Department of Orthopedic Surgery, Yeungnam University College of Medicine, Daegu, Korea
Copyright © 2020 Yeungnam University College of Medicine
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Author contributions
Conceptualization: GBK, OJS; Data curation: GBK; Formal analysis: GBK; Methodology: GBK; Project administration: OJS; Investigation, Resources: GBK; Supervision: OJS; Validation: GBK; Writing-original draft: GBK; Writing-review & editing: GBK, OJS.
Study | Study design (no. of cases) | Mean age (yr) | Mean F/U (mo) | Delivery method | Cell population (cells/mL) | Additional factor | Outcome | Complication |
---|---|---|---|---|---|---|---|---|
Wakitani et al. (2011) [33] | Case series (45) | 50 | 75 | Two-stage surgical implantation | 5.0×106 | Collagen sheet from porcine tendon | No serious complications such as tumor or infection | - |
Davatchi et al. (2011) [34] | Case series (4) | 57.8 | 12 | Intra-articular injection | 8.0‒9.0×106 | - | Pain, walking time, and the number of stairs to climb were improved | - |
Wong et al. (2013) [32] | Prospective RCT | 51 | 24 | Intra-articular injection | 1.46±0.29×107 | Microfx+MOWHTO | Better clinical outcomes and MRI in MSCs group | - |
(28 MSCs+HA vs. 28 HA) | ||||||||
Orozco et al. (2013) [31] | Case series (12) | 49 | 12 | Intra-articular injection | 4.0×107 | - | Improvement in pain relief and WOMAC; improvement of cartilage quality on MRI | - |
Davatchi et al. (2016) [35] | Case series (3) | 57.8 | 60 | Intra-articular injection | 8.0‒9.0×106 | - | Previous parameters gradually deteriorated, but better than baseline | - |
BM-MSCs, bone marrow-derived mesenchymal stem cells; OA, osteoarthritis; F/U, follow-up; RCT, randomized controlled trial; HA, hyaluronic acid; Microfx, microfracture; MOWHTO, medial open-wedge high tibial osteotomy; MRI, magnetic resonance image; WOMAC, the Western Ontario and McMaster Universities Osteoarthritis Index.
Study | Study design (no. of cases) | Mean age (yr) | Mean follow-up (mo) | Delivery method | Cell population (cells/mL) | Additional factor | Outcome | Complication |
---|---|---|---|---|---|---|---|---|
Jo et al. (2014) [14] | Case series (dose-dependent) (3 vs. 3 vs. 12) | 60 | 6 | Intra-articular injection | Low-dose: 1.0×107 | Diagnostic arthroscopy | Better clinical outcomes and decreased cartilage defect in high-dose group; Hyaline-like regeneration | No treatment-related AEs |
Mid-dose: 5.0×107 | Most common AEs: nasopharyngitis | |||||||
High-dose: 1.0×108 | Serious AEs: urinary stone | |||||||
Pak et al. (2013) [51] | Case series (100) | 51.2 | 26 | Intra-articular injection | NA (AD-SVF) | PRP+HA+CaCl2 | Pain (VAS) was improved | Joint swelling |
No tumor formation | ||||||||
Kim et al. (2015) [53] | Comparative matched-pair analysis (20 vs. 20) | 59.2 | 28.6 | Intra-articular injection vs. surgical implantation | 4.0×106 | Injection: PRP | Better clinical and second-look arthroscopic outcomes in surgical implantation group | NA |
Surgical implantation: fibrin glue | ||||||||
Second-look arthroscopy | ||||||||
Pers et al. (2016) [52] | Prospective (dose-dependent) (6 vs. 6 vs. 6) | 64.6 | 6 | Intra-articular injection | Low-dose: 2.0×106 | - | Improved clinical outcomes in all groups; Limited possible improvement on MRI | - |
Mid-dose: 1.0×107 | ||||||||
High-dose: 5.0×107 | ||||||||
Lee et al. (2019) [50] | Prospective RCT (12 MSCs vs. 12 saline) | 62.7 | 6 | Intra-articular injection | 1.0×108 | - | Significantly improved clinical outcomes in MSCs group; Increased defect in control group | - |
AD-MSC, adipose tissue-derived mesenchymal stem cell; OA, osteoarthritis; F/U, follow-up; AE, adverse event; NA, non-available; AD-SVF, adipose-derived stromal vascular fraction; PRP, platelet-rich plasma; HA, hyaluronic acid; VAS, visual analogue scale; MRI, magnetic resonance image; RCT, randomized controlled trial; MSCs, mesenchymal stem cells.
