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October 30, 2018

Watching hearts heal

Attaching APEX2 to iPS cells allows CiRA researchers to observe a damaged heart heal after cell transplantation.

Cell transplantations are done to recover cells that have died, like in the case of a heart attack, to recover function of the damaged organ. However, once inside the body, doctors are challenged to trace the transplanted cells during recovery of the heart. A new study by CiRA researchers show that the attachment of APEX2 to iPS cells reveals the transplanted cells six months after transplantation in mouse hearts.

"We do not have methods that allow us to observe cells in nanoscale structure months or years after the transplantation," explains CiRA Associate Professor Yoshinori Yoshida, who is using iPS cells to develop cell therapies for the heart. "For the heart to function, it is important that electrical change is converted to mechanical construction in all the muscle cells. This includes forming specific structures like transverse tubules or dyads."

APEX2 is a molecular tag that operates with a wide range of imaging modalities, including electron microscopy and x-ray microtomography. CiRA scientists attached it to human iPS cells. The iPS cells were then differentiated into cardiac cells and transplanted into mice with defective hearts. Six months later, the hearts were removed for observation. The APEX2 tag made it clear which cells were from the original heart and which came from the transplanted cells.

"We found T-tubules and dyads formed by the transplanted cells in multimodality observation including X ray microtomography and electron microscope," notes Yoshida.

Importantly, the normal heart structures suggest that the addition of APEX2 did not affect the recovery, a major concern whenever labeling cells with a marker for imaging purposes.

"The heart depends on its cells contracting in coordination. It is essential that the transplanted cells mature to recover the heart. APEX2 allows us to observe this maturity," says Yoshida.

Paper Details
  • Journal: Biochemical and Biophysical Research Communications
  • Title: Nano-structural analysis of engrafted human induced pluripotent stem cell-derived cardiomyocytes in mouse hearts using a genetic-probe APEX2
  • Authors: Takeshi Hatani1,2, Shunsuke Funakoshi2, Thomas J Deerinck3,4, Eric A Bushong3,4, Takeshi Kimura1, Hiroshi Takeshima5, Mark H Ellisman3,4,6, Masahiko Hoshijima3,7, and Yoshinori Yoshida2
  • Author Affiliations:
    1. Department of Cardiovascular Medicine, Kyoto University, Kyoto, Japan
    2. Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
    3. Center for Research in Biological Systems, University of California, San Diego, La Jolla, California, USA
    4. National Cancer for Microscopy and Imaging Research, University of California, San Diego, La Jolla, California, USA
    5. Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
    6. Department of Neurosciences and Bioengineering, University of California, San Diego, La Jolla, California, USA
    7. Department of Medicine, University of California, San Diego, La Jolla, California, USA
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