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Journal of Orthopaedic Surgery and Research
Published in: Journal of Orthopaedic Surgery and Research 1/2019

Open Access 01-12-2019 | Knee Osteoarthritis | Study protocol

Efficacy and safety of culture-expanded, mesenchymal stem/stromal cells for the treatment of knee osteoarthritis: a systematic review protocol

Authors: Meredith Harrison-Brown, Corey Scholes, Kholoud Hafsi, Maimuna Marenah, Jinjie Li, Fadi Hassan, Nicola Maffulli, William D. Murrell

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2019

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Abstract

Background

Osteoarthritis is a progressive multifactorial condition of the musculoskeletal system with major symptoms including pain, loss of function, damage of articular cartilage and other tissues in the affected area. Knee osteoarthritis imposes major individual and social burden, especially with the cost and complexity of surgical interventions. Mesenchymal stem/stromal cells have been indicated as a treatment for degenerative musculoskeletal conditions given their capacity to differentiate into tissues of the musculoskeletal system.

Methods

A systematic search will be conducted in Medline, Embase, Cochrane Library, Scopus and relevant trial databases of English, Japanese, Korean, German, French, Italian, Spanish and Portuguese language papers published or in press to June 2018, with no restrictions on publication year applied. References will be screened and assessed for eligibility by two independent reviewers as per PRISMA guidelines. Cohort, cross-sectional or case controlled studies will be included for the analysis. Data extraction will be conducted using a predefined template and quality of evidence assessed. Statistical summaries and meta-analyses will be performed as necessary.

Discussion

Results will be published in relevant peer-reviewed scientific journals and presented at national or international conferences by the investigators.

