Hydrogels modified with IL4 or SDF1 mimicking peptides serve as a supportive environment for human iPSC-derived...

Skeletal muscles are characterised by substantial regenerative potential, which may be insufficient in case of, e.g., extensive muscle damage, changes accompanying muscle diseases or ageing. For this reason, different ideas are being tested to develop efficient and safe approaches to treat such muscles. Among them, strategies based on biomaterials and stem cells or their derivatives play an important role.

In the current study, we tested RADA16-I-based hydrogels, modified with custom-designed IL4 or SDF1 mimicking peptides, as a tool that allows development, maintenance or even an increase of myogenic differentiation potential of human myoblasts derived from induced pluripotent stem cells (iPSCs), which are considered a source of cells in therapies for skeletal muscles. Since the release of abovementioned peptides from hydrogels requires activity of metalloproteinases (MMPs) we first assessed the expression of MMPs in iPSC-derived myoblasts cultured on hydrogels. Then we determined the influence of hydrogels on proliferation, apoptosis, and differentiation of iPSC-derived myoblasts as well as their transcriptome and secretome.

We found that the hydrogels designed by us allowed proper proliferation, migration, and myogenic differentiation of hiPSC-derived myoblasts. The latter was even increased in case of hydrogels functionalised with either IL4 or SDF1 peptides. Importantly, none of the hydrogels tested induced neither apoptosis nor unwanted differentiation, i.e. adipogenic, chondrogenic or osteogenic, of hiPSC-derived myoblasts. In response to hydrogel presence, changes in the expression of factors, such as CXCL8, FREM2, ADAMTS16, CDH9, IRS4, FIBIN, or MLIP involved in angiogenesis, inflammatory mediation, cell adhesion, neurogenesis, and regulation of myogenic program were observed.

Obtained results indicate that hydrogels functionalised with IL4 or SDF1 peptides serve as a supportive environment for myoblasts derived from hiPSCs and increase features that are beneficial for myogenic/regenerative potential of these cells.