ヒトiPS細胞由来の近位尿細管細胞を用いたMPSにおけるP-gpとSGLT2の輸送能評価

Abstract

Proximal tubule plays an important role in reabsorption of nutrients and excretion of drugs. Such reabsorption and excretion processes are mediated by proteins known as transporters in the proximal tubule cells. To evaluate the transport of nutrients and xenobiotics in vitro, proximal tubule microphysiological systems (MPS) have been developed. However, conventional proximal tubule MPS employ cells derived from experimental animals or cells immortalized by genetic modification. Apparently, the expression levels of transporters are insufficient in these cells. In this study, we prepared MPS employing proximal tubular cells isolated from kidney organoids generated from iPS cells. In this MPS, we quantitatively evaluated the transport of SGLT2, which is responsible for glucose reabsorption, and P-gp, which is responsible for drug excretion. As a result, compared to MPS using immortalized cells, MPS using iPS cell-derived cells showed an approximately 1.6-fold improvement in the transport capacity. This indicates that we were able to produce an MPS that better reproduced reabsorption and excretion rates in vivo.