Trial registration

The protocol was registered on the PROSPERO international prospective register of systematic reviews prior to commencement, CRD42018091763.
Appendix
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Literature
1.
Felson DT. An update on the pathogenesis and epidemiology of osteoarthritis. Radiol Clin North Am. 2004;42:1–9 v.CrossRefPubMed
2.
Cross M, Smith E, Hoy D, Nolte S, Ackerman I, Fransen M, et al. The global burden of hip and knee osteoarthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis. 2014;73:1323–30.CrossRefPubMed
3.
4.
Anz AW, Bapat A, Murrell WD. Concepts in regenerative medicine: past, present, and future in articular cartilage treatment. J Clin Orthop Trauma. 2016;7:137–44.CrossRefPubMedPubMedCentral
5.
6.
Jorgensen C, Djouad F, Bouffi C, Mrugala D, Noël D. Multipotent mesenchymal stromal cells in articular diseases. Best Pract Res Clin Rheumatol. 2008;22:269–84.CrossRefPubMed
7.
Ruetze M, Richter W. Adipose-derived stromal cells for osteoarticular repair: trophic function versus stem cell activity. Expert Rev Mol Med. 2014;16:e9.CrossRefPubMedPubMedCentral
8.
Fellows CR, Matta C, Zakany R, Khan IM, Mobasheri A. Adipose, bone marrow and synovial joint-derived mesenchymal stem cells for cartilage repair. Front Genet. 2016;7:213.CrossRefPubMedPubMedCentral
9.
Li C-Y, Wu X-Y, Tong J-B, Yang X-X, Zhao J-L, Zheng Q-F, et al. Comparative analysis of human mesenchymal stem cells from bone marrow and adipose tissue under xeno-free conditions for cell therapy. Stem Cell Res Ther. 2015;6:55.CrossRefPubMedPubMedCentral
10.
Mohamed-Ahmed S, Fristad I, Lie SA, Suliman S, Mustafa K, Vindenes H, et al. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison. Stem Cell Res Ther. 2018;9:168.CrossRefPubMedPubMedCentral
11.
Mochizuki T, Muneta T, Sakaguchi Y, Nimura A, Yokoyama A, Koga H, et al. Higher chondrogenic potential of fibrous synovium- and adipose synovium-derived cells compared with subcutaneous fat-derived cells: distinguishing properties of mesenchymal stem cells in humans. Arthritis Rheum. 2006;54:843–53.CrossRefPubMed
12.
Yoshimura H, Muneta T, Nimura A, Yokoyama A, Koga H, Sekiya I. Comparison of rat mesenchymal stem cells derived from bone marrow, synovium, periosteum, adipose tissue, and muscle. Cell Tissue Res. 2007;327:449–62.CrossRefPubMed
13.
Reinisch A, Etchart N, Thomas D, Hofmann NA, Fruehwirth M, Sinha S, et al. Epigenetic and in vivo comparison of diverse MSC sources reveals an endochondral signature for human hematopoietic niche formation. Blood. 2015;125:249–60.CrossRefPubMedPubMedCentral
14.
ter Huurne M, Schelbergen R, Blattes R, Blom A, de Munter W, Grevers LC, et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum. 2012;64:3604–13.CrossRefPubMed
15.
Diekman BO, Wu C-L, Louer CR, Furman BD, Huebner JL, Kraus VB, et al. Intra-articular delivery of purified mesenchymal stem cells from C57BL/6 or MRL/MpJ superhealer mice prevents posttraumatic arthritis. Cell Transplant. 2013;22:1395–408.CrossRefPubMed
16.
Wakitani S, Goto T, Pineda SJ, Young RG, Mansour JM, Caplan AI, et al. Mesenchymal cell-based repair of large, full-thickness defects of articular cartilage. J Bone Joint Surg Am. 1994;76:579–92.CrossRefPubMed
17.
Horie M, Driscoll MD, Sampson HW, Sekiya I, Caroom CT, Prockop DJ, et al. Implantation of allogenic synovial stem cells promotes meniscal regeneration in a rabbit meniscal defect model. J Bone Joint Surg Am. 2012;94:701–12.CrossRefPubMedPubMedCentral
18.
Toghraie F, Razmkhah M, Gholipour MA, Faghih Z, Chenari N, Torabi Nezhad S, et al. Scaffold-free adipose-derived stem cells (ASCs) improve experimentally induced osteoarthritis in rabbits. Arch Iran Med. 2012;15:495–9.PubMed
19.
Sato M, Uchida K, Nakajima H, Miyazaki T, Guerrero AR, Watanabe S, et al. Direct transplantation of mesenchymal stem cells into the knee joints of Hartley strain guinea pigs with spontaneous osteoarthritis. Arthritis Res Ther. 2012;14:R31.CrossRefPubMedPubMedCentral
20.
Frisbie DD, Kisiday JD, Kawcak CE, Werpy NM, McIlwraith CW. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res. 2009;27:1675–80.CrossRefPubMed
21.
Murphy JM, Fink DJ, Hunziker EB, Barry FP. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum. 2003;48:3464–74.CrossRefPubMed
22.
