade 2–3 | Open label; single group assignment | 15 | 12 months | Culture expanded MSCs (40 million cells) | Articular injection | Feasibility/safety | Completed in January 2013; no publication found | NCT01227694 |
Autologous Bone Marrow Mesenchymal Stem Cells Transplantation for Articular Cartilage Defects Repair | Bone marrow | UK | I/II | Knee articular cartilage defects | Randomized parallel assignment; double blind | 10 | 12 months | MSCs (fresh or cultured unspecified) | Intra-articular injection | Change in WOMAC | Unknown (estimated study completion date; July 2014) | NCT01895413 |
Mesenchymal Stem Cell for Osteonecrosis of the Femoral Head | Bone marrow | China | 0 | Osteochondritis of the femoral head | Open label single group assignment | 15 | 5 years | Culture expanded MSC and bone marrow nuclear cells | Infusion through medial femoral circumflex artery, lateral femoral circumflex artery and obturator artery | Femoral head blood-supply artery angiographies; femoral head necrosis | Unknown (estimated study completion date; August 2015) | NCT00813267 |
The Effects of Intra-articular Injection of Mesenchymal Stem Cells in Knee Joint Osteoarthritis | Bone marrow | Iran | II | Knee joint osteoarthritis | Single centre, randomised, placebo controlled, double blind | 40 | 3 months | Culture-expanded MSCs vs. placebo | Intra-articular injection | Changes in WOMAC physical function and VAS pain | Completed in November 2012; no publication found | NCT01504464 |
Safety and Efficacy of Autologous Bone Marrow Stem Cells for Treating Osteoarthritis | Bone marrow | India | I/II | Knee OA Kellgren and Lawrence classification 3–4 | Open label single group assignment; multi-centre | 10 | 1 year | MSCs (fresh or culture-expanded unspecified) | Unknown | WOMAC pain score and safety | On-going (estimated study completion date; January 2012) | NCT01152125 |
Treatment of Knee Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells | Bone marrow | Spain | I/II | Knee OA | Randomised parallel assignment; open label | 30 | 12 months | Culture-expanded MSCs (10 million or 100 million cells) and hyaluronic acid (HyalOne®) vs. HyalOne® | Intra-articular injection | Pain and function (VAS, WOMAC, KOOS, EuroQol, SF-16, Lequesne), radiographic | On-going (estimated study completion date; February 2015) | NCT02123368 |
Intra-Articular Autologous Bone Marrow Mesenchymal Stem Cells Transplantation to Treat Mild to Moderate Osteoarthritis | Bone marrow | Malaysia | II | Mild to moderate OA based on Kellgren-Lawrence radiographic classification | Randomised parallel assignment; open label | 50 | 12 months | MSCs (fresh or culture-expanded unspecified) in hyaluronic acid “Orthovisc” vs. hyaluronic acid | Intra-articular implantation | Changes in cartilage thickness (MRI) | Unknown (estimated study completion date; March 2014) | NCT01459640 |
Treatment of Osteoarthritis by Intra-articular Injection of Bone Marrow Mesenchymal Stem Cells With Platelet Rich Plasma (CMM-PRGF/ART) | Bone marrow | Spain | I/II | Knee OA | Randomised parallel assignment; open label; multi-centre | 38 | 12 months | Culture-expanded MSCs with PRP (PRGF®) vs. PRGF® only | Intra-articular injection | Pain and function (VAS, WOMAC, KOOS, EuroQol, SF-16, Lequesne), radiographic | On-going (estimated study completion date; June 2017) | NCT02365142 |
Mesenchymal Stem Cells Enhanced With PRP Versus PRP In OA Knee (MSCPRPOAK) | Bone marrow | India | I/II | Knee OA grade 1–2 Ahlbacks radiographic staging | Randomised parallel assignment double blinded | 24 | 6 months | Culture-expanded MSCs (10 million cells) with autologous PRP vs. PRP only | Injected by lateral approach | VAS pain | Unknown (estimated study completion date; June 2014) | NCT01985633 |
Side Effects of Autologous Mesenchymal Stem Cell Transplantation in Ankle Joint Osteoarthritis | Bone marrow | Iran | I | Severe ankle OA | Single group assignment open label | 6 | 6 months | Culture-expanded MSCs | Intra-articular injection | Safety | Completed in September 2011; no publication found | NCT01436058 |
