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Generation of Aligned Functional Myocardial Tissue Through Microcontact Printing
Published on: March 19, 2013
Co-culture induces alignment in engineered cardiac constructs via MMP-2 expression
Jason W Nichol1, George C Engelmayr, Mingyu Cheng
1Harvard-MIT Division of Health Sciences & Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E25-330, Cambridge, MA 02139, USA.
Biochemical and Biophysical Research Communications
|June 19, 2008
Summary
Co-culturing cardiomyocytes and cardiac fibroblasts in engineered heart tissue enhances cell alignment and viability. This improvement is mediated by matrix metalloproteinase-2 (MMP-2) activity, crucial for recreating native myocardial structures.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Regenerative Medicine
Background:
- Cardiac tissue engineering faces challenges in replicating native myocardial structural complexity.
- Achieving functional engineered cardiac constructs requires precise control over cellular organization and viability.
Purpose of the Study:
- To investigate the role of physiologic ratios of cardiomyocytes (CM) and cardiac fibroblasts (CF) in enhancing cell elongation and alignment in 3D engineered cardiac constructs.
- To elucidate the underlying matrix metalloproteinase (MMP)-dependent mechanisms driving these improvements.
Main Methods:
- Engineered cardiac constructs were created using co-cultures of CM and CF at physiologic ratios, compared to CM-enriched constructs.
- Constructs were cultured in basal media or media with a general MMP inhibitor for 8 days.
- Cell alignment, MMP expression (MMP-2, MMP-9), and apoptosis were analyzed.
Main Results:
- Co-cultured constructs showed significantly increased cell alignment, which was abolished by MMP inhibition.
- Active MMP-2 protein expression was substantial in co-cultured constructs, unlike CM-enriched ones.
- Co-culture decreased apoptosis, an effect independent of MMP inhibition, while altering pro-MMP-2 and pro-MMP-9 expression.
Conclusions:
- Co-culture of CF with CM in engineered cardiac constructs promotes cell elongation and alignment through enhanced MMP-2 activity.
- Physiologic ratios of CM and CF improve engineered cardiac construct viability independently of MMP activity.
- These findings offer a strategy for developing more biomimetic engineered cardiac tissues.
