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Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain

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Adipose-Derived Stem Cells

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1773))

Abstract

It is critical that human adipose stem cell (hASC) tissue-engineering therapies possess appropriate mechanical properties in order to restore function of the load bearing tissues of the musculoskeletal system. In an effort to elucidate the hASC response to mechanical stimulation and develop mechanically robust tissue engineered constructs, recent research has utilized a variety of mechanical loading paradigms including cyclic tensile strain, cyclic hydrostatic pressure, and mechanical unloading in simulated microgravity. This chapter describes methods for applying these mechanical stimuli to hASC to direct differentiation for functional tissue engineering of the musculoskeletal system.

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References

  1. Awad HA, Wickham MQ, Leddy HA et al (2004) Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. Biomaterials 25(16):3211–3222

    Article  CAS  PubMed  Google Scholar 

  2. Butler DL, Goldstein SA, Guilak F (2000) Functional tissue engineering: the role of biomechanics. J Biomech Eng 122(6):570–575

    Article  CAS  PubMed  Google Scholar 

  3. Gimble JM, Katz AJ, Bunnell BA (2007) Adipose-derived stem cells for regenerative medicine. Circ Res 100(9):1249–1260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gimble J, Guilak F (2003) Adipose-derived adult stem cells: isolation, characterization, and differentiation potential. Cytotherapy 5(5):362–369

    Article  PubMed  Google Scholar 

  5. Mizuno H (2009) Adipose-derived stem cells for tissue repair and regeneration: ten years of research and a literature review. J Nippon Med Sch 76(2):56–66

    Article  PubMed  Google Scholar 

  6. Puetzer J, Williams J, Gillies A et al (2013) The effects of cyclic hydrostatic pressure on chondrogenesis and viability of human adipose- and bone marrow-derived mesenchymal stem cells in three-dimensional agarose constructs. Tissue Eng Part A 19(1–2):299–306

    Article  CAS  PubMed  Google Scholar 

  7. Finger AR, Sargent CY, Dulaney KO et al (2007) Differential effects on messenger ribonucleic acid expression by bone marrow-derived human mesenchymal stem cells seeded in agarose constructs due to ramped and steady applications of cyclic hydrostatic pressure. Tissue Eng 13(6):1151–1158

    Article  CAS  PubMed  Google Scholar 

  8. Bodle JC, Hanson AD, Loboa EG (2011) Adipose-derived stem cells in functional bone tissue engineering: lessons from bone mechanobiology. Tissue Eng Part B Rev 17(3):195–211

    Article  PubMed  PubMed Central  Google Scholar 

  9. Loboa EG, Beaupre GS, Carter DR (2001) Mechanobiology of initial pseudarthrosis formation with oblique fractures. J Orthop Res 19(6):1067–1072

    Article  CAS  PubMed  Google Scholar 

  10. Carter DR, Beaupre GS, Giori NJ et al (1998) Mechanobiology of skeletal regeneration. Clin Orthop Relat Res (355 Suppl):S41–S55

    Article  Google Scholar 

  11. Carter DR, Blenman PR, Beaupre GS (1988) Correlations between mechanical stress history and tissue differentiation in initial fracture healing. J Orthop Res 6(5):736–748

    Article  CAS  PubMed  Google Scholar 

  12. Loboa EG, Fang TD, Parker DW et al (2005) Mechanobiology of mandibular distraction osteogenesis: finite element analyses with a rat model. J Orthop Res 23(3):663–670

    Article  PubMed  Google Scholar 

  13. Carter DR, Orr TE, Fyhrie DP et al (1987) Influences of mechanical stress on prenatal and postnatal skeletal development. Clin Orthop Relat Res (219):237–250

    Google Scholar 

  14. Loboa EG, Fang TD, Warren SM et al (2004) Mechanobiology of mandibular distraction osteogenesis: experimental analyses with a rat model. Bone 34(2):336–343

    Article  PubMed  Google Scholar 

  15. Urist MR, Mazet R Jr, McLean FC (1954) The pathogenesis and treatment of delayed union and non-union; a survey of eighty-five ununited fractures of the shaft of the tibia and one hundred control cases with similar injuries. J Bone Joint Surg Am 36-A(5):931–980

    Article  CAS  PubMed  Google Scholar 

  16. Charoenpanich A, Wall ME, Tucker CJ et al (2014) Cyclic tensile strain enhances osteogenesis and angiogenesis in mesenchymal stem cells from osteoporotic donors. Tissue Eng Part A 20(1–2):67–78