Human Autologous MSCs for the Treatment of Mid to Late Stage Knee OA | Bone marrow | Canada | I/II | Mid- to late-stage knee OA | Single group assignment, open label | 12 | 1 year | Culture-expanded MSCs (1 million, 10 million or 50 million cells) | Injection | Safety | On-going (estimated study completion date; February 2021) | NCT02351011 |
A Controlled Surveillance of the Osteoarthritic Knee Microenvironment With Regenexx® SD Treatment | Bone marrow | USA | NA | Knee OA Kellgren-Lawrence grade 2 or greater | Observational cohort study | 20 | 6 weeks | Regenexx® SD (bone marrow concentrate) | Injection | Temporal median change in protein concentration or percentage of cellular subpopulations | On-going (estimated study completion date; March 2016) | NCT02370823 |
The Effect of Platelet-rich Plasma in Patients With Osteoarthritis of the Knee | Bone marrow | Iran | III | Knee OA grade 2 and above (radiographic) | Randomised, parallel assignment, placebo controlled, double blinded | 50 | 2 year | Bone marrow aspirate vs. placebo (saline) | Intra-articular injection | VAS pain, WOMAC physical activity, cartilage repair (MRI) | Completed in April 2014; no publication found | NCT02582489 |
Outcomes Data of Bone Marrow Stem Cells to Treat Hip and Knee Osteoarthritis | Bone marrow | USA | NA | Hip and knee OA | Observational cohort study | 12 | 1 year | Bone marrow concentrate | Injection | VAS pain, Harris Hip Score or Knee Society Score, Physician Global Assessment | Completed in March 2014; no publication found | NCT01601951 |
Use of Autologous Bone Marrow Aspirate Concentrate in Painful Knee Osteoarthritis (BMAC) | Bone marrow | USA | II | Bilateral knee OA Kellgren-Lawrence grade 1–3 | Randomised, parallel assignment, placebo controlled, single blinded | 25 | 12 months | Bone marrow concentrate vs. placebo (saline) | Injection | Safety | On-going (estimated study completion date; December 2016) | NCT01931007 |
Autologous Stem Cells in Osteoarthritis | Bone marrow | Mexico | I | Knee OA Kellgren-Lawrence radiographic scale grade 2–3 | Randomised parallel assignment, open label | 61 | 6 months | Hematopoietic stem cells (fresh) vs. acetaminophen (750 mg orally TID) | Infusion | Safety | Completed in May 2014; no publication found | NCT01485198 |
The Use of Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Articular Cartilage Defects | Bone marrow | Egypt | Not given | An isolated osteochondral defect with no more than grade 1 or 2 Outerbridge | Single group assignment, open label | 25 | 12 months | Culture-expanded MSCs | Open surgery or arthroscopy | Clinical scores and radiological images | Unknown (estimated study completion date; December 2014) | NCT00891501 |
Autologous Transplantation of Mesenchymal Stem Cells (MSCs) and Scaffold in Full-thickness Articular Cartilage | Bone marrow | Iran | I | Full-thickness chondral defects | Single group assignment, open label | 6 | 12 months | Culture-expanded MSCs mixed with collagen I scaffold | Unspecified | Knee cartilage defects | Completed in December 2010; no publication found | NCT00850187 |
“One-step” Bone Marrow Mononuclear Cell Transplantation in Talar Osteochondral Lesions (BMDC) | Bone marrow | USA | III | ICRS grade 3–4 Osteochondral lesions of the talar dome | Single group assignment, open label | 140 | 24 months | Bone marrow concentrate | Arthroscopy | American Orthopaedic Foot and Ankle Society hindfoot score | On-going (estimated completion date; June 2016) | NCT02005861 |
Transplantation of Bone Marrow Stem Cells Stimulated by Proteins Scaffold to Heal Defects Articular Cartilage of the Knee | Bone marrow | France | 0 | Knee OA ICRS classification grade 4 | Single group assignment, open label | 50 | 1 year | Freshly isolated bone marrow mononuclear cells mixed with protein scaffold | Arthroscopy (one step procedure) | IKS | Unknown (estimated completion date; December 2014)) | NCT01159899 |
INSTRUCT for Repair of Knee Cartilage Defects | Bone marrow | The Netherlands | Not given | Knee articular cartilage defect | Single group assignment, open label; multi-centre | 40 | 1 year | INSTRUCT scaffold (biodegradable scaffold seeded with autologous primary chondrocytes and bone marrow cells) | Arthrotomy | Safety and lesion filling | Completed in June 2014; no publication found | NCT01041885 |
