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May 15, 2020

Organ-on-chip technology makes embryonic blood

In blood cell therapies, no cell type is more desired than hematopoietic stem progenitor cells. Therapies with these cells have brought cures to the Bubble Boy and HIV along with other blood diseases. Acquiring hematopoietic stem progenitor cells, however, relies on a decreasing pool of donors. In a new study, CiRA researchers report microfluidics chip technology to produce hematopoietic stem progenitor cells from iPS cells.

Blood is constantly replenishing. Hematologists estimate that the red blood cells in your body today were not there a month ago and will not be there a month from now. In classical hematology, throughout one's lifetime, all blood cells are generated by and only by hematopoietic stem progenitor cells, a type of cell that is made in the embryonic tissue known as the Aorta-Gonad-Mesonephros, or AGM.

"Scientists believe that the AGM is critical for modeling blood development and diseases. An artificial AGM could be a plentiful source of hematopoietic stem progenitor cells for cell therapies," says CiRA Associate Professor Megumu Saito, who managed the study.

One of the challenges in generating the AGM in the laboratory, according to Dr. Ryohichi Sugimura, another author of the study, is capturing an important stage that transitions iPS cells to hematopoietic stem progenitor cells.

"Hemogenic endothelial in the AGM undergoes an endothelial-to-hematopoietic transition. The endothelial-to-hematopoietic transition is considered a major determinant in the quality of the hematopoietic stem progenitor cells manufactured from iPS cells," he says.

To produce the AGM, the research team mixed hemogenic endothelial prepared from human iPS cells with purchased endothelial cells and mesenchymal stroma cells in the chip. The chip reconstituted the mixed cell types so that the mesenchymal stroma cells and hemogenic endothelial were separated from the endothelial cells by a porous membrane. However, the cells were injected into the cells separately, with the hemogenic endothelial introduced last. This injection series assured that the hemogenic endothelial only contacted the mesenchymal stroma cells in the chip.

"The porous membrane allowed us to mimic the organization of the AGM, with mesenchymal stroma cells in between the hemogenic endothelial and endothelial cells. Based on the hematopoietic stem progenitor cells we could acquire, our chip enabled the endothelial-to-hematopoietic transition," notes Sugimura.

The result was cells that showed the molecular properties of hematopoietic stem progenitor cells at numbers surpassing current systems.

"We expect this chip to be a powerful tool for assessing human developmental hematopoiesis and to derive various blood cells," says Sugimura.

Paper Details
  • Journal: Biomedical Microdevices
  • Title: Biomimetic aorta-gonad-Mesonephros-on-a-Chip to study human development hematopoiesis
  • Authors: Ryohichi Sugimura1, Ryo Ohta1, Chihiro Mori2, Alina Li1, Takafumi Mano1, Emi sano2, Kaori Kosugi2, Tatsutoshi Nakahata1, Akira Niwa1, Megumu K. Saito1, and Yu-suke Torisawa2,3
  • Author Affiliations:
    1. Department of Clinical Application, Center for iPS cell Research and Application, Kyoto University, Kyoto, Japan
    2. Department of Micro Engineering, Kyoto University, Kyoto, Japan
    3. Hakubi Center for Advanced Research, Kyoto University, Kyoto, Japan
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