Abstract
The differentiation process of murine embryonic stem cells into cardiomyocytes was investigated with a compliant microfluidic platform which allows for versatile cell seeding arrangements, optical observation access, long-term cell viability, and programmable uniaxial cyclic stretch. Specifically, two environmental cues were examined with this platform-culture dimensions and uniaxial cyclic stretch. First, the cardiomyogenic differentiation process, assessed by a GFP reporter driven by the α-MHC promoter, was enhanced in microfluidic devices (μFDs) compared with conventional well-plates. The addition of BMP-2 neutralizing antibody reduced the enhancement observed in the μFDs and the addition of exogenous BMP-2 augmented the cardiomyogenic differentiation in well plates. Second, 24 h of uniaxial cyclic stretch at 1 Hz and 10% strain on day 9 of differentiation was found to have a negative impact on cardiomyogenic differentiation. This microfluidic platform builds upon an existing design and extends its capability to test cellular responses to mechanical strain. It provides capabilities not found in other systems for studying differentiation, such as seeding embryoid bodies in 2D or 3D in combination with cyclic strain. This study demonstrates that the microfluidic system contributes to enhanced cardiomyogenic differentiation and may be a superior platform compared with conventional well plates. In addition to studying the effect of cyclic stretch on cardiomyogenic differentiation, this compliant platform can also be applied to investigate other biological mechanisms.
| Original language | English |
|---|---|
| Pages (from-to) | 1840-1847 |
| Number of pages | 8 |
| Journal | Annals of Biomedical Engineering |
| Volume | 39 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2011 Jun 1 |
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Keywords
- Bone morphogenetic protein 2
- Cardiogenesis
- Embryoid bodies
- Stem cell therapy
- Uniaxial cyclic stretch
ASJC Scopus subject areas
- Biomedical Engineering
Cite this
Differentiation of embryonic stem cells into cardiomyocytes in a compliant microfluidic system. / Wan, Chen Rei; Chung, Seok; Kamm, Roger D.
In: Annals of Biomedical Engineering, Vol. 39, No. 6, 01.06.2011, p. 1840-1847.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Differentiation of embryonic stem cells into cardiomyocytes in a compliant microfluidic system
AU - Wan, Chen Rei
AU - Chung, Seok
AU - Kamm, Roger D.
PY - 2011/6/1
Y1 - 2011/6/1
N2 - The differentiation process of murine embryonic stem cells into cardiomyocytes was investigated with a compliant microfluidic platform which allows for versatile cell seeding arrangements, optical observation access, long-term cell viability, and programmable uniaxial cyclic stretch. Specifically, two environmental cues were examined with this platform-culture dimensions and uniaxial cyclic stretch. First, the cardiomyogenic differentiation process, assessed by a GFP reporter driven by the α-MHC promoter, was enhanced in microfluidic devices (μFDs) compared with conventional well-plates. The addition of BMP-2 neutralizing antibody reduced the enhancement observed in the μFDs and the addition of exogenous BMP-2 augmented the cardiomyogenic differentiation in well plates. Second, 24 h of uniaxial cyclic stretch at 1 Hz and 10% strain on day 9 of differentiation was found to have a negative impact on cardiomyogenic differentiation. This microfluidic platform builds upon an existing design and extends its capability to test cellular responses to mechanical strain. It provides capabilities not found in other systems for studying differentiation, such as seeding embryoid bodies in 2D or 3D in combination with cyclic strain. This study demonstrates that the microfluidic system contributes to enhanced cardiomyogenic differentiation and may be a superior platform compared with conventional well plates. In addition to studying the effect of cyclic stretch on cardiomyogenic differentiation, this compliant platform can also be applied to investigate other biological mechanisms.
AB - The differentiation process of murine embryonic stem cells into cardiomyocytes was investigated with a compliant microfluidic platform which allows for versatile cell seeding arrangements, optical observation access, long-term cell viability, and programmable uniaxial cyclic stretch. Specifically, two environmental cues were examined with this platform-culture dimensions and uniaxial cyclic stretch. First, the cardiomyogenic differentiation process, assessed by a GFP reporter driven by the α-MHC promoter, was enhanced in microfluidic devices (μFDs) compared with conventional well-plates. The addition of BMP-2 neutralizing antibody reduced the enhancement observed in the μFDs and the addition of exogenous BMP-2 augmented the cardiomyogenic differentiation in well plates. Second, 24 h of uniaxial cyclic stretch at 1 Hz and 10% strain on day 9 of differentiation was found to have a negative impact on cardiomyogenic differentiation. This microfluidic platform builds upon an existing design and extends its capability to test cellular responses to mechanical strain. It provides capabilities not found in other systems for studying differentiation, such as seeding embryoid bodies in 2D or 3D in combination with cyclic strain. This study demonstrates that the microfluidic system contributes to enhanced cardiomyogenic differentiation and may be a superior platform compared with conventional well plates. In addition to studying the effect of cyclic stretch on cardiomyogenic differentiation, this compliant platform can also be applied to investigate other biological mechanisms.
KW - Bone morphogenetic protein 2
KW - Cardiogenesis
KW - Embryoid bodies
KW - Stem cell therapy
KW - Uniaxial cyclic stretch
UR - http://www.scopus.com/inward/record.url?scp=79958779465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958779465&partnerID=8YFLogxK
U2 - 10.1007/s10439-011-0275-8
DO - 10.1007/s10439-011-0275-8
M3 - Article
C2 - 21336802
AN - SCOPUS:79958779465
VL - 39
SP - 1840
EP - 1847
JO - Annals of Biomedical Engineering
JF - Annals of Biomedical Engineering
SN - 0090-6964
IS - 6
ER -