Details
| Original language | English |
|---|---|
| Pages (from-to) | 463-473 |
| Number of pages | 11 |
| Journal | Tissue Engineering - Part C: Methods |
| Volume | 17 |
| Issue number | 4 |
| Publication status | Published - 11 Jan 2011 |
Abstract
Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, the small number of stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one of the key limitations for the development of functional bioartificial cardiac tissue (BCT). We have addressed this problem by construction of a novel bioreactor with functional features of larger systems that enables the generation and in situ monitoring of miniaturized BCTs. BCTs were generated from rat cardiomyocytes to demonstrate advantages and usefulness of the bioreactor. Tissues showed spontaneous, synchronized contractions with cell orientation along the axis of strain. Cyclic stretch induced cardiomyocyte hypertrophy, demonstrated by a shift of myosin heavy chain expression from the alpha to beta isoform, together with elevated levels of atrial natriuretic factor. Stretch led to a moderate increase in systolic force (1.42±0.09mN vs. 0.96±0.09mN in controls), with significantly higher forces observed after β-adrenergic stimulation with noradrenalin (2.54±0.11mN). Combined mechanical and β-adrenergic stimulation had no synergistic effect. This study demonstrates for the first time that mechanical stimulation and direct real-time contraction force measurement can be combined into a single multimodal bioreactor system, including electrical stimulation of excitable tissue, perfusion of the culture chamber, and the possibility of (fluorescence) microscopic assessment during continuous cultivation. Thus, this bioreactor represents a valuable tool for monitoring tissue development and, ultimately, the optimization of stem cell-based tissue replacement strategies in regenerative medicine.
ASJC Scopus subject areas
- Chemical Engineering(all)
- Bioengineering
- Medicine(all)
- Medicine (miscellaneous)
- Engineering(all)
- Biomedical Engineering
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In: Tissue Engineering - Part C: Methods, Vol. 17, No. 4, 11.01.2011, p. 463-473.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - A novel miniaturized multimodal bioreactor for continuous in situ assessment of bioartificial cardiac tissue during stimulation and maturation
AU - Kensah, George
AU - Gruh, Ina
AU - Viering, Jörg
AU - Schumann, Henning
AU - Dahlmann, Julia
AU - Meyer, Heiko
AU - Skvorc, David
AU - Bär, Antonia
AU - Akhyari, Payam
AU - Heisterkamp, Alexander
AU - Haverich, Axel
AU - Martin, Ulrich
PY - 2011/1/11
Y1 - 2011/1/11
N2 - Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, the small number of stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one of the key limitations for the development of functional bioartificial cardiac tissue (BCT). We have addressed this problem by construction of a novel bioreactor with functional features of larger systems that enables the generation and in situ monitoring of miniaturized BCTs. BCTs were generated from rat cardiomyocytes to demonstrate advantages and usefulness of the bioreactor. Tissues showed spontaneous, synchronized contractions with cell orientation along the axis of strain. Cyclic stretch induced cardiomyocyte hypertrophy, demonstrated by a shift of myosin heavy chain expression from the alpha to beta isoform, together with elevated levels of atrial natriuretic factor. Stretch led to a moderate increase in systolic force (1.42±0.09mN vs. 0.96±0.09mN in controls), with significantly higher forces observed after β-adrenergic stimulation with noradrenalin (2.54±0.11mN). Combined mechanical and β-adrenergic stimulation had no synergistic effect. This study demonstrates for the first time that mechanical stimulation and direct real-time contraction force measurement can be combined into a single multimodal bioreactor system, including electrical stimulation of excitable tissue, perfusion of the culture chamber, and the possibility of (fluorescence) microscopic assessment during continuous cultivation. Thus, this bioreactor represents a valuable tool for monitoring tissue development and, ultimately, the optimization of stem cell-based tissue replacement strategies in regenerative medicine.
AB - Stem cell-based cardiac tissue engineering is a promising approach for regenerative therapy of the injured heart. At present, the small number of stem cell-derived cardiomyocytes that can be obtained using current culture and enrichment techniques represents one of the key limitations for the development of functional bioartificial cardiac tissue (BCT). We have addressed this problem by construction of a novel bioreactor with functional features of larger systems that enables the generation and in situ monitoring of miniaturized BCTs. BCTs were generated from rat cardiomyocytes to demonstrate advantages and usefulness of the bioreactor. Tissues showed spontaneous, synchronized contractions with cell orientation along the axis of strain. Cyclic stretch induced cardiomyocyte hypertrophy, demonstrated by a shift of myosin heavy chain expression from the alpha to beta isoform, together with elevated levels of atrial natriuretic factor. Stretch led to a moderate increase in systolic force (1.42±0.09mN vs. 0.96±0.09mN in controls), with significantly higher forces observed after β-adrenergic stimulation with noradrenalin (2.54±0.11mN). Combined mechanical and β-adrenergic stimulation had no synergistic effect. This study demonstrates for the first time that mechanical stimulation and direct real-time contraction force measurement can be combined into a single multimodal bioreactor system, including electrical stimulation of excitable tissue, perfusion of the culture chamber, and the possibility of (fluorescence) microscopic assessment during continuous cultivation. Thus, this bioreactor represents a valuable tool for monitoring tissue development and, ultimately, the optimization of stem cell-based tissue replacement strategies in regenerative medicine.
UR - http://www.scopus.com/inward/record.url?scp=79953659765&partnerID=8YFLogxK
U2 - 10.1089/ten.tec.2010.0405
DO - 10.1089/ten.tec.2010.0405
M3 - Article
C2 - 21142417
AN - SCOPUS:79953659765
VL - 17
SP - 463
EP - 473
JO - Tissue Engineering - Part C: Methods
JF - Tissue Engineering - Part C: Methods
SN - 1937-3384
IS - 4
ER -