Broken hearts aren’t just for country songs. Millions of people die each year from cardiovascular disease and related complications. Damage to the muscles of the heart during events such as heart attacks is mostly irreversible and severely affects length and quality of life for those who survive.
Creating replacement muscle cells – or cardiomyocytes – from stem cells is an attractive therapeutic option but currently there are no standardized, reliable conditions for cardiomyocyte differentiation.
That might be about to change, as a talented team of researchers led by Kimimasa Tobit, University of Pittsburgh have been hard at work optimizing the differentiation approach for the readily available multipotent muscle derived stem cells (MDSC).
More specifically, here’s what the group did:
- Utilized 3-dimensional cell culture to mimic the in vivo environment, an important factor which is generally ignored in many differentiation protocols, to promote direct cell contact and signal exchange
- Added small molecule drugs to promote cardiogenic pathways (Wnt, and TGF-b), and a miRNA (miR-206) inhibitor to promote muscle differentiation
After all the dust settled, they found that the engineered muscle tissue:
- reacted like cardiac tissue to stimulation
- expressed important cardiac transcription factors (NKX2-5, GATA4, TBX5, MEF2C) and structural proteins (α-actinin and TNNT2 ) similar to cardiomyocytes
- displayed the ability to contract and displayed synchronised spontaneous calcium transients, important for the ability of the heart cells “to beat”
- required cell-to-cell contact for the production of functional cardiomyocyte-like cells
While some differences to native cardiomyocytes still remain, and the protocol therefore still requires some refining, the results still got us pumped, so check out the full details at: Tchao et al, Scientific Reports, 2014).