Engineering mesenchymal stromal/stem cell-derived extracellular vesicles with improved targeting and therapeutic efficiency for the treatment of central nervous system disorders
Alexandra M. Iavorovschi1
Aijun Wang2
1.Surgical Bioengineering Laboratory,Department of Surgery,School of Medicine,University of California-Davis,Institute for Pediatric Regenerative Medicine,Shriners Hospitals for Children-Northern California,Sacramento,CA,USA2.Surgical Bioengineering Laboratory,Department of Surgery,School of Medicine,University of California-Davis,Institute for Pediatric Regenerative Medicine,Shriners Hospitals for Children-Northern California,Sacramento,CA,USA;Department of Biomedical Engineering,University of California,Davis School of Engineering,Davis,CA,USA
摘要：Treatment for central nervous system (CNS) disorders is known to be limit-ed by the low regenerative potential of neurons, and thus neurodegenerative insults became known as nearly irreversible ailments. Functional recovery for acquired CNS disorders, such as spinal cord injury (SCI), traumatic brain injury, ischemic stroke, Alzheimer's disease, Parkinson's disease, mul-tiple sclerosis (MS), and for congenital CNS abnormalities, such as spina bi-fida, is not spontaneous and effective treatments are limited to non-existent. Research in the past decades has proven the regenerative potential of stem cells, especially that of mesenchymal stromal/stem cells (MSCs) from various origins, such as bone marrow, placenta, and adipose tissue. Most notable MSC characteristics for their candidacy as CNS therapeutics include their immunomodulatory, angiogenic, and neuroprotective capa-bilities. For instance, in our previous studies using a fetal ovine model of spina bifida, we showed that placenta-derived MSCs (PMSCs) were able to improve neurological function by preserving spinal cord neurons (Wang et al., 2015). However, PMSCs did not persist following transplantation nor contributed to tissue regeneration by direct integration. Recently, using an in vitro neuronal injury/protection model, we showed that conditioned me-dia or extracellular vesicles (EVs) derived from PMSC cultures, suppressed caspase activity and rescued the apoptotic neurons as efficiently as the stem cells themselves (Kumar et al., 2019). Most recently, we further showed that EVs derived from PMSCs reduced DNA damage in oligodendroglia populations, increased myelination and improved motor function outcomes in an experimental autoimmune encephalomyelitis rodent model of MS. Furthermore, we found that the high-dose PMSC-EV treatment exerted similar clinical outcomes to the stem cells in the experimental autoimmune encephalomyelitis model, proving their potential as cell-free alternative therapeutics (Clark et al., 2019). Results from these studies indicate that it is likely MSCs confer their therapeutic effects via a paracrine mechanism, consisting of secreted therapeutic components, including EVs.
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论文发表日期：2020-12-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：2( 2235-2236 )