Lee KBL, Hui JHP, Song IC, Ardany L, Lee EH. Injectable mesenchymal stem cell therapy for large cartilage defects—a porcine model. Stem Cells. 2007;25:2964–71.CrossRefPubMed
23.
Dutton AQ, Choong PF, Goh JC-H, Lee EH, Hui JHP. Enhancement of meniscal repair in the avascular zone using mesenchymal stem cells in a porcine model. J Bone Joint Surg Br. 2010;92:169–75.CrossRefPubMed
24.
Gregory MH, Capito N, Kuroki K, Stoker AM, Cook JL, Sherman SL. A review of translational animal models for knee osteoarthritis. Arthritis. 2012;2012:764621.CrossRefPubMedPubMedCentral
25.
Little CB, Zaki S. What constitutes an “animal model of osteoarthritis” – the need for consensus? Osteoarthr Cartil. 2012;20:261–7.CrossRef
26.
Kuyinu EL, Narayanan G, Nair LS, Laurencin CT. Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res. 2016;11:19.CrossRefPubMedPubMedCentral
27.
Bansal H, Comella K, Leon J, Verma P, Agrawal D, Koka P, et al. Intra-articular injection in the knee of adipose derived stromal cells (stromal vascular fraction) and platelet rich plasma for osteoarthritis. J Transl Med. 2017;15:141.CrossRefPubMedPubMedCentral
28.
Centeno CJ, Al-Sayegh H, Freeman MD, Smith J, Murrell WD, Bubnov R. A multi-center analysis of adverse events among two thousand, three hundred and seventy two adult patients undergoing adult autologous stem cell therapy for orthopaedic conditions. Int Orthop Springer. 2016;40:1755–65.CrossRef
29.
Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4:1.CrossRefPubMedPubMedCentral
30.
Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015;350:g7647.CrossRefPubMed
31.
O’Connor D, Green S, Higgins J. Defining the review question and developing criteria for including studies. Cochrane handbook for systematic reviews of interventions: Cochrane book series. Chichester, West Sussex: Wiley; 2008. p. 81–94. ISBN: 978-0-470-51845-8.
32.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.CrossRefPubMedPubMedCentral
33.
Cook JL, Kuroki K, Visco D, Pelletier J-P, Schulz L, Lafeber FPJG. The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the dog. Osteoarthr Cartil. 2010;18(Suppl 3):S66–79.CrossRef
34.
Laverty S, Girard CA, Williams JM, Hunziker EB, Pritzker KPH. The OARSI histopathology initiative–recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthr Cartil. 2010;18(Suppl 3):S53–65.CrossRef
35.
Kraus VB, Huebner JL, DeGroot J, Bendele A. The OARSI histopathology initiative–recommendations for histological assessments of osteoarthritis in the guinea pig. Osteoarthr Cartil. 2010;18(Suppl 3):S35–52.CrossRef
36.
Glasson SS, Chambers MG, Van Den Berg WB, Little CB. The OARSI histopathology initiative–recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthr Cartil. 2010;18(Suppl 3):S17–23.CrossRef
37.
McIlwraith CW, Frisbie DD, Kawcak CE, Fuller CJ, Hurtig M, Cruz A. The OARSI histopathology initiative–recommendations for histological assessments of osteoarthritis in the horse. Osteoarthr Cartil. 2010;18(Suppl 3):S93–105.CrossRef
38.
Rutgers M, van Pelt MJP, Dhert WJA, Creemers LB, Saris DBF. Evaluation of histological scoring systems for tissue-engineered, repaired and osteoarthritic cartilage. Osteoarthr Cartil. 2010;18:12–23.CrossRef
39.
Watson PJ, Carpenter TA, Hall LD, Tyler JA. Cartilage swelling and loss in a spontaneous model of osteoarthritis visualized by magnetic resonance imaging. Osteoarthr Cartil. 1996;4:197–207.CrossRef
40.
Nolte-Ernsting CC, Adam G, Bühne M, Prescher A, Günther RW. MRI of degenerative bone marrow lesions in experimental osteoarthritis of canine knee joints. Skeletal Radiol. 1996;25:413–20.CrossRefPubMed
41.
42.
Brittenberg M, Peterson L. Introduction of an articular cartilage classification. ICRS Newsl. 1998;1:5–8.
43.
Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res. 2000;(374):212–34.
44.
Smith GD, Taylor J, Almqvist KF, Erggelet C, Knutsen G, Garcia Portabella M, et al. Arthroscopic assessment of cartilage repair: a validation study of 2 scoring systems. Arthroscopy. 2005;21:1462–7.CrossRefPubMed
45.
Kohn MD, Sassoon AA, Fernando ND. Classifications in brief: Kellgren-Lawrence classification of osteoarthritis. Clin Orthop Relat Res. 2016;474:1886–93.CrossRefPubMedPubMedCentral
46.
Jaremko JL, Jeffery D, Buller M, Wichuk S, McDougall D, Lambert RG, et al. Preliminary validation of the knee inflammation MRI scoring system (KIMRISS) for grading bone marrow lesions in osteoarthritis of the knee: data from the osteoarthritis initiative. RMD Open. 2017;3:e000355.CrossRefPubMedPubMedCentral
