Kidney Week

Abstract: SA-PO435

Hypoxia-Preconditioned Mesenchymal Stem Cells Prevent AKI to CKD Progression

Session Information

• Development and Regenerative Medicine
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 500 Development, Stem Cells, and Regenerative Medicine

Authors

• Ishiuchi, Naoki, Hiroshima University Hospital, Hiroshima, Japan

Naoki Ishiuchi,

• Nakashima, Ayumu, Hiroshima University, Hiroshima, Japan

Ayumu Nakashima,

• Doi, Shigehiro, Hiroshima University Hospital, Hiroshima, Japan

Shigehiro Doi,

• Kanai, Ryo, Hiroshima University Hospital, Hiroshima, Japan

Ryo Kanai,

• Doi, Toshiki, Hiroshima University Hospital, Hiroshima, Japan

Toshiki Doi,

• Masaki, Takao, Hiroshima University Hospital, Hiroshima, Japan

Takao Masaki,

Background

Several studies have reported that mesenchymal stem cells (MSCs) promote regeneration of injured tissue via their paracrine activities, which are enhanced by hypoxic preconditioning. In this study, we examined the therapeutic efficacy of hypoxia-preconditioned MSCs for preventing acute kidney injury (AKI) to chronic kidney disease (CKD) progression using rat models of ischemia/reperfusion injury (IRI).

Methods

We injected rats through the abdominal aorta with hypoxia-preconditioned rat MSCs (1%O₂ rMSCs) or rat MSCs under normoxic conditions (21%O₂ rMSCs). We also administered hypoxia-preconditioned human MSCs (1%O₂ hMSCs) via the same procedure. In addition, we analyzed the conditioned medium from 1%O₂ hMSCs using ELISA kit and identified the humoral factor involved in anti-fibrotic abilities of MSCs.

Results

The administration of 1%O₂ rMSCs attenuated renal fibrosis induced by IRI more significantly than that of 21%O₂ rMSCs. 1%O₂ hMSCs also attenuated renal fibrosis and the anti-fibrotic effects of hypoxia-preconditioned MSCs were almost equivalent in bone marrow MSCs derived from rat and human. We also found that MSCs derived from rat and human were both observed in the kidney at day 21 post-IRI. Moreover, using flow cytometry, we confirmed that hypoxic preconditioning did not change the HLA expressions of MSCs. These results suggest that 1%O₂ hMSCs have low immunogenicity and may be a good candidate for allogeneic transplantation cell therapy. We also found that hypoxic preconditioning enhanced vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) secretion from MSCs. VEGF knockdown in 1% O₂ hMSCs by siRNA attenuated HGF secretion and the inhibition of TGF-β1 induced fibrotic changes in HK2 cells. It also weakened the suppression of renal fibrosis by 1%O₂ hMSCs in IRI models.

Conclusion

Our results indicate that hypoxia-preconditioned MSCs may be useful as an allogeneic transplantation cell therapy for preventing the progression of AKI to CKD.