Variable | Percentage (%) |
---|---|
Stromal cell | 15‒30 |
Hematopoietic-lineage cell | |
Stem and progenitor cell | <0.1 |
Granulocyte | 10‒15 |
Monocyte | 5‒15 |
Lymphocyte | 10‒15 |
Endothelial cell | 10‒20 |
Pericyte | 3‒5 |
Study | Study design (no. of cases) | Mean age (yr) | Mean F/U (mo) | Delivery method | Cell population (cells/mL) | Additional factor | Outcome | Complication |
---|---|---|---|---|---|---|---|---|
Wakitani et al. (2011) [33] | Case series (45) | 50 | 75 | Two-stage surgical implantation | 5.0×106 | Collagen sheet from porcine tendon | No serious complications such as tumor or infection | - |
Davatchi et al. (2011) [34] | Case series (4) | 57.8 | 12 | Intra-articular injection | 8.0‒9.0×106 | - | Pain, walking time, and the number of stairs to climb were improved | - |
Wong et al. (2013) [32] | Prospective RCT | 51 | 24 | Intra-articular injection | 1.46±0.29×107 | Microfx+MOWHTO | Better clinical outcomes and MRI in MSCs group | - |
(28 MSCs+HA vs. 28 HA) | ||||||||
Orozco et al. (2013) [31] | Case series (12) | 49 | 12 | Intra-articular injection | 4.0×107 | - | Improvement in pain relief and WOMAC; improvement of cartilage quality on MRI | - |
Davatchi et al. (2016) [35] | Case series (3) | 57.8 | 60 | Intra-articular injection | 8.0‒9.0×106 | - | Previous parameters gradually deteriorated, but better than baseline | - |
Study | Study design (no. of cases) | Mean age (yr) | Mean follow-up (mo) | Delivery method | Cell population (cells/mL) | Additional factor | Outcome | Complication |
---|---|---|---|---|---|---|---|---|
Jo et al. (2014) [14] | Case series (dose-dependent) (3 vs. 3 vs. 12) | 60 | 6 | Intra-articular injection | Low-dose: 1.0×107 | Diagnostic arthroscopy | Better clinical outcomes and decreased cartilage defect in high-dose group; Hyaline-like regeneration | No treatment-related AEs |
Mid-dose: 5.0×107 | Most common AEs: nasopharyngitis | |||||||
High-dose: 1.0×108 | Serious AEs: urinary stone | |||||||
Pak et al. (2013) [51] | Case series (100) | 51.2 | 26 | Intra-articular injection | NA (AD-SVF) | PRP+HA+CaCl2 | Pain (VAS) was improved | Joint swelling |
No tumor formation | ||||||||
Kim et al. (2015) [53] | Comparative matched-pair analysis (20 vs. 20) | 59.2 | 28.6 | Intra-articular injection vs. surgical implantation | 4.0×106 | Injection: PRP | Better clinical and second-look arthroscopic outcomes in surgical implantation group | NA |
Surgical implantation: fibrin glue | ||||||||
Second-look arthroscopy | ||||||||
Pers et al. (2016) [52] | Prospective (dose-dependent) (6 vs. 6 vs. 6) | 64.6 | 6 | Intra-articular injection | Low-dose: 2.0×106 | - | Improved clinical outcomes in all groups; Limited possible improvement on MRI | - |
Mid-dose: 1.0×107 | ||||||||
High-dose: 5.0×107 | ||||||||
Lee et al. (2019) [50] | Prospective RCT (12 MSCs vs. 12 saline) | 62.7 | 6 | Intra-articular injection | 1.0×108 | - | Significantly improved clinical outcomes in MSCs group; Increased defect in control group | - |
Variable | Percentage (%) |
---|---|
Stromal cell | 15‒30 |
Hematopoietic-lineage cell | |
Stem and progenitor cell | <0.1 |
Granulocyte | 10‒15 |
Monocyte | 5‒15 |
Lymphocyte | 10‒15 |
Endothelial cell | 10‒20 |
Pericyte | 3‒5 |
BM-MSC | AD-MSC | S-MSC | hUCB-MSC | |
---|---|---|---|---|
Advantage | High chondrogenic and osteogenic potential | Easily accessible, reliable for isolation | Greater chondrogenic potential (same embryological origin as cartilage) | Direct delivery on defect |
Good expansion ability | Plentiful number of cells | Hypoimmunogenic | ||
Less affected by donor age | Histology: hyaline-like cartilage | |||
Disadvantage | Donor site pain | Relatively lower chondrogenic potential | Less osteogenic potential | Surgical implantation |
Limited number of cells | Donor site morbidity (hematoma, infection) | Not easy to obtain | High cost | |
More affected by donor age | Evidence still limited to preclinical studies | Not easy to obtain |
BM-MSCs, bone marrow-derived mesenchymal stem cells; OA, osteoarthritis; F/U, follow-up; RCT, randomized controlled trial; HA, hyaluronic acid; Microfx, microfracture; MOWHTO, medial open-wedge high tibial osteotomy; MRI, magnetic resonance image; WOMAC, the Western Ontario and McMaster Universities Osteoarthritis Index.
AD-MSC, adipose tissue-derived mesenchymal stem cell; OA, osteoarthritis; F/U, follow-up; AE, adverse event; NA, non-available; AD-SVF, adipose-derived stromal vascular fraction; PRP, platelet-rich plasma; HA, hyaluronic acid; VAS, visual analogue scale; MRI, magnetic resonance image; RCT, randomized controlled trial; MSCs, mesenchymal stem cells.
MSC, mesenchymal stem cell; BM, bone marrow-derived; AD, adipose-derived; S, synovium-derived; hUCB, human umbilical cord blood-derived.