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Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes

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Abstract

Local release of drugs may have many advantages for tissue repair but also presents major challenges. Bioengineering approaches allow microstructures to be fabricated that contain bioactive peptides for sustained local delivery. Heart tissue damage is associated with local increases in mechano growth factor (MGF), a member of the IGF-1 family. The E domain of MGF peptide is anti-apoptotic and a stem cell homing factor. The objectives of this study were to fabricate a microrod delivery device of poly (ethylene glycol) dimethacrylate (PEGDMA) hydrogel loaded with MGF peptide and to determine the elution profile and bioactivity of MGF. The injectable microrods are 30 kPa stiffness and 15 μm widths by 100 μm lengths, chosen to match heart stiffness and myocyte size. Successful encapsulation of native MGF peptide within microrods was achieved with delivery of MGF for 2 weeks, as measured by HPLC. Migration of human mesenchymal stem cells (hMSCs) increased with MGF microrod treatment (1.72 ± 0.23, p < 0.05). Inhibition of the apoptotic pathway in neonatal rat ventricular myocytes was induced by 8 h of hypoxia (1 % O2). Protection from apoptosis by MGF microrod treatment was shown by the TUNEL assay and increased Bcl-2 expression (2 ± 0.19, p < 0.05). Microrods without MGF regulated the cytoskeleton, adhesion, and proliferation of hMSCs, and MGF had no effect on these properties. Therefore, the combination microdevice provided both the mechanical cues and 2-week MGF bioactivity to reduce apoptosis and recruit stem cells, suggesting potential use of MGF microrods for cardiac regeneration therapy in vivo.

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Abbreviations

hMSC:

Human mesenchymal stem cells

NRVM:

Neonatal rat ventricular myocytes

PEGDMA:

poly(ethylene glycol) dimethacrylate

EdU:

5-ethynyl-2′-deoxyuridine

DAPI:

4′,6-Diamidino-2-phenylindole

TUNEL:

Terminal deoxynucleotidyltransferase (TdT)-mediated dUTP nick end-labeling

qPCR:

Quantitative polymerase chain reaction

IGF-1:

Insulin-like growth factor 1

MGF:

Mechano growth factor

3D:

Three dimensions

FBS:

fetal bovine serum

TFA:

Trifluoroacetic acid

CCM:

Cell culture medium

BSA:

bovine serum albumin

ECM:

Extracellular matrix

PBS:

Phosphate buffered saline

SEM:

Scanning electron microscopy

LGM:

Low glucose media

References

  • K. Ates, S.Y. Yang, R.W. Orrell, A.C. Sinanan, P. Simons, A. Solomon, S. Beech, G. Goldspink, M.P. Lewis, FEBS Lett. 581, 2727–2732 (2007)

    Article  Google Scholar 

  • P. Ayala, J.I. Lopez, T.A. Desai, Tissue. Eng. Part. A. 16(8), 2519–2527 (2010)

    Article  Google Scholar 

  • M.F. Berry, A.J. Engler, Y.J. Woo, T.J. Pirolli, L.T. Bish, V. Jayasankar, K.J. Morine, T.I. Gardner, D.E. Discher, H.L. Sweeney, Am. J. Physiol. Heart. Circ. Physiol. 290, H2196 (2006)

    Article  Google Scholar 

  • J.K. Biehl, S. Yamanaka, T.A. Desai, Dev. Dyn. 238(8), 1964–1973 (2009)

    Article  Google Scholar 

  • S.Y. Boateng, T.J. Hartman, N. Ahluwalia, H. Vidula, T.A. Desai, B. Russell, Am. J. Physiol. Cell Physiol. 285, C171–C182 (2003)

    Article  Google Scholar 

  • M.A. Bray, S.P. Sheehy, K.K. Parker, Cell Motil. Cytoskeleton 65(8), 641–651 (2008)

    Article  Google Scholar 

  • S.J. Bryant, K.S. Anseth, J. Biomed. Mater. Res. 64A(1), 70–79 (2003)

    Article  Google Scholar 

  • V. Carpenter, K. Matthews, G. Devlin, S. Stuart, J. Jensen, J. Conaglen, F. Jeanplong, P. Goldspink, S.Y. Yang, G. Goldspink, J. Bass, C. McMahon, Heart. Lung. Circ. 17, 33–39 (2008)