    Article  CAS  PubMed  Google Scholar 

  17. Charoenpanich A, Wall ME, Tucker CJ et al (2011) Microarray analysis of human adipose-derived stem cells in three-dimensional collagen culture: osteogenesis inhibits bone morphogenic protein and Wnt signaling pathways, and cyclic tensile strain causes upregulation of proinflammatory cytokine regulators and angiogenic factors. Tissue Eng Part A 17(21–22):2615–2627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Hanson AD, Marvel SW, Bernacki SH et al (2009) Osteogenic effects of rest inserted and continuous cyclic tensile strain on hASC lines with disparate osteodifferentiation capabilities. Ann Biomed Eng 37(5):955–965

    Article  PubMed  Google Scholar 

  19. Wall ME, Rachlin A, Otey CA et al (2007) Human adipose-derived adult stem cells upregulate palladin during osteogenesis and in response to cyclic tensile strain. Am J Physiol Cell Physiol 293(5):C1532–C1538

    Article  CAS  PubMed  Google Scholar 

  20. Sheyn D, Pelled G, Netanely D et al (2010) The effect of simulated microgravity on human mesenchymal stem cells cultured in an osteogenic differentiation system: a bioinformatics study. Tissue Eng Part A 16(11):3403–3412

    Article  PubMed  PubMed Central  Google Scholar 

  21. Zayzafoon M, Gathings WE, McDonald JM (2004) Modeled microgravity inhibits osteogenic differentiation of human mesenchymal stem cells and increases adipogenesis. Endocrinology 145(5):2421–2432

    Article  CAS  PubMed  Google Scholar 

  22. Zhang S, Liu P, Chen L et al (2015) The effects of spheroid formation of adipose-derived stem cells in a microgravity bioreactor on stemness properties and therapeutic potential. Biomaterials 41:15–25

    Article  CAS  PubMed  Google Scholar 

  23. Kearney EM, Farrell E, Prendergast PJ et al (2010) Tensile strain as a regulator of mesenchymal stem cell osteogenesis. Ann Biomed Eng 38(5):1767–1779

    Article  CAS  PubMed  Google Scholar 

  24. Sumanasinghe RD, Bernacki SH, Loboa EG (2006) Osteogenic differentiation of human mesenchymal stem cells in collagen matrices: effect of uniaxial cyclic tensile strain on bone morphogenetic protein (BMP-2) mRNA expression. Tissue Eng 12(12):3459–3465

    Article  CAS  PubMed  Google Scholar 

  25. Smith RL, Rusk SF, Ellison BE et al (1996) In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure. J Orthop Res 14(1):53–60

    Article  CAS  PubMed  Google Scholar 

  26. Angele P, Yoo JU, Smith C et al (2003) Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res 21(3):451–457

    Article  CAS  PubMed  Google Scholar 

  27. Steward AJ, Kelly DJ, Wagner DR (2014) The role of calcium signalling in the chondrogenic response of mesenchymal stem cells to hydrostatic pressure. Eur Cell Mater 28:358–371

    Article  CAS  PubMed  Google Scholar 

  28. Steward AJ, Wagner DR, Kelly DJ (2013) The pericellular environment regulates cytoskeletal development and the differentiation of mesenchymal stem cells and determines their response to hydrostatic pressure. Eur Cell Mater 25:167–178

    Article  CAS  PubMed  Google Scholar 

  29. Steward AJ, Thorpe SD, Vinardell T et al (2012) Cell-matrix interactions regulate mesenchymal stem cell response to hydrostatic pressure. Acta Biomater 8(6):2153–2159

    Article  CAS  PubMed  Google Scholar 

  30. Miyanishi K, Trindade MC, Lindsey DP et al (2006) Dose- and time-dependent effects of cyclic hydrostatic pressure on transforming growth factor-beta3-induced chondrogenesis by adult human mesenchymal stem cells in vitro. Tissue Eng 12(8):2253–2262

    Article  CAS  PubMed  Google Scholar 

  31. Miyanishi K, Trindade MC, Lindsey DP et al (2006) Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro. Tissue Eng 12(6):1419–1428

    Article  CAS  PubMed  Google Scholar 

  32. Ogawa R, Mizuno S, Murphy GF et al (2009) The effect of hydrostatic pressure on three-dimensional chondroinduction of human adipose-derived stem cells. Tissue Eng Part A 15(10):2937–2945

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ogawa R, Md P, Orgill DP, Murphy GF et al (2014) Gene expression profile on hydrostatic pressure-driven three-dimensional cartilage induction using human adipose-derived stem cells and collagen gels. Tissue Eng Part A 21(1-2):257–266

