Effects of polyacrylamide hydrogel used in the treatment of osteoarthritis on mesenchymal stem cells and human osteoblasts

Year 2022, Volume: 6 Issue: 4, 498 - 502, 01.04.2022

Aşkın Nasırcılar Muhammet Volkan Bülbül , Semiha Mervenur Kalender Celal Bozkurt , İlknur Keskin

https://doi.org/10.28982/josam.1006577

Abstract

Background/Aim: Adipose-derived mesenchymal stem cells (AD-MSCs) have gained popularity for use in treating osteoarthritis (OA) although their long-term effects remain unsatisfactory for treating the end stages of OA. However, clinically injectable polyacrylamide hydrogels (PAHGs) remain in the joint indefinitely, which could make them ideal candidates as AD-MSC carriers. Our aim was to evaluate whether combinations of PAHG and AD-MSCs have positive effects on cell viability, thereby the potential of this combination prior to clinical use in OA treatment in addition to the effects of PAHG on human osteoblasts (HOBs).
Methods: Cell lines of AD-MSCs of canine origin and HOBs were culture-expanded and seeded in 96-well plates (0.5 x 105 cells/well). The PAHG substrate at doses of 2, 6, 10, 20, or 40 µL per 200 µL of sample were added to the wells, and their effects were compared to the positive and negative control groups and among substrate doses for each cell line. The experiments were repeated three times, and cell viability was studied using tetrazolium (MTT) method.
Results: Cell viability in all dose groups was significantly greater than that of their negative control groups for both cell lines (P < 0.001). Among the different dose groups, significant dose-dependent viability increases were only observed for the HOB cell line (P < 0.001). The PAHG substrate was not lethal to AD-MSCs or HOBs up to the maximum assayed doses and had positive effects on the viability of these cell lines, including slight increases in proliferation.
Conclusion: Combination of PAHG with AD-MSCs may have positive long-term effects for OA treatment. However, further trials are needed.

Keywords

Adipose-derived mesenchymal stem cells, Cell viability, Human osteoblasts, Polyacrylamide hydrogels, Osteoarthritis

