Skip to main content

Advertisement

SpringerLink
Log in

Effect of hyaluronic acid on paracrine signaling of osteoblasts from mesenchymal stromal cells: potential impact on bone regeneration

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objectives

This study evaluated hyaluronic acids (HA) with different molecular weights as potential matrices for tissue-engineered bone grafting and their possible influence on the paracrine mechanisms of adipose-derived mesenchymal stromal cells.

Material and methods

Murine adipose mesenchymal stromal cells (mASCs) on the fourth passage were seeded in 96-well plates, osteoinduced for 27 days and exposed for 3 days to low (HA-LW) and high/low molecular weight (HA-HLW) at previously defined concentrations. Cytokines IGF-1, VEGF, FGF-2, and BMP-2 were evaluated by quantification in the supernatant.

Results

Greater expression of growth factors was observed in groups with HA-HLW compared to HA-LW. Results indicated that differentiated cells secreted fewer cytokines, namely VEGF, FGF, and BMP-2 than undifferentiated mASCs (p < 0.05). IGF-1 showed its greatest expression in the mASC HA-LW group (p < 0.05).

Conclusions

The application of HA-HLW as cell matrix in tissue engineering did not compromise mASC paracrine effect. Also, the association of HA-HLW matrix and mASCs resulted in greater expression of osteogenic growth factors. Longer periods of cell differentiation seemed to negatively affect their capacity for local paracrine stimulation.

Clinical relevance

The use of HA-HLW as matrix for undifferentiated ASCs can be positive for bone regeneration, favoring its application as cell matrix in bone grafting procedures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Shanbhag S, Shanbhag V (2015) Clinical applications of cell-based approaches in alveolar bone augmentation: a systematic review. Clin Implant Dent Relat Res 17 Suppl 1:e17–e34

    Article  Google Scholar 

  2. Egusa H, Sonoyama W, Nishimura M, Atsuta I, Akiyama K (2012) Stem cells in dentistry--part II: clinical applications. J Prosthodont Res 56(4):229–248

    Article  Google Scholar 

  3. Shanbhag S, Stavropoulos A, Suliman S, Hervig T, Mustafa K (2017) Efficacy of humanized mesenchymal stem cell cultures for bone tissue engineering: a systematic review with a focus on platelet derivatives. Tissue Eng Part B Rev 23(6):552–569

    Article  Google Scholar 

  4. Keshtkar S, Azarpira N, Ghahremani MH (2018) Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Res Ther 9(1):63

    Article  Google Scholar 

  5. Madrigal M, Rao KS, Riordan NH (2014) A review of therapeutic effects of mesenchymal stem cell secretions and induction of secretory modification by different culture methods. J Transl Med 12:260

    Article  Google Scholar 

  6. Dimitriou R, Mataliotakis GI, Angoules AG et al (2011) Complications following autologous bone graft harvesting from the iliac crest and using the RIA: a systematic review. Injury 42 Suppl 2:S3–S15

    Article  Google Scholar 

  7. Delloye C, Cornu O, Druez V et al (2007) Bone allografts: what they can offer and what they cannot. J Bone Joint Surg (Br) 89(5):574–579

    Article  Google Scholar 

  8. Kaku M, Akiba Y, Akiyama K, Akita D, Nishimura M (2015) Cell-based bone regeneration for alveolar ridge augmentation--cell source, endogenous cell recruitment and immunomodulatory function. J Prosthodont Res 59(2):96–112

    Article  Google Scholar 

  9. Schwartz Z, Goldstein M, Raviv E, Hirsch A, Ranly DM, Boyan BD (2007) Clinical evaluation of demineralized bone allograft in a hyaluronic acid carrier for sinus lift augmentation in humans: a computed tomography and histomorphometric study. Clin Oral Implants Res 18(2):204–211

    Article  Google Scholar 

  10. Dicker KT, Gurski LA, Pradhan-Bhatt S, Witt RL, Farach-Carson MC, Jia X (2014) Hyaluronan: a simple polysaccharide with diverse biological functions. Acta Biomater 10(4):1558–1570

    Article  Google Scholar 

  11. Collins MN, Birkinshaw C (2013) Hyaluronic acid-based scaffolds for tissue engineering--a review. Carbohydr Polym 92(2):1262–1279

    Article  Google Scholar 

  12. Meirelles LS, Nardi NB (2003) Murine marrow-derived mesenchymal stem cell: isolation, in vitro expansion, and characterization. Br J Haematol 123(4):702–711

    Article  Google Scholar 

  13. Guo J, Guo S, Wang Y, Yu Y (2017) Adipose-derived stem cells and hyaluronic acid based gel compatibility, studied in vitro. Mol Med Rep 16(4):4095–4100

    Article  Google Scholar 

  14. Agolli E, Diffidenti B, Di Zitti N et al (2018) Hybrid cooperative complexes of high and low molecular weight hyaluronans (Profhilo®): review of the literature and presentation of the VisionHA project. Esperienze Dermatologiche 20(1):5–14

    Article  Google Scholar 

  15. Boeckel DG, Sesterheim P, Peres TR et al (2019) Adipogenic mesenchymal stem cells and hyaluronic acid as a cellular compound for bone tissue engineering. J Craniofac Surg 30(3):777–783

    Article  Google Scholar 

  16. Mambelli LI, Santos EJC, Frazão PJR, Chaparro MB, Kerkis A, Zoppa ALV, Kerkis I (2009) Characterization of equine adipose tissue-derived progenitor cells before and after cryopreservation. Tissue Eng Part C Methods 15(1):87–94

