Optimization strategies of mesenchymal stem cell-based therapy for acute kidney injury

Abstract

Considering the high prevalence and the lack of targeted pharmacological management of acute kidney injury (AKI), the search for new therapeutic approaches for it is in urgent demand. Mesenchymal stem cells (MSCs) have been increasingly recognized as a promising candidate for the treatment of AKI. However, clinical translation of MSCs-based therapies is hindered due to the poor retention and survival rates as well as the impaired paracrine ability of MSCs post-delivery. To address these issues, a series of strategies including local administration, three-dimensional culture, and preconditioning have been applied. Owing to the emergence and development of these novel biotechnologies, the effectiveness of MSCs in experimental AKI models is greatly improved. Here, we summarize the different approaches suggested to optimize the efficacy of MSCs therapy, aiming at promoting the therapeutic effects of MSCs on AKI patients.

Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury

“…The mechanism of MSC/ASC-mediated protection is not fully understood. Originally, considered as a source of adult progenitor cells to mediate tissue repair, there are discrepant reports that injected MSCs home to the site of tissue injury [ 11 – 13 , 34 ]. In our own study, suprarenal injection of ASCs preserved kidney function in the absence of homing [ 15 ], suggesting that the therapeutic effect is mediated by factors liberated from ASC and/or modulation of distant cells or tissues, such as cells comprising the immune system.…”

All-trans retinoic acid pretreatment of mesenchymal stem cells enhances the therapeutic effect on acute kidney injury

“…However, low survival rates, low homing rates and ambiguous differentiation limit the therapeutic efficacy of MSCs. To overcome these limitations, various strategies have emerged to enhance the efficacy of stem cells, including drug pretreatment, gene modification, and biomaterial encapsulation [ 7 , 8 ]. Previous studies have shown that pharmacological enhancement of cellular bioactivity and improvement of the microenvironment for cell growth before transplantation is an effective pretreatment strategy for cellular therapy that can greatly benefit tissue repair [ 9 ].…”