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Nanoscale vibration could promote tenogenic differentiation of umbilical cord mesenchymal stem cells

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Abstract

Regulation of mesenchymal stem cell (MSC) fate for targeted cell therapy applications has been a subject of interest, particularly for tissues such as tendons that possess a marginal regenerative capacity. Control of MSCs’ fate into the tendon-specific lineage has mainly been achieved by implementation of chemical growth factors. Mechanical stimuli or 3-dimensional (D) scaffolds have been used as an additional tool for the differentiation of MSCs into tenocytes, but oftentimes, they require a sophisticated bioreactor or a complex scaffold fabrication technique which reduces the feasibility of the proposed method to be used in practice. Here, we used nanovibration to induce the differentiation of MSCs toward the tenogenic fate solely by the use of nanovibration and without the need for growth factors or complex scaffolds. MSCs were cultured on 2D cell culture dishes that were connected to piezo ceramic arrays to apply nanovibration (30–80 nm and 1 kHz frequency) over 7 and 14 d. We observed that nanovibration resulted in significant overexpression of tendon-related markers in both gene expression and protein expression levels, while there was no significant differentiation into adipose and cartilage lineages. These findings could be of assistance in the mechanoregulation of MSCs for stem cell engineering and regenerative medicine applications.

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Data Availability

The data that support the findings of this study are within the manuscript or in the supplementary material of this article.

References

  • Baek J-H, Kim D-H, Lee J, Kim S-J, Chun K-H (2021) Galectin-1 accelerates high-fat diet-induced obesity by activation of peroxisome proliferator-activated receptor gamma (PPARγ) in mice. Cell Death Dis 12(1):1–11

    Article  Google Scholar 

  • Baksh D, Yao R, Tuan RS (2007) Comparison of proliferative and multilineage differentiation potential of human mesenchymal stem cells derived from umbilical cord and bone marrow. Stem Cells 25(6):1384–1392

    Article  CAS  PubMed  Google Scholar 

  • Best KT, Lee FK, Knapp E, Awad HA, Loiselle AE (2019) Deletion of NFKB1 enhances canonical NF-κB signaling and increases macrophage and myofibroblast content during tendon healing. Sci Rep 9(1):10926

    Article  PubMed  PubMed Central  Google Scholar 

  • Best KT, Nichols AE, Knapp E, Hammert WC, Ketonis C, Jonason JH, Loiselle AE (2020) NF-κB activation persists into the remodeling phase of tendon healing and promotes myofibroblast survival. Science signaling 13(658):eabb7209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burk J, Plenge A, Brehm W, Heller S, Pfeiffer B & Kasper C (2016). Induction of tenogenic differentiation mediated by extracellular tendon matrix and short-term cyclic stretching. Stem cells Internationa.

  • Chamberlain CS, Saether EE, Aktas E, Vanderby R (2017). Mesenchymal stem cell therapy on tendon/ligament healing. J Cytokine Biol 2(1)

  • Ciardulli MC, Marino L, Lamparelli EP, Guida M, Forsyth NR, Selleri C, Maffulli N (2020) Dose-response tendon-specific markers induction by growth differentiation factor-5 in human bone marrow and umbilical cord mesenchymal stem cells. Int J Mol Sci 21(16):5905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Costa-Almeida R, Calejo I, Gomes ME (2019) Mesenchymal stem cells empowering tendon regenerative therapies. Int J Mol Sci 20(12):3002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delakowski AJ, Posselt JD, Wagner CT (2022) Modular bioreactor design for directed tendon/ligament tissue engineering. Bioengineering 9(3):127

    Article  PubMed  PubMed Central  Google Scholar 

  • Gonçalves AI, Rodrigues MT, Gomes ME (2017) Tissue-engineered magnetic cell sheet patches for advanced strategies in tendon regeneration. Acta Biomater 63:110–122

    Article  PubMed  Google Scholar 

  • Hagen A, Lehmann H, Aurich S, Bauer N, Melzer M, Moellerberndt J, Burk J (2021) Scalable production of equine platelet lysate for multipotent mesenchymal stromal cell culture. Front Bioeng Biotechnol 8:613621

    Article  PubMed  PubMed Central  Google Scholar 

  • Hayashi N, Sato T, Yumoto M, Kokabu S, Fukushima Y, Kawata Y, Kawakami T (2019) Cyclic stretch induces decorin expression via yes-associated protein in tenocytes: a possible mechanism for hyperplasia in masticatory muscle tendon-aponeurosis hyperplasia. J Oral Maxillofac Surg, Med Pathol 31(3):175–179