    Article  Google Scholar 

  • J.M. Collins, P. Ayala, T.A. Desai, B. Russell, Small. 6(3), 355–360 (2010)

  • J.M. Collins, P.H. Goldspink, B. Russell, J. Mol. Cell. Cardiology. 49(6), 1042–1045 (2010)

  • H. Cui, Q. Yi, J. Feng, L. Yang, L. Tang, J. Mol. Endocrinol. 52(2), 111–120 (2014)

    Article  Google Scholar 

  • M.W. Curtis, B. Russell, Eur. J. Physiol. 462(1), 105–117 (2011)

    Article  Google Scholar 

  • M.W. Curtis, E. Budyn, T.A. Desai, A.M. Samarel, B. Russell, Biomech. Model. Mechanobiol. 12(1), 95–109 (2013)

    Article  Google Scholar 

  • J.A. Diramio, W.S. Kisaalita, G.F. Majetich, J.M. Shimkus, Biotechnol. Prog. 21(4), 1281–1288 (2005)

    Article  Google Scholar 

  • D.E. Discher, D.J. Mooney, P.W. Zandstra, Science 324(5935), 1673–1677 (2009)

    Article  Google Scholar 

  • J. Dluzniewska, A. Sarnowska, M. Beresewicz, I. Johnsomn, S.K. Srai, B. Ramesh, G. Goldspink, D.C. Gorecki, B. Zablocka, FASEB J. 19, 1896–1898 (2005)

    Google Scholar 

  • M.U. Donath, W. Zierhut, M.A. Gosteli-Peter, C. Hauri, E.R. Froesch, J. Zapf, Eur. J. Endocrinol. 139(1), 109–117 (1998)

    Article  Google Scholar 

  • G. Doroudian, M.W. Curtis, A. Gang, B. Russell, Biochem. Biophys. Res. Commun. 430(3), 1040–1046 (2013)

    Article  Google Scholar 

  • A.J. Engler, S. Sen, H.L. Sweeney, D.E. Discher, Cell 126, 677–689 (2006)

  • S. Fazel, M. Cimini, L. Chen, S. Li, D. Angoulvant, P. Fedak, S. Verma, R.D. Weisel, A. Keating, R.K. Li, J. Clin. Invest. 116(7), 1865–1877 (2006)

    Article  Google Scholar 

  • G. Goldspink, S.Y. Yang, Int. J. Sport. Nutr. Exerc. Metab. 11 Suppl:S21-7 (2001)

  • J. Grünenfelder, D.N. Miniati, S. Murata, V. Falk, E.G. Hoyt, M. Kown, M.L. Koransky, R.C. Robbins, Circulation 104(12 Suppl 1), I202–I206 (2001)

    Google Scholar 

  • K. Hattori, B. Heissig, K. Tashiro, T. Honjo, M. Tateno, J.H. Shieh, N.R. Hackett, M.S. Quitoriano, R.G. Crystal, S. Rafii, M.A. Moore, Blood 97(11), 3354–3360 (2001)

    Article  Google Scholar 

  • M. Hill, G. Goldspink, J. Physiol. 549, 409–418 (2003)

    Article  Google Scholar 

  • D. Hockenberry, G. Núñez, C. Milliman, R.D. Schreiber, S.J. Korsmeyer, Nature 348, 334–336 (1990)

    Article  Google Scholar 

  • P.K. Kandalla, G. Goldspink, G. Butler-Browne, V. Mouly, Mech. Ageing Dev. 132(4), 154–162 (2011)

    Article  Google Scholar 

  • S.J. Korsmeyer, Immunol. Today 13, 285–288 (1992)

    Article  Google Scholar 

  • Y. Li, Y. Wang, P. Wang, B. Zhang, W. Yan, J. Sun, J. Pan, J Biomater. Sci. Polym. Ed. 24(7), 849–864 (2013)

    Article  Google Scholar 

  • E. Mavrommatis, K.M. Shioura, T. Los, P.H. Goldspink, Mol. Cell. Biochem. 381(1–2), 69–83 (2013)

