BMP-12 treatment of adult mesenchymal stem cells In Vitro augments tendon-like tissue formation and defect repair In Vivo

Jonathan Y. Lee, Zuping Zhou, Peter J. Taub, Melissa Ramcharan, Yonghui Li, Takintope Akinbiyi, Edward R. Maharam, Daniel J. Leong, Damien M. Laudier, Takuya Ruike, Phillip J. Torina, Mone Zaidi, Robert J. Majeska, Mitchell B. Schaffler, Evan L. Flatow, Hui (Herb) Sun

Research output: Contribution to journalArticle

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Abstract

We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ~80% of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering.

Original languageEnglish (US)
Article numbere17531
JournalPLoS One
Volume6
Issue number3
DOIs
StatePublished - 2011
Externally publishedYes

Fingerprint

bone morphogenetic proteins
Adult Stem Cells
Tendons
tendons
Stem cells
Mesenchymal Stromal Cells
bone marrow
stem cells
Bone
Repair
Bone Marrow
Tissue
Defects
Scaffolds
collagen
Rats
Tenascin
tissue engineering
rats
cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

BMP-12 treatment of adult mesenchymal stem cells In Vitro augments tendon-like tissue formation and defect repair In Vivo. / Lee, Jonathan Y.; Zhou, Zuping; Taub, Peter J.; Ramcharan, Melissa; Li, Yonghui; Akinbiyi, Takintope; Maharam, Edward R.; Leong, Daniel J.; Laudier, Damien M.; Ruike, Takuya; Torina, Phillip J.; Zaidi, Mone; Majeska, Robert J.; Schaffler, Mitchell B.; Flatow, Evan L.; Sun, Hui (Herb).

In: PLoS One, Vol. 6, No. 3, e17531, 2011.

Research output: Contribution to journalArticle

Lee, JY, Zhou, Z, Taub, PJ, Ramcharan, M, Li, Y, Akinbiyi, T, Maharam, ER, Leong, DJ, Laudier, DM, Ruike, T, Torina, PJ, Zaidi, M, Majeska, RJ, Schaffler, MB, Flatow, EL & Sun, HH 2011, 'BMP-12 treatment of adult mesenchymal stem cells In Vitro augments tendon-like tissue formation and defect repair In Vivo', PLoS One, vol. 6, no. 3, e17531. https://doi.org/10.1371/journal.pone.0017531
Lee, Jonathan Y. ; Zhou, Zuping ; Taub, Peter J. ; Ramcharan, Melissa ; Li, Yonghui ; Akinbiyi, Takintope ; Maharam, Edward R. ; Leong, Daniel J. ; Laudier, Damien M. ; Ruike, Takuya ; Torina, Phillip J. ; Zaidi, Mone ; Majeska, Robert J. ; Schaffler, Mitchell B. ; Flatow, Evan L. ; Sun, Hui (Herb). / BMP-12 treatment of adult mesenchymal stem cells In Vitro augments tendon-like tissue formation and defect repair In Vivo. In: PLoS One. 2011 ; Vol. 6, No. 3.
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abstract = "We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ~80{\%} of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering.",
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AU - Lee, Jonathan Y.

AU - Zhou, Zuping

AU - Taub, Peter J.

AU - Ramcharan, Melissa

AU - Li, Yonghui

AU - Akinbiyi, Takintope

AU - Maharam, Edward R.

AU - Leong, Daniel J.

AU - Laudier, Damien M.

AU - Ruike, Takuya

AU - Torina, Phillip J.

AU - Zaidi, Mone

AU - Majeska, Robert J.

AU - Schaffler, Mitchell B.

AU - Flatow, Evan L.

AU - Sun, Hui (Herb)

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AB - We characterized the differentiation of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) into tenocyte-like cells in response to bone morphogenetic protein-12 (BMP-12). BM-MSCs were prepared from Sprague-Dawley rats and cultured as monolayers. Recombinant BMP-12 treatment (10 ng/ml) of BM-MSCs for 12 hours in vitro markedly increased expression of the tenocyte lineage markers scleraxis (Scx) and tenomodulin (Tnmd) over 14 days. Treatment with BMP-12 for a further 12-hour period had no additional effect. Colony formation assays revealed that ~80% of treated cells and their progeny were Scx- and Tnmd-positive. BM-MSCs seeded in collagen scaffolds and similarly treated with a single dose of BMP-12 also expressed high levels of Scx and Tnmd, as well as type I collagen and tenascin-c. Furthermore, when the treated BM-MSC-seeded scaffolds were implanted into surgically created tendon defects in vivo, robust formation of tendon-like tissue was observed after 21 days as evidenced by increased cell number, elongation and alignment along the tensile axis, greater matrix deposition and the elevated expression of tendon markers. These results indicate that brief stimulation with BMP-12 in vitro is sufficient to induce BM-MSC differentiation into tenocytes, and that this phenotype is sustained in vivo. This strategy of pretreating BM-MSCs with BMP-12 prior to in vivo transplantation may be useful in MSC-based tendon reconstruction or tissue engineering.

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