In brief

An all-in-one platform for reprogramming, cultivating and differentiating induced pluripotent stem cells uses microcarriers as a high-efficiency alternative for manufacturing quality cell products at scale.

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Stem cell megacities come to life

10 May 2023

A*STAR researchers develop a high-efficiency technique for scaling up stem cell manufacturing for clinical and research applications.

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).

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Lam, A.T.L., Ho, V., Vassilev, S., Reuveny, S. and Oh, S.K.W. An allied reprogramming, selection, expansion and differentiation platform for creating hiPSC on microcarrier. Cell Proliferation 55, 1-11 (2022) | article

About the Researcher

Alan Lam is a Staff Scientist at A*STAR’s Bioprocessing Technology Institute (BTI). Lam obtained his PhD in Biochemistry from the Chinese University of Hong Kong in 2003. In 2010, he joined Steve Oh’s group to develop scalable platforms for the mass production of human embryonic stem cells, human induced pluripotent stem cells, and human mesenchymal stem cells and their differentiated cells.

This article was made for A*STAR Research by Wildtype Media Group