    Article  Google Scholar 

  • Jevtić P, Edens LJ, Vuković LD, Levy DL (2014) Sizing and shaping the nucleus: mechanisms and significance. Curr Opin Cell Biol 28:16–27. https://doi.org/10.1016/j.ceb.2014.01.003

    Article  CAS  PubMed  Google Scholar 

  • Kuo CK, Tuan RS (2008) Mechanoactive tenogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A 14(10):1615–1627

    Article  CAS  PubMed  Google Scholar 

  • Lavagnino M, Wall ME, Little D, Banes AJ, Guilak F, Arnoczky SP (2015) Tendon mechanobiology: current knowledge and future research opportunities. J Orthop Res 33(6):813–822

    Article  PubMed  PubMed Central  Google Scholar 

  • Lee JY, Zhou Z, Taub PJ, Ramcharan M, Li Y, Akinbiyi T, Ruike T (2011) BMP-12 treatment of adult mesenchymal stem cells in vitro augments tendon-like tissue formation and defect repair in vivo. PloS one 6(3):e17531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lefebvre V, Angelozzi M, Haseeb A (2019) SOX9 in cartilage development and disease. Curr Opin Cell Biol 61:39–47

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin D, Alberton P, Caceres MD, Volkmer E, Schieker M, Docheva D (2017) Tenomodulin is essential for prevention of adipocyte accumulation and fibrovascular scar formation during early tendon healing. Cell Death Dis 8(10):e3116–e3116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maharam E, Yaport M, Villanueva NL, Akinyibi T, Laudier D, He Z, Sun HB (2015) Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation. Bone research 3(1):1–9

    Article  Google Scholar 

  • Mohanty N, Gulati BR, Kumar R, Gera S, Kumar P, Somasundaram RK, Kumar S (2014) Immunophenotypic characterization and tenogenic differentiation of mesenchymal stromal cells isolated from equine umbilical cord blood. In Vitro Cellular Dev Biol-Animal 50(6):538–548

    Article  CAS  Google Scholar 

  • Nikukar H, Childs PG, Curtis AS, Martin IW, Riehle MO, Dalby MJ, Reid S (2016) Production of nanoscale vibration for stimulation of human mesenchymal stem cells. J Biomed Nanotechnol 12(7):1478–1488

    Article  CAS  PubMed  Google Scholar 

  • Nikukar H, Reid S, Tsimbouri PM, Riehle MO, Curtis AS, Dalby MJ (2013) Osteogenesis of mesenchymal stem cells by nanoscale mechanotransduction. ACS Nano 7(3):2758–2767

    Article  CAS  PubMed  Google Scholar 

  • Nourissat G, Berenbaum F, Duprez D (2015) Tendon injury: from biology to tendon repair. Nat Rev Rheumatol 11(4):223–233

    Article  PubMed  Google Scholar 

  • Oliva R, Núñez I, Segunda MN, Peralta OA (2021) Tenogenic potential of equine fetal mesenchymal stem cells under the in vitro effect of bone morphogenetic protein-12 (BMP-12). J Equine Vet 104:103681

    Article  Google Scholar 

  • Parandakh A, Tafazzoli-Shadpour M, Ardeshirylajimi A, Khojasteh A, Khani M-M (2018) The effects of short-term uniaxial strain on the mechanical properties of mesenchymal stem cells upon TGF-β 1 stimulation. In Vitro Cellular & Developmental Biology-Animal 54:677–686

    Article  CAS  Google Scholar 

  • Park JS, Chu JS, Cheng C, Chen F, Chen D, Li S (2004) Differential effects of equiaxial and uniaxial strain on mesenchymal stem cells. Biotechnol Bioeng 88(3):359–368

    Article  CAS  PubMed  Google Scholar 

  • Qin T-W, Sun Y-L, Thoreson AR, Steinmann SP, Amadio PC, An K-N, Zhao C (2015) Effect of mechanical stimulation on bone marrow stromal cell–seeded tendon slice constructs: a potential engineered tendon patch for rotator cuff repair. Biomaterials 51:43–50

