Extracellular vesicle (EV)-based technologies represent a new advancement for disease treatment. EVs can be administered systemically, injected into the injury site directly, or applied locally in conjunction with bioengineered implantable scaffolds. Matrix-bound vesicles (MBVs), a special class of vesicles localized in association with the extracellular matrix (ECM), have been identified as critical bioactive factors and shown to mediate significant regenerative functions of ECM scaffolds. Loading EVs onto bioscaffolds to mimic the MBV-ECM complex has been shown superior to EV bolus injection in recent in vivo studies, such as in providing enhanced tissue regeneration, EV retention rates, and healing efficacy. Different types of natural biomaterials, synthetic polymers, and ceramics have been developed for EV loading, and these EV functionalized biomaterials have been applied in different areas for disease treatment. The EV functionalized scaffolds can be designed to be biodegradable, off-the-shelf biomaterials as a delivery vehicle for EVs. Overall, the bioengineered EV-loaded bioscaffolds represent a promising approach for cell-free treatment in clinical applications.
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder affecting over five million people globally and has no established cure. Current ADrelated treatments only alleviate cognitive and behavioral symptoms and do not address disease onset or progression, underlining the unmet need to create an effective, innovative AD therapeutic. Extracellular vesicles (EVs) have emerged as a new class of nanotherapeutics. These secreted, lipid-bound cellular signaling carriers show promise for potential clinical applications for neurodegenerative diseases like AD. Additionally, analyzing contents and characteristics of patient-derived EVs may address the unmet need for earlier AD diagnostic techniques, informing physicians of altered genetic expression or cellular communications specific to healthy and diseased physiological states. There are numerous recent advances in regenerative medicine using EVs and include bioengineering perspectives to modify EVs, target glial cells in neurodegenerative diseases like AD, and potentially use EVs to diagnose and treat AD earlier.
INTRODUCTION:
Spinal cord injury (SCI) is a devasting disease associated with severe disability and no effective cure. SCI involves a primary traumatic injury followed by a secondary injury characterized by inflammation, ischemia, and formation of a glial scar. Cellular therapies aim to minimize the secondary injury by protecting the remaining cells and promoting neuronal and glial regeneration. We have shown placental mesenchymal stromal cells (PMSCs) applied in utero improve ambulatory function and preserve motor neurons in an ovine model of spina bifida and have begun a first-in-human clinical trial for fetal spina bifida.
METHODS:
Female Sprague Dawley rats were given a right C5 hemi-contusion injury using an RWD Precise Impactor and 8 rats served as sham surgery controls. Immediately following injury, rats were treated with an ECM only (n = 9) or an ECM seeded with 3 x 105 PMSCs (PMSC-ECM, n = 11). Weekly motor function testing included Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale testing by blinded reviewers. After 8 weeks, rats were euthanized, and tissue collected for histology.
RESULTS:
Four second trimester PMSC cell lines were evaluated with our established anti-apoptotic neuroprotection assay and a single cell line was chosen based on increased neurite outgrowths. Within the PMSC-ECM group, rats had statistically significant improvement in their IBB scores between week 1 and week 8 (p = 0.002) compared to ECM only group, where rats did not show improvement (p = 0.063). When comparing IBB scores between groups at week 8, PMSC-ECM rats had a significantly higher IBB score compared to ECM only rats (p = 0.015).
CONCLUSION:
PMSCs improved motor function recovery in a rodent model of SCI. Further studies include immunohistochemical analysis and delivering PMSC derived exosomes as a cell-free treatment.
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