    Article  Google Scholar 

  • P. Mills, J.F. Lafreniere, B.F. Benabdallah, M. El Fahime, J.P. El Tremblay, Exp. Cell Res. 313, 527–537 (2007)

    Article  Google Scholar 

  • D. Motlagh, T.J. Hartman, T.A. Desai, B. Russell, J. Biomed. Mater. Res. 67(1), 148–157 (2003)

    Article  Google Scholar 

  • A. Musaro, C. Giacinti, G. Borsellino, G. Dobrowolny, L. Pelosi, L. Cairns, S. Ottolenghi, G. Cossu, G. Bernardi, L. Battistini, M. Molinaro, N. Rosenthal, Proc. Natl. Acad. Sci. U. S. A. 101, 1206–1210 (2004)

    Article  Google Scholar 

  • R. Nahta, L.X. Yuan, B. Zhang, R. Kobayashi, F.J. Esteva, Cancer Res. 65(23), 11118–11128 (2005)

    Article  Google Scholar 

  • J.R. Napier, M.F. Thomas, M. Sharma, S.C. Hodgkinson, J.J. Bass, J. Endocrinol. 163, 63–68 (1999)

    Article  Google Scholar 

  • J.J. Norman, T.A. Desai, Tissue Eng. 11(3–4), 378–386 (2005)

    Article  Google Scholar 

  • J.J. Norman, J.M. Collins, S. Sharma, B. Russell, T.A. Desai, Tissue Eng. Part A 14, 379–390 (2008)

    Article  Google Scholar 

  • D. Paul, S.M. Samuel, N. Maulik, Antioxid. Redox Signal. 11(8), 1841–1855 (2009)

    Article  Google Scholar 

  • A.M. Samarel, Am. J. Physiol. Heart Circ. Physiol. 289(6), H2291–H2301 (2005)

    Article  Google Scholar 

  • D.T. Scadden, Nature 441(7097), 1075–1079 (2006)

    Article  Google Scholar 

  • W. Schlegel, A. Raimann, D. Halbauer, D. Scharmer, S. Sagmeister, B. Wessner, M. Helmreich, G. Haeusler, M. Egerbacher, PLoS ONE 8(10), e76133 (2013)

    Article  Google Scholar 

  • A. Stavropoulou, A. Halapas, A. Sourla, A. Philippou, E. Papageorgiou, A. Papalois, M. Koutsilieris, Mol. Med. 15, 127–135 (2009)

    Article  Google Scholar 

  • R.M. Tucker, B.W. Parcher, E.F. Jones, T.A. Desai, AAPS PharmSciTech 13(2), 605–610 (2012)

    Article  Google Scholar 

  • J. Wu, K. Wu, F. Lin, Q. Luo, L. Yang, Y. Shi, G. Song, K.L. Sung, Biochem. Biophys. Res. Commun. 441(1), 202–207 (2013)

    Article  Google Scholar 

  • S.Y. Yang, G. Goldspink, FEBS Lett. 522, 156–160 (2002)

    Article  Google Scholar 

  • B. Zhang, Q. Luo, X. Mao, B. Xu, L. Yang, Y Ju, G. Song, Exp. Cell. Res. pii: S0014-4827(14)00013-5 (2014)

Download references

Acknowledgments

The authors acknowledge funding support from the NIH (HL 062426, HL 090523) and T32 HL 07692. The work was made possible by a grant from the California Institute for Regenerative Medicine (Grant Number TG2-01153). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CIRM or any other agency of the State of California.

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Authors and Affiliations

  1. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA

    Golnar Doroudian

  2. Department of Physiology and Division of Bioengineering, University of California at San Francisco, San Francisco, CA, USA

    James Pinney, Perla Ayala & Tejal A. Desai

  3. Department of Physiology and Biophysics, University of Illinois at Chicago, 835 S. Wolcott, Chicago, IL, 60612, USA

    Tamara Los & Brenda Russell

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  1. Golnar Doroudian
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  2. James Pinney
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  3. Perla Ayala
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  4. Tamara Los
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  5. Tejal A. Desai
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  6. Brenda Russell
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Correspondence to Brenda Russell.

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Doroudian, G., Pinney, J., Ayala, P. et al. Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices 16, 705–715 (2014). https://doi.org/10.1007/s10544-014-9875-z

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