    Article  Google Scholar 

  17. Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, Fraser JK, Hedrick MH (2005) Multipotential differentiation of adipose tissue-derived stem cell. Keio J Med 54(3):132–141. https://doi.org/10.2302/kjm.54.132

  18. Kern S, Eichler H, Stoeve J (2006) Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 24(5):1294–1301

    Article  Google Scholar 

  19. Bobis S, Jarocha D, Majka M (2006) Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol 44(4):215–230

    PubMed  Google Scholar 

  20. Meirelles LS, Fontes AM, Covas DT et al (2009) Mechanisms involved in the therapeutic properties of mesenchymal stem cells. Cytokine Growth Factor Rev 20(5-6):419–427

    Article  Google Scholar 

  21. Phinney DG, Prockop DJ (2007) Concise review: mesenchymal stem/multipotent stromal cells: the state of transdifferentiation and modes of tissue repair--current views. Stem Cells 25(11):2896–2902

    Article  Google Scholar 

  22. Prockop DJ, Oh JY (2012) Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther 20(1):14–20

    Article  Google Scholar 

  23. Vieira S, Vial S, Reis RL, Oliveira JM (2017) Nanoparticles for bone tissue engineering. Biotechnol Prog 33(3):590–611

    Article  Google Scholar 

  24. Hughes FJ (2015) Periodontium and periodontal disease. In: Vishwakarma A, Sharpe P, Shi S (eds.) Stem cell biology and tissue engineering in dental sciences, 1st edn. Academic Press, Massachussets, pp 433–444. https://doi.org/10.1016/B978-0-12-397157-9.00038-2

  25. Misawa M, Lindhe J, Araújo MG (2016) The alveolar process following single-tooth extraction: a study of maxillary incisor and premolar sites in man. Clin Oral Implants Res 27(7):884–889

    Article  Google Scholar 

  26. Chappuis V, Araújo MG, Buser D (2017) Clinical relevance of dimensional bone and soft tissue alterations post-extraction in esthetic sites. k 73(1):73–83

    Google Scholar 

  27. David-Raoudi M, Tranchepain F, Deschrevel B (2008) Differential effects of hyaluronan and its fragments on fibroblasts: relation to wound healing. Wound Repair Regen 16(2):274–287

    Article  Google Scholar 

  28. Averbeck M, Gebhardt CA, Susanne Voigt S et al (2007) Differential regulation of hyaluronan metabolism in the epidermal and dermal compartments of human skin by UVB irradiation. J Invest Dermatol 127(3):687–697

    Article  Google Scholar 

  29. Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85(8):699–715

    Article  Google Scholar 

  30. D'Agostino A, Stellavato A, Busico T et al (2015) In vitro analysis of the effects on wound healing of high- and low-molecular weight chains of hyaluronan and their hybrid H-HA/L-HA complexes. BMC Cell Biol 16:19

    Article  Google Scholar 

  31. Stellavato A, La Noce M, Corsuto L et al (2017) Gianpaolo Papaccio, Chiara Schiraldi, Virginia Tirino. Hybrid complexes of high and low molecular weight hyaluronans highly enhance hascs differentiation: implication for facial bioremodelling. Cell Physiol Biochem 44(3):1078–1092

    Article  Google Scholar 

  32. Lu C, Saless N, Wang X (2013) The role of oxygen during fracture healing. Bone 52(1):220–229

    Article  Google Scholar 

  33. Kim J, Kim IS, Cho TH (2017) Bone regeneration using hyaluronic acid-based hydrogel with bone morphogenic protein-2 and human mesenchymal stem cells. Biomaterials 28(10):1830–1837

    Article  Google Scholar 

  34. Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res (355 Suppl):S7–S21

  35. Shoji T, Li M, Mifune Y (2010) Local transplantation of human multipotent adipose-derived stem cells accelerates fracture healing via enhanced osteogenesis and angiogenesis. Lab Investig 90(4):637–649

    Article  Google Scholar 

Download references

Funding

The present study was supported by grants from the International Team for Implantology (ITI) Foundation (No. 1155_2016), Switzerland, and by the National Council for Scientific and Technological Development (CNPq), Brazil.

Author information

Authors and Affiliations

  1. School of Health and Life Sciences, Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Carina Lantmann Cabreira, Roberta Limeira Fulginiti, Rosemary Sadami Arai Shinkai & Eduardo Rolim Teixeira

  2. Experimental Cardiology Center, Institute of Cardiology of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Patricia Sesterheim

Authors
  1. Carina Lantmann Cabreira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberta Limeira Fulginiti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Patricia Sesterheim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rosemary Sadami Arai Shinkai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eduardo Rolim Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eduardo Rolim Teixeira.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The present study protocol followed national and institutional guidelines for the care and use of animals and was approved by the Animal Research Ethics Committee of the Pontifical Catholic University of Rio Grande do Sul, Brazil (CEUA_1471005851428).

Informed consent

The present study does not require formal informed consent.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cabreira, C.L., Fulginiti, R.L., Sesterheim, P. et al. Effect of hyaluronic acid on paracrine signaling of osteoblasts from mesenchymal stromal cells: potential impact on bone regeneration. Clin Oral Invest 25, 4571–4578 (2021). https://doi.org/10.1007/s00784-020-03771-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-020-03771-x

Keywords

Search

Navigation