Evaluating the combined effect of insulin like growth factor-1, transforming growth factor-ß and fibroblast growth factor on cardiac progenitor stem cells: Implications in regenerative therapeutics of acute myocardial infarction

posted Jan 26, 2017, 1:30 AM by sourav ghosh   [ updated Jan 26, 2017, 5:32 AM ]
Gururao Hariprasad
1 Department of Biophysics, 2 Department of Stem cell facility, 3 Department of Cardio Thoracic Vascular Surgery, 4 Department ofPharmacology, 5 Department ofNuclear Magnetic Resonance, 6 Department ofPathology, All India Institute of Medical Science, New Delhi, India.

Background of the Study: Cardiac stem cells trigger paracrine mechanisms mediated by cytokines that repair infracted tissue and certain cytokines in turn bestow stem cells with effective regenerative functions. We have sought to study the effect of growth factor cocktail on cardiac progenitor stem cells, and the translational value of administering growth factors along side cardiac stem cells in animal myocardial infarction models. 
Methods and Results: Cardiac stem cells were isolated from the hearts of twelve laboratory-bred female Wistar albino rats. Stem cell progeny was confirmed by flowcytometry studies and cardiac progeny was established by Immuno-electro fluorescence studies using troponin antibody. Cultured stem cells grown in the presence and absence of growth factor cocktail was compared by inverted phase contrast microscopy for cellular morphology, MTT assay for proliferative functions and, DIGE coupled with mass spectrometric experiments to delineate possible cellular pathways. Animal experiments included injecting saline, growth factors, stem cells, and combination of stem cell and growth factor cocktail in four groups of myocardial infarction rat models. Myocardial infarction was established by magnetic resonance imaging, and post-intervention follow up studies was done for four weeks by two-dimensional M-mode echocardiography. Cells grown with growth factors were seen to have distinct cardiac morphology showing elongated cells with branching fibers and centrally placed nucleus; functionally these showed 30% increase viability, and had over expression of proteins which are known to confer cardiac protection and counter oxidative stress. Rats that received combination therapy showed significant improvement in fractional shortening, stroke volume, ejection fraction and left ventricular internal dimension as compared to rats that received individual therapy of either saline, stem cells or growth factors alone. 
Conclusions: Insulin like growth factor-1, transforming growth factor-ß and fibroblast growth factors confer distinct advantages are in terms of growth, differentiation, proliferation and cell cycle signaling. These benefits have a clear translational value in regenerative therapeutics of myocardial infarction.