Kidney regeneration using developing xenoembryo.

Abstract

We provide an overview of the recent progress in kidney regeneration with a particular focus on our previous study, which used developing xenoembryos for differentiating human mesenchymal stem cells (hMSCs). The principle of the methodology, recent advances, and limitations and challenges associated with kidney regeneration are outlined. Our primary study objective is to generate neokidney from dialysis patient-derived hMSCs. We previously showed that glial cell-derived neurotrophic factor-expressing hMSCs can differentiate into functional chimeric nephrons in developing mammalian embryos. Recently, we succeeded in eliminating xenotissues in transgenic oestrogen receptor-E2F transcription factor 1 (ER-E2F1) mice by introducing a suicide gene. We also showed MSCs derived from dialysis patients can be used for kidney regeneration. Blastocyst complementation strategy was used to generate chimeric nephrons by injecting mouse pluripotent stem cells into spalt-like transcription factor 1 (Sall1) knockout mouse blastocysts. Kidney tissue can be generated from human mouse pluripotent stem cells or MSCs by several methods. The size and function of regenerated kidney tissue do not meet the transplantation requirements for clinical applications. Although many outstanding problems remain for kidney regeneration, including ethical issues and the formation of chimeric structures, the neokidney generation exclusively from dialysis patient-derived cells is expected to be a reality in the future.