Mesenchymal stem cells as novel micro-ribonucleic acid delivery vehicles in kidney disease
1Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia.
Abstract:
MicroRNAs (miRNAs) are short single strands of RNA responsible for post-transcriptional regulation of gene expression and have been implicated in the pathogenesis of chronic kidney disease (CKD). Emerging evidence reports that miRNAs can reduce kidney fibrosis through regulation of targets associated with collagen and extracellular matrix accumulation. However, the development of miRNA therapies has been hampered by the lack of targeted and sustainable methods of systemic miRNA delivery. Mesenchymal stem cells (MSCs) provide a promising miRNA delivery platform to overcome toxicity, the potential for insertional mutations and the low efficiency of previous methods. MSCs are endogenously immunoprivileged and home to sites of inflammation. They also release trophic growth factors to modulate the immune system, alter the polarization of macrophages and provide renal protection and repair. The potential to engineer MSCs to express or overexpress miRNAs, released by exosomes, may enhance their natural functions. Clinical studies are already being conducted individually for the use of miRNAs in cancer and MSCs in diseases associated with CKD. Hence, the combination of miRNAs and MSCs may provide an unparalleled cell-based therapy for treating CKD.
Insights
MicroRNAs (miRNAs) show promise in treating chronic kidney disease (CKD) by reducing fibrosis. Combining miRNAs with mesenchymal stem cells (MSCs) offers a novel, effective cell-based therapy for CKD.
Area of Science:
- Biochemistry
- Molecular Biology
- Regenerative Medicine
Background:
- MicroRNAs (miRNAs) regulate gene expression and are implicated in chronic kidney disease (CKD) pathogenesis.
- miRNAs can mitigate kidney fibrosis by targeting collagen and extracellular matrix accumulation.
- Current miRNA therapies face challenges in targeted and sustainable systemic delivery.
Purpose of the Study:
- To explore the potential of mesenchymal stem cells (MSCs) as a delivery platform for miRNA-based therapies in CKD.
- To investigate how engineered MSCs can enhance miRNA delivery for renal protection and repair.
Main Methods:
- Utilizing mesenchymal stem cells (MSCs) for their immunoprivileged and inflammation-homing properties.
- Engineering MSCs to express or overexpress miRNAs for enhanced therapeutic effects.
- Leveraging exosomes released by MSCs for miRNA delivery.
Main Results:
- MSCs offer a promising platform to overcome limitations of traditional miRNA delivery, including toxicity and low efficiency.
- Engineered MSCs can enhance natural miRNA functions through exosome-mediated delivery.
- MSCs modulate the immune system, influence macrophage polarization, and promote renal repair.
Conclusions:
- The combination of miRNAs and MSCs presents a potentially unparalleled cell-based therapeutic strategy for CKD.
- This approach may overcome existing challenges in miRNA delivery and enhance therapeutic outcomes in chronic kidney disease.