    Article  CAS  PubMed  Google Scholar 

  • Ryan CN, Zeugolis DI (2020) Engineering the tenogenic niche in vitro with microenvironmental tools. Advanced Therapeutics 3(2):1900072

    Article  Google Scholar 

  • Sakamoto M, Fukunaga T, Sasaki K, Seiryu M, Yoshizawa M, Takeshita N, Takano-Yamamoto T (2019) Vibration enhances osteoclastogenesis by inducing RANKL expression via NF-κB signaling in osteocytes. Bone 123:56–66

    Article  CAS  PubMed  Google Scholar 

  • Sato M, Kuroda S, Mansjur KQ, Khaliunaa G, Nagata K, Horiuchi S, Tanaka E (2015) Low-intensity pulsed ultrasound rescues insufficient salivary secretion in autoimmune sialadenitis. Arthritis Res Therapy 17(1):1–12

    Article  Google Scholar 

  • Shen H, Kormpakis I, Havlioglu N, Linderman SW, Sakiyama-Elbert SE, Erickson IE, Thomopoulos S (2016) The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing. Stem Cell Res Therapy 7(1):1–13

    Article  Google Scholar 

  • Siersbæk R, Nielsen R, Mandrup S (2010) PPARγ in adipocyte differentiation and metabolism–novel insights from genome-wide studies. FEBS Lett 584(15):3242–3249

    Article  PubMed  Google Scholar 

  • Sugiyama Y, Naito K, Goto K, Kojima Y, Furuhata A, Igarashi M, Kaneko K (2019) Effect of aging on the tendon structure and tendon-associated gene expression in mouse foot flexor tendon. Biomedical Reports 10(4):238–244

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tokunaga T, Shukunami C, Okamoto N, Taniwaki T, Oka K, Sakamoto H, Hiraki Y (2015) FGF-2 stimulates the growth of tenogenic progenitor cells to facilitate the generation of tenomodulin-positive tenocytes in a rat rotator cuff healing model. Am J Sports Med 43(10):2411–2422

    Article  PubMed  Google Scholar 

  • Tsimbouri PM, Childs PG, Pemberton GD, Yang J, Jayawarna V, Orapiriyakul W, Thomas D (2017) Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor. Nature Biomed Eng 1(9):758–770

    Article  CAS  Google Scholar 

  • Wang N, Tytell JD, Ingber DE (2009) Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus. Nat Rev Mol Cell Biol 10(1):75–82

    Article  CAS  PubMed  Google Scholar 

  • Xu B, Song G, Ju Y, Li X, Song Y, Watanabe S (2012) RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for mechanical stretch-induced tenogenic differentiation of human mesenchymal stem cells. J Cell Physiol 227(6):2722–2729

    Article  CAS  PubMed  Google Scholar 

  • Xu J, Wang W, Ludeman M, Cheng K, Hayami T, Lotz JC, Kapila S (2008) Chondrogenic differentiation of human mesenchymal stem cells in three-dimensional alginate gels. Tissue Eng Part A 14(5):667–680

    Article  CAS  PubMed  Google Scholar 

  • Xue Y, Kim HJ, Lee J, Liu Y, Hoffman T, Chen Y, . . . Cho HJ (2022) Co‐electrospun silk fibroin and gelatin methacryloyl sheet seeded with mesenchymal stem cells for tendon regeneration. Small 2107714

  • Yang G, Rothrauff BB, Tuan RS (2013) Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm. Birth Defects Res C Embryo Today 99(3):203–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yea J-H, Bae TS, Kim BJ, Cho YW, Jo CH (2020) Regeneration of the rotator cuff tendon-to-bone interface using umbilical cord-derived mesenchymal stem cells and gradient extracellular matrix scaffolds from adipose tissue in a rat model. Acta Biomater 114:104–116

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Lu Y, Zhang L, Liu Y, Zhou Y, Chen Y, Yu H (2015) Influence of different intensities of vibration on proliferation and differentiation of human periodontal ligament stem cells. Arch Med Sci 11(3):638–646

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the Shahid Beheshti University of Medical Sciences (grant no. 31747).

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Correspondence to Mohammad-Mehdi Khani.

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Karimi, E., Vahedi, N., Sarbandi, R.R. et al. Nanoscale vibration could promote tenogenic differentiation of umbilical cord mesenchymal stem cells. In Vitro Cell.Dev.Biol.-Animal 59, 401–409 (2023). https://doi.org/10.1007/s11626-023-00780-4

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