Enabling the first human iPS trial of Parkinson’s disease with the MACSQuant® Tyto® Cell Sorter

Background

Professor Jun Takahashi’s famous laboratory at CiRA (Kyoto, Japan) is using the MACSQuant Tyto Cell Sorter for GMP-compliant sorting of iPSC-derived dopaminergic progenitors in a new trial for Parkinson’s disease.

hiPSC-derived neurons 
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The team’s current clinical trial, which aims to treat patients suffering from Parkinson’s disease with iPSC-derived dopaminergic neurons, arose from a primate-model study published in August 2017 in Nature. 

Practically the very definition of pioneering work, the human trial received massive attention in the field of regenerative medicine and far beyond, with dozens of related news articles*1 and reports*², thanks in no small part to the involvement of Nobel Laureate Shinya Yamanaka.

Challenge

So how did the MACSQuant Tyto Cell Sorter come to be involved and what difference did it make? 

Well, in the initial clinical trial Prof. Takahashi’s group made use of a conventional droplet-based cell sorting system to isolate the iPSC-derived progenitors its treatment required. However, both handling and sort performance left a lot to be desired: bad cellular yields and a literally exhaustive amount of hands-on time proved a massive burden for the operators, with sorting vials requiring exchange every 10 minutes for 16 straight hours.

Features of the cartridge-based cell sorting system
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After treating their first patient, the group began evaluating alternative clinical flow sorting solutions. 

They eventually selected the MACSQuant Tyto as it promised what no other alternative could offer: a fully closed system that makes use of gentle, sterile, microvalve-mediated, and operator-free cell sorting. 

A head-to-head comparison with the conventional droplet-based cell sorter followed to test those claims.
 

Results

You can judge for yourself from the data shown on Prof. Takahashi’s poster, presented at ISSCR 2019 in Los Angeles, USA. 

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Scientific poster
GMP-compliant microchip based cell sorting of IPSCs-derived dopaminergic progenitors

Daisuke Doi1, Jens Gaiser2, Daryl Grummitt2, Sebastian Knöbel2 and Jun Takahashi1

1Center for iPS cell Research and Application, Kyoto University, Kyoto, Japan
2Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany

Spoiler alert: post-sorting cell survival was increased with the MACSQuant Tyto, contributing to a higher yield of final cell product, whilst the estimated time to producing cells required for one patient was reduced by more than a third. 

In other words, more product was developed faster, allowing it to get to patients’ bedsides more quickly.