Abstract
Due to the safety issues and poor engraftment of mesenchymal stem cell (MSC) implantation, MSC-derived exosomes have been spotlighted as an alternative therapy for spinal cord injury (SCI). However, insufficient productivity of exosomes limits their therapeutic potential for clinical application. Moreover, low targeting ability of unmodified exosomes is a critical obstacle for their further applications as a therapeutic agent. In the present study, we fabricated macrophage membrane-fused exosome-mimetic nanovesicles (MF-NVs) from macrophage membrane-fused umbilical cord blood-derived MSCs (MF-MSCs) and confirmed their therapeutic potential in a clinically relevant mouse SCI model (controlled mechanical compression injury model). MF-NVs contained larger quantity of ischemic region-targeting molecules compared to normal MSC-derived nanovesicles (N-NVs). The targeting molecules in MF-NVs, which were derived from macrophage membranes, increased the accumulation of MF-NVs in the injured spinal cord after the in vivo systemic injection. Increased accumulation of MF-NVs attenuated apoptosis and inflammation, prevented axonal loss, enhanced blood vessel formation, decreased fibrosis, and consequently, improved spinal cord function. Synthetically, we developed targeting efficiency-potentiated exosome-mimetic nanovesicles and present their possibility of clinical application for SCI.
Highlights
Traumatic spinal cord injury (SCi) is a serious medical condition that causes permanent motor and sensory dysfunction
Recent studies have revealed that the therapeutic effects of mesenchymal stem cell (MSC) are mainly attributed to exosomes, which are a type of extracellular vesicles that contain RNAs and proteins and serve as a nanocarrier of the biomolecules between cells [14,15]
Mice were randomized into four groups: (i) sham group, (ii) the group treated with phosphatebuffered saline (PBS) following static weight compression spinal cord injury (SCI), (iii) the group treated with N-NV, and (iv) the group treated with MF-NVs
Summary
Traumatic spinal cord injury (SCi) is a serious medical condition that causes permanent motor and sensory dysfunction. The therapeutic efficacy of implanted MSCs can be limited because of the poor survival and the possibility of the differentiation into other cell types including chondrocytes and osteoblasts [12]. To produce sufficient amounts of exosomes from MSCs for clinical applications, cultures of a large number of MSCs and long-term cultures are required To overcome these obstacles, recent studies have developed exosome-mimetic nanovesicles (NVs). Despite the advantages of NVs and exosomes over MSCs therapies, NVs and exosomes do not have the ability to target to diseased organs after systemic injection, which limits the therapeutic efficacy of NV or exosome therapies [32,33]. MF-NVs contain integrin α4 and β1 originated from macrophage membrane and may improve the efficiency of NVs targeting to ischemic and inflammatory organs such as the injured spinal cord. Inint.jeJ.cMtiool.nSicni.t2o02m0,i2c1e, 4w18i5th SCI, MF-NVs showed better spinal cord targeting efficiency and therap3eouf 2ti0c efficacy than N-NVs
Sign-in/Register to view highlights & summary 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.