HyaloFAST Trial for Repair of Articular Cartilage in the Knee (FastTRACK) | Bone marrow | Hungary | Not given | Knee articular cartilage defect | Randomised, parallel assignment, placebo controlled, single blinded, multi-centre | 200 | 2 years | Hyalofast® scaffold with bone marrow aspirate concentrate vs. microfracture | One-step arthroscopic procedure | Changes in KOOS | On-going (estimated study completion date; June 2020) | NCT02659215 |
Autologous Adipose Stem Cells and Platelet Rich Plasma Therapy for Patients With Knee Osteoarthritis | Adipose | Vietnam | I/II | Idiopathic or secondary knee OA grade 2–3 radiographic severity | non-randomised unblinded | 16 | 12 months | Stromal vascular fraction (10–50 million cells) and platelet rich plasma (PRP) | Injection | Safety | Completed in December 2015; no publication found | NCT02142842 |
Effectiveness and Safety of Autologous ADRC for Treatment of Degenerative Damage of Knee Articular Cartilage | Adipose | Russia | I/II | Knee OA (degenerative damage of knee articular cartilage) | Single group assignment, open label | 12 | 24 weeks | Adipose-derived regenerative cells (ADRC) extracted using Celution 800/CRS System (Cytori Therapeutics, Inc.) | Intra-articular injection | Safety | On-going (estimated study completion date; December 2016) | NCT02219113 |
Autologous Adipose-Derived Stromal Cells Delivered Intra-articularly in Patients With Osteoarthritis | Adipose | USA | I/II | OA | Single group assignment, open label, multi-centre | 500 | 6 months | MSCs in PRP | Intra-articular injection | Pain score, functional rating index, visual analogue scale (VAS), physical therapy (PT) and range of motion (53), quality of life scores, reduction in analgesics, adverse events | On-going (estimated study completion date; December 2016) | NCT01739504 |
Mesenchymal Stem Cell Treatment for Primary Osteoarthritis Knee | Adipose | Taiwan | I | Bilateral primary OA Kellgren and Lawrence grade 2–3 as determined by X-ray | Single group assignment, open label, | 10 | 12 months | MSCs (8–10 million cells) | Intra-articular injections | Safety | On-going (estimated study completion date; December 2016) | NCT02544802 |
Autologous Adipose Tissue-Derived Mesenchymal Progenitor Cells Therapy for Patients With Knee Osteoarthritis | Adipose | China | II | Knee OA | Single group assignment, double blinded | 48 | 6 months | Fresh MSCs (10 million, 20 million, 50 million cells twice) vs. placebo (PBS) | Intra-articular injection | WOMAC score | Completed in December 2013; no publication found | NCT01809769 |
Clinical Trial of Autologous Adipose Tissue-Derived Mesenchymal Progenitor Cells (MPCs) Therapy for Knee Osteoarthritis | Adipose | China | II | Knee OA | Randomised, parallel assignment, placebo controlled, single blinded | 48 | 12 months | Culture-expanded MSCs vs. sodium hyaluronate | Intra-articular injection | WOMAC | On-going (estimated study completion date; July 2016) | NCT02162693 |
Outcomes Data of Adipose Stem Cells to Treat Osteoarthritis | Adipose | USA | NA | Knee OA | Observational cohort study | 50 | 12 months | Cellular concentrate | Unknown | KOOS, HOOS | On-going (estimated study completion date; September 2017) | NCT02241408 |
Clinical Trial to Evaluate Efficacy and Safety of JOINTSTEM in Patients With Degenerative Arthritis | Adipose | Korea | II/III | Knee OA | Randomised parallel assignment, double blinded | 120 | 24 weeks | MSCs (100 million cells) vs. sodium chloride | Injection | WOMAC | On-going (estimated study completion date; July 2017) | NCT02658344 |
ADIPOA–Clinical Study | Adipose | France | I | Moderate or severe knee OA | Non-randomised parallel assignment, open label | 12 | 1 year | MSCs (2 million, 10 million, 50 million cells) | Intra-articular injection | Safety | Completed in December 2014; no publication found | NCT01585857 |
Safety and Clinical Effectiveness of A3 SVF in Osteoarthritis | Adipose | USA | Not given | OA | Single group assignment, open label | 30 | 1 year | Stromal vascular fraction with activated platelet | Injection | Pain and inflammation–WOMAC scores, comprehensive inflammation blood panel | On-going (estimated study completion date; September 2015) | NCT01947348 |
