New chemical probe helps scientists to sort stem cells

• Publication Information
• Media Coverage

March 7, 2014

Kyoto, Japan -- Researchers in Japan have discovered a chemical probe that becomes embedded selectively in human embryonic stem (hES) and induced pluripotent stem cells. The study, published in the journal Cell Reports, could be used to help scientists and doctors select cultivated cells used for regenerative medicine.

All cells in the human body originate from hES cells, which can be coaxed with various protein or chemical cocktails, to transform into specialized forms in the heart and blood. These coaxed cells can then replace damaged ones, offering hope to individuals who are currently suffering from illnesses such as heart failure.

However, not all cells respond to this coaxing and transplanting a mixture of transformed cells along with so-called stem cell holdouts poses potentially dangerous health risks including tumors.

"The problem is to ensure that patients only receive those cells which are beneficial," explained Kyoto University's Institute for Integrated Cell Material Sciences (iCeMS) professor and the study's principal investigator, Motonari Uesugi. "In other words, how can we eliminate potential troublemakers?

Uesugi led a team of researchers to distinguish stem cell holdouts from those committed to transformation using green fluorescent chemicals. In initial experiments testing over 300 compounds, they found one -- called KP-1 -- that selectively stayed in induced pluripotent stem cells.

"The reason why KP-1 sticks to these cells more than others is because they lack a family of membrane proteins that are responsible for expelling foreign molecules out," said Kazumitsu Ueda, another iCeMS professor involved in the study.

The scientists took advantage of this property to show that KP-1 was able to distinguish hES and induced pluripotent stem cells from human heart, blood, and liver cells.

"Adding KP-1 is cheaper than existing methods, reversible, and adjustable," added Ueda.

"We are hoping that KP-1 can one day be used as a tool for scientists conducting basic research, and by doctors treating diseases," said Uesugi.

Publication Information

A Chemical Probe that Labels Human Pluripotent Stem Cells
Nao Hirata^1,2,9, Masato Nakagawa^3,9, Yuto Fujibayashi^4,9, Kaori Yamauchi^5,9, Asako Murata^1,2,9, Itsunari Minami¹, Maiko Tomioka¹, Takayuki Kondo³, Ting-Fang Kuo^1,2, Hiroshi Endo^3,8, Haruhisa Inoue³, Shin-ichi Sato^1,2, Shin Ando^1,2, Yoshinori Kawazoe², Kazuhiro Aiba¹, Koh Nagata¹, Eihachiro Kawase⁵, Young-Tae Chang^6,7, Hirofumi Suemori⁵, Koji Eto³, Hiromitsu Nakauchi⁸, Shinya Yamanaka^1,3, Norio Nakatsuji^1,5, Kazumitsu Ueda^1,4, and Motonari Uesugi^1,2

Cell Reports | Published Online 7 March 2014 | DOI: 10.1016/j.celrep.2014.02.006

1. Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto 606-8501, Japan
2. Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan
3. Center for iPS Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan
4. Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan
5. Stem Cell Research Center, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
6. Department of Chemistry & MedChem Program of Life Sciences Institute, National University of Singapore, Singapore 117543, Singapore
7. Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, Agency for Science, Technology and Research (A*STAR), Singapore 138667, Singapore
8. Laboratory of Stem Cell Therapy, Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
9. These authors contributed equally to this work