47.
Hunter DJ, Lo GH, Gale D, Grainger AJ, Guermazi A, Conaghan PG. The reliability of a new scoring system for knee osteoarthritis MRI and the validity of bone marrow lesion assessment: BLOKS (Boston Leeds Osteoarthritis Knee Score). Ann Rheum Dis. 2008;67:206–11.CrossRefPubMed
48.
Hunter DJ, Guermazi A, Lo GH, Grainger AJ, Conaghan PG, Boudreau RM, et al. Evolution of semi-quantitative whole joint assessment of knee OA: MOAKS (MRI Osteoarthritis Knee Score). Osteoarthr Cartil. 2011;19:990–1002.CrossRef
49.
Peterfy CG, Guermazi A, Zaim S, Tirman PFJ, Miaux Y, White D, et al. Whole-organ magnetic resonance imaging score (WORMS) of the knee in osteoarthritis. Osteoarthr Cartil. 2004;12:177–90.CrossRef
50.
Mankin HJ, Dorfman H, Lippiello L, Zarins A. Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data. J Bone Joint Surg Am. 1971;53:523–37.CrossRefPubMed
51.
Pritzker KPH, Gay S, Jimenez SA, Ostergaard K, Pelletier J-P, Revell PA, et al. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthr Cartil. 2006;14:13–29.CrossRef
52.
Escobar A, Gonzalez M, Quintana JM, Vrotsou K, Bilbao A, Herrera-Espiñeira C, et al. Patient acceptable symptom state and OMERACT-OARSI set of responder criteria in joint replacement. Identification of cut-off values. Osteoarthr Cartil. 2012;20:87–92.CrossRef
53.
Pham T, van der Heijde D, Altman RD, Anderson JJ, Bellamy N, Hochberg M, et al. OMERACT-OARSI initiative: osteoarthritis research society international set of responder criteria for osteoarthritis clinical trials revisited. Osteoarthr Cartil. 2004;12:389–99.CrossRef
54.
Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988;15:1833–40.PubMed
55.
Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee injury and osteoarthritis outcome score (KOOS)—development of a self-administered outcome measure. J Orthop Sports Phys Ther. 1998;28:88–96.CrossRefPubMed
56.
Rejeski WJ, Ettinger WH Jr, Shumaker S, Heuser MD, James P, Monu J, et al. The evaluation of pain in patients with knee osteoarthritis: the knee pain scale. J Rheumatol. 1995;22:1124–9.PubMed
57.
Hooijmans CR, Rovers MM, de Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 2014;14:43.
58.
Ghogomu EAT, Maxwell LJ, Buchbinder R, Rader T, Pardo Pardo J, Johnston RV, et al. Updated method guidelines for cochrane musculoskeletal group systematic reviews and metaanalyses. J Rheumatol. 2014;41:194–205.CrossRefPubMed
59.
Sterne JAC, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919 British Medical Journal Publishing Group.CrossRefPubMedPubMedCentral
60.
Sterne J, Higgins J, Elbers R, Reeves B, Development group for ROBINS-I. Risk of bias in non-randomized studies of interventions (ROBINS-I): detailed guidance. 2016. Available from http://​www.​riskofbias.​info. Accessed 12 June 2018.
61.
Higgins JP, Sterne JA, Savović J, Page MJ, Hróbjartsson A, Boutron I, et al. A revised tool for assessing risk of bias in randomized trials. In: Chandler J, McKenzie J, Boutron I, Welch V, editors. Cochrane methods; 2016.
62.
Hooijmans CR, IntHout J, Ritskes-Hoitinga M, Rovers MM. Meta-analyses of animal studies: an introduction of a valuable instrument to further improve healthcare. ILAR J. 2014;55:418–26.CrossRefPubMedPubMedCentral
63.
Slim K, Nini E, Forestier D, Kwiatkowski F. Methodological index for non-randomized studies (MINORS): development and validation of a new instrument. ANZ J Surg. 2003;73:712–6.CrossRefPubMed
64.
Hooijmans CR, de Vries RBM, Ritskes-Hoitinga M, Rovers MM, Leeflang MM, IntHout J, et al. Facilitating healthcare decisions by assessing the certainty in the evidence from preclinical animal studies. PLoS One. 2018;13:e0187271.CrossRefPubMedPubMedCentral
65.
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8:e1000412 Public Library of Science.CrossRefPubMedPubMedCentral
Metadata
Title
Efficacy and safety of culture-expanded, mesenchymal stem/stromal cells for the treatment of knee osteoarthritis: a systematic review protocol
Authors
Meredith Harrison-Brown
Corey Scholes
Kholoud Hafsi
Maimuna Marenah
Jinjie Li
Fadi Hassan
Nicola Maffulli
William D. Murrell
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2019
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-019-1070-8

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