    Article  CAS  PubMed  Google Scholar 

  34. Carroll SF, Buckley CT, Kelly DJ (2014) Cyclic hydrostatic pressure promotes a stable cartilage phenotype and enhances the functional development of cartilaginous grafts engineered using multipotent stromal cells isolated from bone marrow and infrapatellar fat pad. J Biomech 47(9):2115–2121

    Article  CAS  PubMed  Google Scholar 

  35. Meyers VE, Zayzafoon M, Gonda SR et al (2004) Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells. J Cell Biochem 93(4):697–707

    Article  CAS  PubMed  Google Scholar 

  36. Meyers VE, Zayzafoon M, Douglas JT et al (2005) RhoA and cytoskeletal disruption mediate reduced osteoblastogenesis and enhanced adipogenesis of human mesenchymal stem cells in modeled microgravity. J Bone Miner Res 20(10):1858–1866

    Article  CAS  PubMed  Google Scholar 

  37. Yu B, Yu D, Cao L et al (2011) Simulated microgravity using a rotary cell culture system promotes chondrogenesis of human adipose-derived mesenchymal stem cells via the p38 MAPK pathway. Biochem Biophys Res Commun 414(2):412–418

    Article  CAS  PubMed  Google Scholar 

  38. Mayer-Wagner S, Hammerschmid F, Redeker JI et al (2014) Simulated microgravity affects chondrogenesis and hypertrophy of human mesenchymal stem cells. Int Orthop 38(12):2615–2621

    Article  PubMed  Google Scholar 

  39. Yuge L, Kajiume T, Tahara H et al (2006) Microgravity potentiates stem cell proliferation while sustaining the capability of differentiation. Stem Cells Dev 15(6):921–929

    Article  CAS  PubMed  Google Scholar 

  40. Bodle JC, Teeter SD, Hluck BH et al (2014) Age-related effects on the potency of human adipose-derived stem cells: creation and evaluation of superlots and implications for musculoskeletal tissue engineering applications. Tissue Eng Part C Methods 20(12):972–983

    Article  PubMed  PubMed Central  Google Scholar 

  41. Puetzer JL, Petitte JN, Loboa EG (2010) Comparative review of growth factors for induction of three-dimensional in vitro chondrogenesis in human mesenchymal stem cells isolated from bone marrow and adipose tissue. Tissue Eng Part B Rev 16(4):435–444

    Article  CAS  PubMed  Google Scholar 

  42. Ulbrich C, Wehland M, Pietsch J et al (2014) The impact of simulated and real microgravity on bone cells and mesenchymal stem cells. Biomed Res Int 2014:928507

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was funded by a North Carolina Space Grant Fellowship (R.N.), NSF/CBET Grants 1133427 and 1702841 (E.L.), William R. Kenan Jr. Institute for Engineering, Technology and Science grant (E.L.), NIH CTSA grant 550KR71418 (E.L.), and NIH CTSA grant 550KR61325 (E.L.). We also thank Alison Nordberg for drawing the figures.

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Authors and Affiliations

  1. Joint Department of Biomedical Engineering, North Carolina State University and University of North Carolina Chapel Hill, Raleigh, NC, USA

    Rachel C. Nordberg & Josie C. Bodle

  2. College of Engineering, University of Missouri, W1024 Thomas & Nell Lafferre Hall, Columbia, MO, USA

    Elizabeth G. Loboa

Authors
  1. Rachel C. Nordberg
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  2. Josie C. Bodle
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  3. Elizabeth G. Loboa
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Corresponding author

Correspondence to Elizabeth G. Loboa .

Editor information

Editors and Affiliations

  1. Center for Stem Cell Research and Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA, USA

    Bruce A. Bunnell  & Jeffrey M. Gimble  & 

  2. LaCell LLC, New Orleans, LA, USA

    Jeffrey M. Gimble

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Nordberg, R.C., Bodle, J.C., Loboa, E.G. (2018). Mechanical Stimulation of Adipose-Derived Stem Cells for Functional Tissue Engineering of the Musculoskeletal System via Cyclic Hydrostatic Pressure, Simulated Microgravity, and Cyclic Tensile Strain. In: Bunnell, B.A., Gimble, J.M. (eds) Adipose-Derived Stem Cells. Methods in Molecular Biology, vol 1773. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7799-4_18

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  • DOI: https://doi.org/10.1007/978-1-4939-7799-4_18

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7797-0

  • Online ISBN: 978-1-4939-7799-4

  • eBook Packages: Springer Protocols

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