Preconditioning strategies for improving the survival rate and paracrine ability of mesenchymal stem cells in acute kidney injury

Lingfei Zhao, Chenxia Hu, Ping Zhang, Hua Jiang, Jianghua Chen, Lingfei Zhao, Chenxia Hu, Ping Zhang, Hua Jiang, Jianghua Chen

Abstract

Acute kidney injury (AKI) is a common, severe emergency case in clinics, with high incidence, significant mortality and increased costs. Despite development in the understanding of its pathophysiology, the therapeutic choices are still confined to dialysis and renal transplantation. Considering their antiapoptotic, immunomodulatory, antioxidative and pro-angiogenic effects, mesenchymal stem cells (MSCs) may be a promising candidate for AKI management. Based on these findings, some clinical trials have been performed, but the results are contradictory (NCT00733876, NCT01602328). The low engraftment, poor survival rate, impaired paracrine ability and delayed administration of MSCs are the four main reasons for the limited clinical efficacy. Investigators have developed a series of preconditioning strategies to improve MSC survival rates and paracrine ability. In this review, by summarizing these encouraging studies, we intend to provide a comprehensive understanding of various preconditioning strategies on AKI therapy and improve the prognosis of AKI patients by regenerative medicine.

Keywords: acute kidney injury; mesenchymal stem cells; preconditioning strategy; survival and paracrine ability.

© 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Figures

Figure 1
Figure 1
The four main factors that limit the clinical efficacy of MSCs‐based therapy. (A) The low amount of engraftment. Most delivered MSCs are trapped in unwanted organs, such as liver, lungs, and spleen. Only 1% of transplanted cells can engraft into the target tissues. (B) Poor survival rate. It is reported that more than 80%‐90% of grafted cells will die within the first week after injection due to the harsh environment in vivo. (C) Impaired paracrine ability. The regenerative effect of MSCs largely relies on their paracrine action. Impaired MSC potency/biological activity in vivo has also been reported. (D) Delayed administration. Diagnosis of AKI is still on the basis of a rise in creatinine, which may cause a delayed administration of MSCs and induce the injured kidneys to the “point of no return”
Figure 2
Figure 2
Once injected into an injured tissue, MSCs face a harsh environment, including ROS, ischemia and anoikis, which may further induce cell apoptosis. Various preconditioning strategies, such as incubation with cytokines or chemical compounds, improvement of culture condition, thermosensitive hydrogel and genetic modification, can improve the survival rate and paracrine ability of MSCs and help them migrate to the target tissue in vivo

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