Cardiac differentiation potential of human induced pluripotent stem cells in a 3D self-assembling peptide scaffold.

In the past decade, various strategies for cardiac reparative medicine involving stem cells from multiple sources have been investigated. However, the intra-cardiac implantation of cells with contractile ability may seriously disrupt the cardiac syncytium and de-synchronize cardiac rhythm. For this reason, bioactive cardiac implants, consisting of stem cells embedded in biomaterials that act like band aids, have been exploited to repair the cardiac wall after myocardial infarction. For such bioactive implants to function properly after transplantation, the choice of biomaterial is equally important as the selection of the stem cell source. While adult stem cells have shown promising results, they have various disadvantages including low proliferative potential in vitro, which make their successful usage in human transplants difficult. As a first step towards the development of a bioactive cardiac patch, we investigate here the cardiac differentiation properties of human induced pluripotent stem cells (hiPSCs) when cultured with and without ascorbic acid (AA) and when embedded in RAD16-I, a biomaterial commonly used to develop cardiac implants. In adherent cultures and in the absence of RAD16-I, AA promotes the cardiac differentiation of hiPSCs by enhancing the expression of specific cardiac genes and proteins and by increasing the number of contracting clusters. In turn, embedding in peptide hydrogel based on RAD16-I interferes with the normal cardiac differentiation progression. Embedded hiPSCs up-regulate genes associated with early cardiogenesis by up to 105 times independently of the presence of AA. However, neither connexin 43 nor troponin I proteins, which are related with mature cardiomyocytes, were detected and no contraction was noted in the constructs. Future experiments will need to focus on characterizing the mature cardiac phenotype of these cells when implanted into infarcted myocardia and assess their regenerative potential in vivo.

Self-assembling peptide scaffolds as innovative platforms for drug and cell delivery systems in cardiac regeneration.

Today, the use of biomaterials in many biomedical platforms is becoming increasingly popular due to their high diversity, infinite mimicking capacity, and emerging functions. Applications currently cover diverse areas in biomedicine including systems for cell isolation, expansion and maintenance, platforms for drug and cell delivery, scaffolds for tissue engineering, tissue regeneration and repair, cancer therapy, etc. Biomaterials in general can be: (1) natural in origin such as many proteins from the extracellular matrix, natural polysaccharides or scaffolds presented in a blood clot or (2) synthetic, including polymers, ceramics, or peptides. In this review, we focus on the use of self-assembling peptide scaffolds as an innovative and reliable strategy to obtain platforms for cell and drug delivery to injured or diseased tissues and organs. This type of material is molecular by design and it develops spontaneously into nanofiber scaffolds with multiple uses. In particular, examples are given for applications in the area of cardiac repair and regeneration.