Actuating nanostructured polymer microcarriers for stem-cell derived cardiomyocyte expansion and maturation
| Title | Actuating nanostructured polymer microcarriers for stem-cell derived cardiomyocyte expansion and maturation |
|---|---|
| Acronym | CellBeat |
| Start date | 2025-04-01 |
| End date | 2028-03-31 |
| Sponsor | ERA4Health |
| Institution | University of Padova |
| Principal investigator | Milena Bellin
E-Mail: milena.bellin@unipd.it |
Associated cell lines
Project Description
Regenerative therapies require large quantities of functional cellular equivalents to restore, or repair injured or diseased native tissues. For example, replenishment of the cardiomyocyte (CM) pool following heart failure requires ~ 109 cells. Synthetic microcarriers applied in bioreactors provide unparalleled opportunities for large-scale CM manufacture in contrast to traditional Matrigel-based 2D culture. When derived from human induced pluripotent stem cells (hiPSCs), however, the functionality of the differentiated CMs is problematic for clinical application because of their fetal-like character. They are rudimentary, showing poor contractility and pose a risk of life-threatening arrhythmias. Thus, obtaining more mature hiPSC-derived CMs is urgently needed for safe implantation into cardiac patients. In 2D culture, active mechanical cues (e.g., stretch) have demonstrated the capacity to improve CM maturity. However, these protocols are challenging to implement in bioreactor culture with commercial microcarriers as the polymers are static. Herein, we aim to prepare the next generation of polymer microcarriers that actuate in response to light through responsive nanostructured liquid crystalline segments in their networks. They will be prepared by microfluidic methods with a bioactive nanofilament coating layer to promote hiPSC-CMs expansion. The effect of their actuation will be read out on hiPSC-CM maturation post-culture in small scale bioreactors evaluating molecular, electrophysiological, and functional CM readouts. These matured CMs will be evaluated in rodent and pig models of myocardial infarction, focusing on improving contractility and reducing arrhythmias in the large animal model. The beating CellBeat nanostructured microcarriers will be a game changer for this technology and open uncharted territory for bioreactor cell manufacture by imposing active mechanical forces that can be broadly applied to any cell type responsive to this cue in vivo.