Multistage Adipose-Derived Stem Cell Myogenesis: An Experimental and Modeling Study

We’re sorry, something doesn't seem to be working properly.

Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Adipose-derived stem/stromal cells (ASCs) possess great potential as an autologous cell source for cell-based regenerative therapies. We have previously shown that mimicking the natural dynamic muscle loading patterns enhances differentiation capacity of ASCs into aligned myotubes. In particular, the application of uniaxial cyclic strain significantly increased ASC myogenesis in monolayer cultures. In this study, we demonstrate that the temporal expression of key myogenic markers Pax3/7, Desmin, MyoD and myosin heavy chain closely mimics patterns described for muscle satellite cells. Using these lineage markers, we propose that the progression from undifferentiated ASCs to myotubes can be described as transitions through discrete stages. Based on our experimental data, we developed a compartmental kinetic stage-transition model to provide a quantitative description of the differentiation of ASCs to terminally differentiated myotubes. The model describing ASCs’ myogenic differentiation in response to biophysical cues could help to obtain a deeper understanding of factors governing the biological responses and provide clues for experimental methods to increase the efficiency of ASC myogenesis for the development of improved muscle regenerative therapies.

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

References

  1. 1.

    Asakura, A., M. Komaki, and M. Rudnicki. Muscle satellite cells are multipotential stem cells that exhibit myogenic, osteogenic, and adipogenic differentiation. Differentiation 68(4–5):245–253, 2001.

    Article  Google Scholar 

  2. 2.

    Bershadsky, A. D., N. Q. Balaban, and B. Geiger. Adhesion-dependent cell mechanosensitivity. Annu. Rev. Cell Dev. Biol. 19:677–695, 2003.

    Article  Google Scholar 

  3. 3.

    Charge, S. B., and M. A. Rudnicki. Cellular and molecular regulation of muscle regeneration. Physiol. Rev. 84(1):209–238, 2004.

    Article  Google Scholar 

  4. 4.

    Choi, Y. S., L. G. Vincent, A. R. Lee, M. K. Dobke, and A. J. Engler. Mechanical derivation of functional myotubes from adipose-derived stem cells. Biomaterials 33(8):2482–2491, 2012.

    Article  Google Scholar 

  5. 5.

    Choi, Y. S., L. G. Vincent, A. R. Lee, K. C. Kretchmer, S. Chirasatitsin, M. K. Dobke, and A. J. Engler. The alignment and fusion assembly of adipose-derived stem cells on mechanically patterned matrices. Biomaterials 33(29):6943–6951, 2012.

    Article  Google Scholar 

  6. 6.

    Collinsworth, A. M., C. E. Torgan, S. N. Nagda, R. J. Rajalingam, W. E. Kraus, and G. A. Truskey. Orientation and length of mammalian skeletal myocytes in response to a unidirectional stretch. Cell Tissue Res. 302(2):243–251, 2000.

    Article  Google Scholar 

  7. 7.

    Dingli, D., A. Traulsen, and J. M. Pacheco. Compartmental architecture and dynamics of hematopoiesis. PLoS ONE 2(4):e345, 2007.

    Article  Google Scholar 

  8. 8.

    Doherty, J. T., K. C. Lenhart, M. V. Cameron, C. P. Mack, F. L. Conlon, and J. M. Taylor. Skeletal muscle differentiation and fusion are regulated by the BAR-containing Rho-GTPase-activating protein (Rho-GAP), GRAF1. J. Biol. Chem. 286(29):25903–25921, 2011.

    Article  Google Scholar 

  9. 9.

    Dubois, S. G., E. Z. Floyd, S. Zvonic, G. Kilroy, X. Wu, S. Carling, Y. D. Halvorsen, E. Ravussin, and J. M. Gimble. Isolation of human adipose-derived stem cells from biopsies and liposuction specimens. Methods Mol. Biol. 449:69–79, 2008.

    Google Scholar 

  10. 10.

    Engler, A. J., S. Sen, H. L. Sweeney, and D. E. Discher. Matrix elasticity directs stem cell lineage specification. Cell 126(4):677–689, 2006.

    Article  Google Scholar 

  11. 11.

    Ferrari, G., G. Cusella-De Angelis, M. Coletta, E. Paolucci, A. Stornaiuolo, G. Cossu, and F. Mavilio. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279(5356):1528–1530, 1998.

    Article  Google Scholar 

  12. 12.

    Galli, R., U. Borello, A. Gritti, M. G. Minasi, C. Bjornson, M. Coletta, M. Mora, M. G. De Angelis, R. Fiocco, G. Cossu, and A. L. Vescovi. Skeletal myogenic potential of human and mouse neural stem cells. Nat. Neurosci. 3(10):986–991, 2000.

