How do nearly six million Singaporeans live, work and play on an island that is barely visible on the world map? The solution is to grow the Lion City vertically. With space at a premium, local communities call high-density, high-rise buildings home.
According to biomaterials engineers, a similar approach might also work for housing stem cells.
From replacing damaged tissue in patients to modelling disease and developing new drugs, stem cells offer a plethora of clinical and research applications. The advent of human induced pluripotent stem cells (hiPSCs)–a method for genetically ‘rewinding’ adult cells into their embryonic state–has made stem cells even more versatile, but there is still room for improvement.
Inefficient processes for manufacturing large batches of clinical-grade hiPSCs have remained the weakest link. Cultivating them in monolayers on conventional flat culture dishes takes too long, produces unreliable results and requires excessive hands-on time. The result is poor-quality cells and an inefficient process unable to meet the demands of clinical and industrial applications.
A*STAR scientists led by Steve Oh, who was Director of the Stem Cell Bioprocessing Group at A*STAR’s Bioprocessing Technology Institute (BTI) during the time of the study have come forward with a potential solution: swirling, high-density quarters for stem cells.
Over the past two years, the team has been developing innovative ways for growing hiPSCs on microcarriers (MCs) suspended in culture. These spongy spheres maximise the surface area to volume ratio in large bioreactors enabling reduced wait times by a week and 30 to 50-fold more stem cell clones than the traditional static monolayer method.
“It’s a more flexible platform that better mimics the natural microenvironment for optimal cell growth,” explained Alan Lam, the co-corresponding author of this study.
This all-in-one platform for reprogramming, cultivating and differentiating-that the team named RepMC-has the potential to completely transform stem cell manufacturing.
“This method speeds up cellular reprogramming and allows for faster selection and expansion of high-quality hiPSC candidates for differentiation into specialised cells, such as heart and blood cells,” said Lam.
Before RepMC is ready for its clinical debut, some steps still require finetuning, such as ensuring the complete removal of microcarriers before stem cell implantation into patients. The team is also strategising ways to integrate the technology into current biomanufacturing frameworks to streamline future industry adoption.
The A*STAR-affiliated researchers contributing to this research are from the Bioprocessing Technology Institute (BTI).