References

• 1. Kloppenburg M, Berenbaum F. Osteoarthritis year in review 2019: epidemiology and therapy. Osteoarthritis Cartilage. 2020 Mar 28;(3):242-8. doi: 10.1016/j.joca.2020.01.002. Epub 2020 Jan 13. PMID: 31945457.
• 2. Martel-Pelletier J. Pathophysiology of osteoarthritis. Osteoarthritis Cartilage. 2004;12 Suppl A:S31-3. doi: 10.1016/j.joca.2003.10.002. PMID: 14698638.
• 3. McAlindon TE, Bannuru RR, Sullivan MC, Arden NK, Berenbaum F, Bierma, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2014 Mar 22;(3):363-88. doi: 10.1016/j.joca.2014.01.003. Epub 2014 Jan 24. PMID: 24462672.
• 4. Wang AT, Feng Y, Jia HH, Zhao M, Yu H. Application of mesenchymal stem cell therapy for the treatment of osteoarthritis of the knee: A concise review. World J Stem Cells. 2019 Apr 26;11(4):222-35. doi: 10.4252/wjsc.v11.i4.222. PMID: 31110603; PMCID: PMC6503460.
• 5. Zuk PA, Zhu M, Mizuno H, Huang J, Futrell JW, Katz AJ, Benhaim P, Lorenz HP, Hedrick MH. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001 Apr 7;(2):211-28. doi: 10.1089/107632701300062859. PMID: 11304456.
• 6. Krampera M, Galipeau J, Shi Y, Tarte K, Sensebe L; MSC Committee of the International Society for Cellular Therapy (ISCT). Immunological characterization of multipotent mesenchymal stromal cells--The International Society for Cellular Therapy (ISCT) working proposal. Cytotherapy. 2013 Sep 15;(9):1054-61. doi: 10.1016/j.jcyt.2013.02.010. Epub 2013 Apr 17. PMID: 23602578.
• 7. King DJ, Noss RR. Toxicity of polyacrylamide and acrylamide monomer. Rev Environ Health. 1989 Jan-Dec 8;(1-4):3-16. doi: 10.1515/reveh-1989-1-403. PMID: 2485925.
• 8. Kavoussi H, Ebrahimi A. Delayed gel indurations as an adverse effect of polyacrylamide filler and its easy treatment. Dermatol Res Pract. 2012;2012:539153. doi: 10.1155/2012/539153. Epub 2012 Oct 9. PMID: 23093956; PMCID: PMC3474229.
• 9. Leone Roberti Maggiore U, Alessandri F, Medica M, Gabelli M, Venturini PL, Ferrero S. Periurethral injection of polyacrylamide hydrogel for the treatment of stress urinary incontinence: the impact on female sexual function. J Sex Med. 2012 Dec 9;(12):3255-63. doi: 10.1111/j.1743-6109.2012.02955.x. PMID: 23206347.
• 10. Zar V, Zagorodniy N, Martinov D. Effectiveness and safety of injectable endoprosthetics of synovial fluid by cross-linked polymer noltrex for treatment OA knee. European Journal of Musculoskeletal Diseases 2012;(1):23-32.
• 11. Lee S, Stanton AE, Tong X, Yang F. Hydrogels with enhanced protein conjugation efficiency reveal stiffness-induced YAP localization in stem cells depends on biochemical cues. Biomaterials. 2019 May;202:26-34. doi: 10.1016/j.biomaterials.2019.02.021. Epub 2019 Feb 23. PMID: 30826537; PMCID: PMC6447317.
• 12. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55-63. doi: 10.1016/0022-1759(83)90303-4. PMID: 6606682.
• 13. Tonbul M, Adas M, Bekmezci T, Kara AD. Intra-articular polyacrylamide hydrogel injections are not innocent. Case Rep Orthop. 2014;2014:150709. doi: 10.1155/2014/150709. Epub 2014 Aug 13. PMID: 25197596; PMCID: PMC4147293.
• 14. Burr D. Subchondral bone in the pathogenesis of osteoarthritis. Mechanical aspects. In: Brandt KD, Doherty M, Lohmander LS, eds. Osteoarthritis, 2nd edn. Oxford, Oxford University Press, 2003:125-132.
• 15. Westacott CI. Subchondral bone in the pathogenesis of osteoarthritis. Biological effects. In: Brandt KD, Doherty M, Lohmander LS, eds. Osteoarthritis, 2nd edn. Oxford, Oxford University Press, 2003:133-42.
• 16. Dieppe P, Cushnaghan J, Young P, Kirwan J. Prediction of the progression of joint space narrowing in osteoarthritis of the knee by bone scintigraphy. Ann Rheum Dis. 1993 Aug 5;2(8):557-63. doi: 10.1136/ard.52.8.557. PMID: 8215615; PMCID: PMC1005110.
• 17. Iijima H, Isho T, Kuroki H, Takahashi M, Aoyama T. Effectiveness of mesenchymal stem cells for treating patients with knee osteoarthritis: a meta-analysis toward the establishment of effective regenerative rehabilitation. NPJ Regen Med. 2018 Sep 17;3:15. doi: 10.1038/s41536-018-0041-8. PMID: 30245848; PMCID: PMC6141619.
• 18. Fuggle NR, Cooper C, Oreffo ROC, Price AJ, Kaux JF, Maheu E, et al. Alternative and complementary therapies in osteoarthritis and cartilage repair. Aging Clin Exp Res. 2020 Apr 3;2(4):547-60. doi: 10.1007/s40520-020-01515-1. Epub 2020 Mar 13. PMID: 32170710; PMCID: PMC7170824.
• 19. Shariatzadeh M, Song J, Wilson SL. The efficacy of different sources of mesenchymal stem cells for the treatment of knee osteoarthritis. Cell Tissue Res. 2019 Dec 3;78(3):399-410. doi: 10.1007/s00441-019-03069-9. Epub 2019 Jul 15. Erratum in: Cell Tissue Res. 2019 Aug 3; PMID: 31309317.
• 20. Christensen LH, Nielsen JB, Mouritsen L, Sørensen M, Lose G. Tissue integration of polyacrylamide hydrogel: An experimental study of periurethral, perivesical, and mammary gland tissue in the pig. Dermatol Surg. 2008;(34):S68-77. doi: 10.1111/j.1524-4725.2008.34246.x. PMID: 18547185.
• 21. Fernandes TL, Gomoll AH, Lattermann C, Hernandez AJ, Bueno DF, Amano MT. Macrophage: A Potential Target on Cartilage Regeneration. Front Immunol. 2020 Feb 11;11:111. doi: 10.3389/fimmu.2020.00111. PMID: 32117263; PMCID: PMC7026000.
• 22. Overgaard A, Bliddal H, Henriksen M. Safety of intra-articular polyacrylamide hydrogel for the treatment of knee osteoarthritis symptoms: A retrospective case series. Clin Ortho Adv Res J. COARJ-100001 Volume 2018. doi: 10.3389/fimmu.2020.00111. eCollection 2020. PMID: 32117263; PMCID: PMC7026000.
• 23. Henriksen M, Overgaard A, Hartkopp A, Bliddal H. Intra-articular 2.5% polyacrylamide hydrogel for the treatment of knee osteoarthritis: an observational proof-of-concept cohort study. Clin Exp Rheumatol. 2018 Nov-Dec;36(6):1082-5. Epub 2018 Jul 18. PMID: 30148430.