April 26, 2018
Kidney cells for cell therapy made in the lab
Patients with severe kidney diseases have only two options for treatment. One is dialysis therapy, which can now be done at the home but still requires two to three treatments a week with each taking several hours. The other is transplantation, which does not need lifelong treatment, but is available only to a small number of patients because of few donors. To compensate for the donor paucity, scientists have considered preparing and transplanting renal progenitor cells from iPS cells for cell therapy and kidney reconstruction. A new study by the laboratory of Prof. Kenji Osafune and published in Scientific Reports provides a new strategy for preparing these cells.
One of the challenges when preparing renal progenitor cells from iPS cells is separating them from other cells that emerge from the production process.
"We can separate renal progenitor cells by detecting nuclear marker gene expression, but the cells are not suitable for clinical therapy because the cells have been genetically modified to express fluorescent reporter proteins that monitor the nuclear marker expression," says Osafune.
Typically, processes that separate clinical-grade cells depend on antibodies that bind to surface antigens. The challenge for kidney cell therapies has been identifying which antigens represent renal progenitor cells.
"We know that renal progenitor cells express two nuclear markers, the genes Osr1 and Six2. We looked at cells that expressed these two genes and then mapped their surface markers. We found four antigens were crucial for renal progenitor identity," says Osafune.
The four antigens are CD9, CD140a, CD140b, and CD271. Osafune's team found that the transplantation of cells which expressed CD140a, CD140b, and CD271, but not CD9 could ameliorate acute kidney injury in mice.
All four antigens are expressed in the embryo, but the expression of CD9 is thought to occur at the earliest stages, while the others are expressed as the embryonic kidneys form.
Osafune stressed that marking renal progenitor cells by their antigens is a big step toward new cell therapies for kidney diseases.
"The isolation of iPSC-derived renal progenitor cells without genetic modification may give a substantial advantage in future cell therapies and disease modeling using patient cells," he said.
- Journal: Scientific Reports
- Title: Azusa Hoshina1, Tatsuya Kawamoto2, Shin-Ichi Sueta1, Shin-Ichi Mae1, Toshikazu Araoka1, Hiromi Tanaka1,7, Yasunori Sato3, Yukiko Yamagishi2, and Kenji Osafune1
- Author Affiliations:
- Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan
- Drug Discovery Research, Astellas Pharma Inc, Tsukuba, Japan
- Department of Global Clinical Research, Graduate School of Medicine, Chiba University, Chiba, Japan