Safety and Clinical Outcomes Study: SVF Deployment for Orthopaedic, Neurologic, Urologic, and Cardio-pulmonary Conditions | Adipose | USA | Not given | Neurodegenerative diseases, OA, erectile dysfunction, autoimmune diseases, cardiomyopathies or emphysema | Single group assignment, open label | 3000 | 36 months | Stromal vascular fraction | Intra-venous, intra-articular, and soft tissue injection | Safety | On-going (estimated study completion date; March 2018) | NCT01953523 |
Microfracture Versus Adipose-Derived Stem Cells for the Treatment of Articular Cartilage Defects | Adipose | USA | Not given | Knee OA | Randomised, parallel assignment, double blind | 90 | 24 months | Fibrin glue + acellular collagen dermal matrix + DSCs, + additional layer of fibrin glue vs. microfracture | Arthroscopy | KOOS | On-going (estimated study completion date; December 2020) | NCT02090140 |
Autologous Mesenchymal Stem Cells vs. Chondrocytes for the Repair of Chondral Knee Defects (ASCROD) | Adipose | Spain | I/II | Articular cartilage lesion of the femoral condyle | Randomised, parallel assignment, open label | 30 | 18 months | Cultured stem cells vs. cultured autologous chondrocytes | Unknown | Hyaline cartilage production for chondral knee lesions repair | Unknown (estimated study completion date; June 2012) | NCT01399749 |
A Phase 2 Study to Evaluate the Efficacy and Safety of JointStem in Treatment of Osteoarthritis | Adipose | USA | II | Knee OA | Randomised, parallel assignment, double blinded | 45 | 6 months | Joint stem adipose-derived (MSCs) vs. Synvisc-One (hyaluronic acid) | Cartilage volume, cartilage articular surface area, cartilage thickness, subchondral bone surface curvature (MRI) | On-going (estimated study completion date; September 2017) | NCT02674399 | |
Allogenic cells | ||||||||||||
Treatment of Knee Osteoarthritis With Allogenic Mesenchymal Stem Cells (MSV_allo) | Bone marrow | Spain | I/II | Knee OA grade 2–4 of Kellgren and Lawrence | Randomised, parallel assignment, double blinded | 30 | 1 years | Culture-expanded MSCs (40 million cells) vs. hyaluronic acid | Intra-articular transplantation | Safety | Completed in June 2014; published in August 2015 | NCT01586312 (Linked to study NCT01183728) |
Clinical Trial of Allogenic Adipose Tissue-Derived Mesenchymal Progenitor Cells Therapy for Knee Osteoarthritis | Adipose | China | I | Degenerative arthritis by radiographic criteria of Kellgren Lawrence | Randomised, parallel assignment, double blind | 18 | 48 weeks | 10 million MSCs vs. 20 million MSCs | Intra-articular injection | WOMAC | On-going (estimated study completion date; July 2017) | NCT02641860 |
Clinical Study of Umbilical Cord Tissue Mesenchymal Stem Cells (UC-MSC) for Treatment of Osteoarthritis | Umbilical Cord | Panama | I/II | Modified Kellgren-Lawrence classification grade 2–4 radiographic OA severity. | Randomised, parallel assignment, open label | 40 | 12 months | Single intra-articular injection of MSCs vs. IV injections of MSC for 3 days | Intra-articular injection; IV | Safety | On-going (estimated study completion date; March 2017) | NCT02237846 |
Safety and Feasibility Study of Mesenchymal Trophic Factor (MTF) for Treatment of Osteoarthritis | Umbilical Cord | Panama | I/II | Modified Kellgren-Lawrence classification grade 2–4 radiographic OA severity. | Non-Randomised, single group assignment, open label | 40 | 12 months | Intra-articular injection of allogeneic MTF from UC-MSC vs. 12 subcutaneous MTF injections, once per week | Intra-articular injection; subcutaneous injection | Safety | On-going (estimated study completion date; June 2017) | NCT02003131 |
A Study to Assess Safety and Efficacy of Umbilical Cord-derived Mesenchymal Stromal Cells in Knee Osteoarthritis | Umbilical Cord | Chile | I/II | Kellgren-Lawrence classification grade 1–3 radiographic OA severity | Randomised, parallel assignment, double blind | 30 | 12 months | MSCs (single dose of 20 million MSCs or double dose at 6 month interval) vs. hyaluronic acid | Intra-articular injection | Safety | On-going (estimated study completion date; December 2016) | NCT02580695 |