    Article  Google Scholar 

  13. 13.

    Geng, J., G. Liu, F. Peng, L. Yang, J. Cao, Q. Li, F. Chen, J. Kong, R. Pang, and C. Zhang. Decorin promotes myogenic differentiation and mdx mice therapeutic effects after transplantation of rat adipose-derived stem cells. Cytotherapy 14(7):877–886, 2012.

    Article  Google Scholar 

  14. 14.

    Goh, B. C., S. Thirumala, G. Kilroy, R. V. Devireddy, and J. M. Gimble. Cryopreservation characteristics of adipose-derived stem cells: maintenance of differentiation potential and viability. J. Tissue Eng. Regen. Med. 1(4):322–324, 2007.

    Article  Google Scholar 

  15. 15.

    Gonda, K., T. Shigeura, T. Sato, D. Matsumoto, H. Suga, K. Inoue, N. Aoi, H. Kato, K. Sato, S. Murase, I. Koshima, and K. Yoshimura. Preserved proliferative capacity and multipotency of human adipose-derived stem cells after long-term cryopreservation. Plast. Reconstr. Surg. 121(2):401–410, 2008.

    Article  Google Scholar 

  16. 16.

    Hutton, D. L., E. M. Moore, J. Gimble, and W. L. Grayson. PDGF and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells. Tissue Eng. Part A. 19(17–18):2076–2086, 2013.

  17. 17.

    Karalaki, M., S. Fili, A. Philippou, and M. Koutsilieris. Muscle regeneration: cellular and molecular events. In Vivo 23(5):779–796, 2009.

    Google Scholar 

  18. 18.

    Kuang, S., K. Kuroda, F. Le Grand, and M. A. Rudnicki. Asymmetric self-renewal and commitment of satellite stem cells in muscle. Cell 129(5):999–1010, 2007.

    Article  Google Scholar 

  19. 19.

    Le Grand, F., and M. A. Rudnicki. Skeletal muscle satellite cells and adult myogenesis. Curr. Opin. Cell Biol. 19(6):628–633, 2007.

    Article  Google Scholar 

  20. 20.

    Lee, W. C., T. M. Maul, D. A. Vorp, J. P. Rubin, and K. G. Marra. Effects of uniaxial cyclic strain on adipose-derived stem cell morphology, proliferation, and differentiation. Biomech. Model. Mechanobiol. 6(4):265–273, 2007.

    Article  Google Scholar 

  21. 21.

    Li, Y., and J. Huard. Differentiation of muscle-derived cells into myofibroblasts in injured skeletal muscle. Am. J. Pathol. 161(3):895–907, 2002.

    Article  Google Scholar 

  22. 22.

    Liu, C., S. Baek, J. Kim, E. Vasko, R. Pyne, and C. Chan. Effect of static pre-stretch induced surface anisotropy on orientation of mesenchymal stem cells. Cell. Mol. Bioeng. 7(1):106–121, 2014.

    Article  Google Scholar 

  23. 23.

    Liu, G., H. Zhou, Y. Li, G. Li, L. Cui, W. Liu, and Y. Cao. Evaluation of the viability and osteogenic differentiation of cryopreserved human adipose-derived stem cells. Cryobiology 57(1):18–24, 2008.

    Article  Google Scholar 

  24. 24.

    Marciniak-Czochra, A., T. Stiehl, A. D. Ho, W. Jager, and W. Wagner. Modeling of asymmetric cell division in hematopoietic stem cells—regulation of self-renewal is essential for efficient repopulation. Stem Cells Dev. 18(3):377–385, 2009.

    Article  Google Scholar 

  25. 25.

    Maul, T. M., D. W. Chew, A. Nieponice, and D. A. Vorp. Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation. Biomech. Model. Mechanobiol. 10(6):939–953, 2011.

    Article  Google Scholar 

  26. 26.

    Meligy, F. Y., K. Shigemura, H. M. Behnsawy, M. Fujisawa, M. Kawabata, and T. Shirakawa. The efficiency of in vitro isolation and myogenic differentiation of MSCs derived from adipose connective tissue, bone marrow, and skeletal muscle tissue. In Vitro Cell Dev. Biol. Anim. 48(4):203–215, 2012.

    Article  Google Scholar 

  27. 27.

    Mizuno, H., P. A. Zuk, M. Zhu, H. P. Lorenz, P. Benhaim, and M. H. Hedrick. Myogenic differentiation by human processed lipoaspirate cells. Plast Reconstr. Surg. 109(1):199–209; discussion 210–191, 2002.

  28. 28.

