Engineering vascularized skeletal muscle tissue

Shulamit Levenberg, Jeroen Rouwkema, Mara Macdonald, Evan S. Garfein, Daniel S. Kohane, Diane C. Darland, Robert Marini, Clemens van Blitterswijk, Richard C. Mulligan, Patricia A. D'Amore, Robert Langer

Research output: Contribution to journalArticleAcademicpeer-review

855 Citations (Scopus)

Abstract

One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.
Original languageUndefined
Pages (from-to)879-884
JournalNature biotechnology
Volume23
Issue number7
DOIs
Publication statusPublished - 2005

Keywords

  • IR-73333
  • METIS-230731

Cite this

Levenberg, S., Rouwkema, J., Macdonald, M., Garfein, E. S., Kohane, D. S., Darland, D. C., ... Langer, R. (2005). Engineering vascularized skeletal muscle tissue. Nature biotechnology, 23(7), 879-884. https://doi.org/10.1038/nbt1109
Levenberg, Shulamit ; Rouwkema, Jeroen ; Macdonald, Mara ; Garfein, Evan S. ; Kohane, Daniel S. ; Darland, Diane C. ; Marini, Robert ; van Blitterswijk, Clemens ; Mulligan, Richard C. ; D'Amore, Patricia A. ; Langer, Robert. / Engineering vascularized skeletal muscle tissue. In: Nature biotechnology. 2005 ; Vol. 23, No. 7. pp. 879-884.
@article{fcacc99575cd42db99723df615432663,
title = "Engineering vascularized skeletal muscle tissue",
abstract = "One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.",
keywords = "IR-73333, METIS-230731",
author = "Shulamit Levenberg and Jeroen Rouwkema and Mara Macdonald and Garfein, {Evan S.} and Kohane, {Daniel S.} and Darland, {Diane C.} and Robert Marini and {van Blitterswijk}, Clemens and Mulligan, {Richard C.} and D'Amore, {Patricia A.} and Robert Langer",
year = "2005",
doi = "10.1038/nbt1109",
language = "Undefined",
volume = "23",
pages = "879--884",
journal = "Nature biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "7",

}

Levenberg, S, Rouwkema, J, Macdonald, M, Garfein, ES, Kohane, DS, Darland, DC, Marini, R, van Blitterswijk, C, Mulligan, RC, D'Amore, PA & Langer, R 2005, 'Engineering vascularized skeletal muscle tissue' Nature biotechnology, vol. 23, no. 7, pp. 879-884. https://doi.org/10.1038/nbt1109

Engineering vascularized skeletal muscle tissue. / Levenberg, Shulamit; Rouwkema, Jeroen; Macdonald, Mara; Garfein, Evan S.; Kohane, Daniel S.; Darland, Diane C.; Marini, Robert; van Blitterswijk, Clemens; Mulligan, Richard C.; D'Amore, Patricia A.; Langer, Robert.

In: Nature biotechnology, Vol. 23, No. 7, 2005, p. 879-884.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Engineering vascularized skeletal muscle tissue

AU - Levenberg, Shulamit

AU - Rouwkema, Jeroen

AU - Macdonald, Mara

AU - Garfein, Evan S.

AU - Kohane, Daniel S.

AU - Darland, Diane C.

AU - Marini, Robert

AU - van Blitterswijk, Clemens

AU - Mulligan, Richard C.

AU - D'Amore, Patricia A.

AU - Langer, Robert

PY - 2005

Y1 - 2005

N2 - One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.

AB - One of the major obstacles in engineering thick, complex tissues such as muscle is the need to vascularize the tissue in vitro. Vascularization in vitro could maintain cell viability during tissue growth, induce structural organization and promote vascularization upon implantation. Here we describe the induction of endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multiculture system consisting of myoblasts, embryonic fibroblasts and endothelial cells coseeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro showed that addition of embryonic fibroblasts increased the levels of vascular endothelial growth factor expression in the construct and promoted formation and stabilization of the endothelial vessels. We studied the survival and vascularization of the engineered muscle implants in vivo in three different models. Prevascularization improved the vascularization, blood perfusion and survival of the muscle tissue constructs after transplantation.

KW - IR-73333

KW - METIS-230731

U2 - 10.1038/nbt1109

DO - 10.1038/nbt1109

M3 - Article

VL - 23

SP - 879

EP - 884

JO - Nature biotechnology

JF - Nature biotechnology

SN - 1087-0156

IS - 7

ER -

Levenberg S, Rouwkema J, Macdonald M, Garfein ES, Kohane DS, Darland DC et al. Engineering vascularized skeletal muscle tissue. Nature biotechnology. 2005;23(7):879-884. https://doi.org/10.1038/nbt1109