Human Umbilical Cord Mesenchymal Stem Cell Transplantation in Articular Cartilage Defect | Umbilical Cord | China | I | Kellgren-Lawrence classification grade 2–4 radiographic OA severity | Single group assignment, open label | 20 | 12 months | 20 million cells every month for 4 months | Intra-articular injection | Safety | On-going (estimated study completion date; December 2016) | NCT02291926 |
Evaluation of Safety and Exploratory Efficacy of CARTISTEM®, a Cell Therapy Product for Articular Cartilage Defects | Umbilical cord blood | Korea | I/II | Focal, full-thickness grade 3–4 articular cartilage defects | Single group assignment, open label | 12 | 12 months | CARTISTEM® (cultured UC MSCs mixed with sodium hyaluronate) | Unknown | Safety | On-going (estimated study completion date; May 2017) | NCT01733186 |
Study to Compare the Efficacy and Safety of Cartistem® and Microfracture in Patients With Knee Articular Cartilage Injury or Defect | Umbilical cord blood | Korea | III | Knee Articular Cartilage Injury or Defect | Randomised, parallel assignment, open label | 104 | 48 weeks | CARTISTEM® (cultured UC MSCs mixed with sodium hyaluronate) vs. Microfracture | Surgery | CRS cartilage repair assessment | Completed in January 2011; no publication found | NCT01041001 |
Follow-Up Study of CARTISTEM® vs. Microfracture for the Treatment of Knee Articular Cartilage Injury or Defect | Umbilical cord blood | Korea | III | Knee articular cartilage injury or defect | Randomised, parallel assignment, open label | 103 | 60 months | CARTISTEM® (cultured UC MSCs mixed with sodium hyaluronate) vs. microfracture | Unknown | IKDC, VAS pain, WOMAC | On-going (estimated study completion date; May 2015) | NCT01626677 |
Injections of FloGraft Therapy, Autologous Stem Cells, or Platelet Rich Plasma for the Treatment of Degenerative Joint Pain | Amniotic fluid | USA | NA | Pain associated with one of the following conditions: lumbar facet degeneration, degenerative condition causing upper extremity joint pain or degenerative condition causing lower extremity joint pain | Cohort observational study | 300 | 24 weeks | FloGraftTM (allogenic amniotic fluid-derived allograft) vs. autologous BMMSCs vs. platelet rich plasma | Injection | Pain | On-going (estimated study completion date; June 2016) | NCT01978639 |
IMPACT: Safety and Feasibility of a Single-stage Procedure for Focal Cartilage Lesions of the Knee | Unspecified | The Netherlands | I/II | Full-thickness articular cartilage lesion on the femoral condyle or trochlea | Single-group assignment, open label | 35 | 18 months | Autologous chondrons (chondrocytes with their pericellular matrix) and allogeneic MSCs in the fibrin glue carrier | Unspecified (single stage surgery) | Safety | On-going (Estimated Study Completion Date: August 2015) | NCT02037204 |
Allogeneic Mesenchymal Stem Cells in Osteoarthritis | Unspecified | India | II | Kellgren and Lawrence classification grade 2–3 radiographic OA severity | Randomised, double blind, multi-centre | 60 | 2 years | Culture-expanded MSCs in 2 ml plasmalyte + 2 ml, hyaluronan vs. 2 ml, plasmalyte + 2 ml, hyaluronan | Intra-articular | Safety and tolerability | Unknown (estimated study completion date; July 2014 | NCT01453738 |
Allogeneic Mesenchymal Stem Cells for Osteoarthritis | Unspecified | Malaysia | II | Kellgren and Lawrence classification grade 2–3 OA | Randomised, double blind, multi-centre | 72 | 1 year | Culture-expanded MSCs in 2 ml plasmalyte + 2 ml, hyaluronan vs. 2 ml, plasmalyte + 2 ml, hyaluronan | Intra-articular | Safety and tolerability | Unknown (estimated study completion date; February 2013) | NCT01448434 |
Autologous or allogenic unspecified | ||||||||||||
Transplantation of Bone Marrow Derived Mesenchymal Stem Cells in Affected Knee Osteoarthritis by Rheumatoid Arthritis | Bone marrow | II/III | Iran | Rheumatoid arthritis | Randomised, parallel assignment, open label | 60 | 6 months | MSCs vs. saline | Intra-articular injection | Pain | Completed in December 2011; no publication found | NCT01873625 |
Safety and Efficacy Study of MSB-CAR001 in Subjects 6 Weeks Post an Anterior Cruciate Ligament Reconstruction | Unknown | I/II | Australia | Anterior cruciate ligament injury | Randomised, parallel assignment, double blind | 24 | 2 year | MSB-CAR001 (a preparation of MSCs) with hyaluronan vs. hyaluronan alone | Injection | Safety | Unknown | NCT01088191 |