Abstract
BackgroundMesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been shown to have therapeutic potential for ischemic diseases and are considered an alternative to cell therapy. However, the low retention and poor stability of EVs post-transplantation in vivo remain obstacle prior to the clinical application of EVs.MethodsThis study was designed to investigate whether collagen matrix could increase the retention and stability of EVs and further improve the therapeutic effects in murine acute kidney injury (AKI) model. EVs were isolated from human placental MSCs (hP-MSC-EVs) and encapsulated in a collagen matrix. Then, we investigated whether collagen matrix can prolong the retention of EVs in vivo, further enhancing the therapeutic efficiency of EVs in AKI.ResultsOur results indicated that collagen matrix could effectively encapsulate EVs, significantly increase the stability of EVs, and promote the sustained release of EVs. Collagen matrix has improved the retention of EVs in the AKI model, which was proved by Gaussia luciferase (Gluc) imaging. The application of collagen matrix remarkably facilitated the proliferation of renal tubular epithelial cells in AKI compared with EVs alone. Moreover, collagen matrix could further augment the therapeutic effects of hP-MSC-EVs as revealed by angiogenesis, fibrosis and apoptosis, and functional analysis. Finally, we found that EVs play a therapeutic role by inhibiting endoplasmic reticulum (ER) stress.ConclusionsCollagen matrix markedly enhanced the retention of EVs and further augmented the therapeutic effects of EVs for AKI. This strategy for improving the efficacy of EVs therapy provides a new direction for cell-free therapy.
Highlights
Acute kidney injury (AKI) is a syndrome characterized by a rapid decrease in renal excretion with the risk of developing chronic kidney disease (CKD) and leading to renal failure [1, 2]
The culture supernatant was collected from Human placenta-derived mesenchymal stem cells (MSCs) (hP-MSCs) cultured in DMEM/F12 medium with extracellular vesicles (EVs)-free FBS (Gibco) for 48 h and EVs were isolated by differential centrifugations as previously described [29]
Isolation and characterization of EVs EVs were isolated from the supernatant of hP-MSCs via ultracentrifugation
Summary
Acute kidney injury (AKI) is a syndrome characterized by a rapid decrease in renal excretion with the risk of developing chronic kidney disease (CKD) and leading to renal failure [1, 2]. It is crucial for AKI therapy to regenerate the damaged kidney tissue and delay the progression of CKD to end stage renal disease (ESRD) [4,5,6]. Compared with stem cell therapy, EVs exhibit unique superiorities in safety issues. EVs derived from MSC have a low chance of eliciting immune responses, are highly stable, and are easy to store, avoiding the potential risk of ectopic transplantation [11, 12]. Mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) have been shown to have therapeutic potential for ischemic diseases and are considered an alternative to cell therapy.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