    Nieponice, A., T. M. Maul, J. M. Cumer, L. Soletti, and D. A. Vorp. Mechanical stimulation induces morphological and phenotypic changes in bone marrow-derived progenitor cells within a three-dimensional fibrin matrix. J. Biomed. Mater. Res. A 81(3):523–530, 2007.

    Article  Google Scholar 

  29. 29.

    Olguin, H. C., Z. Yang, S. J. Tapscott, and B. B. Olwin. Reciprocal inhibition between Pax7 and muscle regulatory factors modulates myogenic cell fate determination. J. Cell Biol. 177(5):769–779, 2007.

    Article  Google Scholar 

  30. 30.

    Powell, C. A., B. L. Smiley, J. Mills, and H. H. Vandenburgh. Mechanical stimulation improves tissue-engineered human skeletal muscle. Am. J. Physiol. Cell Physiol. 283(5):C1557–1565, 2002.

    Article  Google Scholar 

  31. 31.

    Qian, J., H. Liu, Y. Lin, W. Chen, and H. Gao. A mechanochemical model of cell reorientation on substrates under cyclic stretch. PLoS ONE 8(6):e65864, 2013.

    Article  Google Scholar 

  32. 32.

    Quintero, A. J., V. J. Wright, F. H. Fu, and J. Huard. Stem cells for the treatment of skeletal muscle injury. Clin. Sports Med. 28(1):1–11, 2009.

    Article  Google Scholar 

  33. 33.

    Shi, X., and D. J. Garry. Muscle stem cells in development, regeneration, and disease. Genes Dev. 20(13):1692–1708, 2006.

    Article  Google Scholar 

  34. 34.

    Sicari, B. M., C. L. Dearth, and S. F. Badylak. Tissue engineering and regenerative medicine approaches to enhance the functional response to skeletal muscle injury. Anat. Rec. (Hoboken). 297(1):51–64, 2014.

    Article  Google Scholar 

  35. 35.

    Wagers, A. J., and I. M. Conboy. Cellular and molecular signatures of muscle regeneration: current concepts and controversies in adult myogenesis. Cell 122(5):659–667, 2005.

    Article  Google Scholar 

  36. 36.

    Wong, S. T., S. K. Teo, S. Park, K. H. Chiam, and E. K. Yim. Anisotropic rigidity sensing on grating topography directs human mesenchymal stem cell elongation. Biomech. Model. Mechanobiol. 13(1):27–39, 2014.

    Article  Google Scholar 

  37. 37.

    Yilgor Huri, P., C. A. Cook, D. L. Hutton, B. C. Goh, J. M. Gimble, D. J. DiGirolamo, and W. L. Grayson. Biophysical cues enhance myogenesis of human adipose derived stem/stromal cells. Biochem. Biophys. Res. Commun. 438(1):180–185, 2013.

  38. 38.

    Zandstra, P. W., D. A. Lauffenburger, and C. J. Eaves. A ligand-receptor signaling threshold model of stem cell differentiation control: a biologically conserved mechanism applicable to hematopoiesis. Blood 96(4):1215–1222, 2000.

    Google Scholar 

  39. 39.

    Zuk, P. A., M. Zhu, H. Mizuno, J. Huang, J. W. Futrell, A. J. Katz, P. Benhaim, H. P. Lorenz, and M. H. Hedrick. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 7(2):211–228, 2001.

    Article  Google Scholar 

Download references

Acknowledgments

We would like to thank Dr. Jeffrey Gimble for providing the ASCs and Dr. Douglas DiGirolamo for use of the Flexcell system. We also thank Sue Kulason for the computational work at early stages of the project. This work was supported by Maryland Stem Cell Research Fund (2012-MSCRFF-165) and Johns Hopkins Department of Biomedical Engineering.

Conflict of Interest

Pinar Yilgor Huri, Andrew Wang, Alexander Spector, and Warren Grayson declare that they have no conflicts of interest.

Ethical Standards

Human ASCs were isolated in accordance with an Institutional Review Board approved protocol at the Stem Cell Biology Laboratory, Pennington Biomedical Research Center. No animal studies were carried out by the authors for this study.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Warren L. Grayson.

Additional information

Associate Editor Michael R. King oversaw the review of this article.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Huri, P.Y., Wang, A., Spector, A.A. et al. Multistage Adipose-Derived Stem Cell Myogenesis: An Experimental and Modeling Study. Cel. Mol. Bioeng. 7, 497–509 (2014). https://doi.org/10.1007/s12195-014-0362-7

Download citation

Keywords

  • Adipose-derived stem cell
  • Myogenesis
  • Dynamic culture
  • Uniaxial strain
  • Kinetic stage-transition model