Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord

Autor: Philip W. Askenase, Karen L. Lankford, Jeffery D. Kocsis, Katarzyna Nazimek, Krzysztof Bryniarski, Edgardo J. Arroyo
Rok vydání: 2018
Předmět:
0301 basic medicine
Pathology
Critical Care and Emergency Medicine
Cell Transplantation
Physiology
Exosomes
Nervous System
Culture Media
Serum-Free
Rats
Sprague-Dawley
White Blood Cells
Tetraspanin
Animal Cells
Immune Physiology
Medicine and Health Sciences
Medicine
Spinal Cord Injury
Spinal cord injury
Trauma Medicine
Staining
Multidisciplinary
biology
Stem Cells
Organ Size
Specimen preparation and treatment
3. Good health
medicine.anatomical_structure
Spinal Cord
Neurology
Cellular Structures and Organelles
Anatomy
Cellular Types
Antibody
Traumatic Injury
Research Article
medicine.medical_specialty
Imaging Techniques
Immune Cells
Science
Immunology
Spleen
03 medical and health sciences
Fluorescence Imaging
Animals
Vesicles
Spinal Cord Injuries
Blood Cells
business.industry
Macrophages
Therapeutic effect
Mesenchymal stem cell
DAPI staining
Biology and Life Sciences
Mesenchymal Stem Cells
Cell Biology
medicine.disease
Spinal cord
Microvesicles
Rats
Research and analysis methods
Neuroanatomy
030104 developmental biology
Culture Media
Conditioned
Nuclear staining
biology.protein
business
Neurotrauma
Neuroscience
Zdroj: PLoS ONE, Vol 13, Iss 1, p e0190358 (2018)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0190358
Popis: In a previous report we showed that intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) improved functional recovery after contusive spinal cord injury (SCI) in the non-immunosuppressed rat, although the MSCs themselves were not detected at the spinal cord injury (SCI) site [1]. Rather, the MSCs lodged transiently in the lungs for about two days post-infusion. Preliminary studies and a recent report [2] suggest that the effects of intravenous (IV) infusion of MSCs could be mimicked by IV infusion of exosomes isolated from conditioned media of MSC cultures (MSCexos). In this study, we assessed the possible mechanism of MSCexos action on SCI by investigating the tissue distribution and cellular targeting of DiR fluorescent labeled MSCexos at 3 hours and 24 hours after IV infusion in rats with SCI. The IV delivered MSCexos were detected in contused regions of the spinal cord, but not in the noninjured region of the spinal cord, and were also detected in the spleen, which was notably reduced in weight in the SCI rat, compared to control animals. DiR “hotspots” were specifically associated with CD206-expressing M2 macrophages in the spinal cord and this was confirmed by co-localization with anti-CD63 antibodies labeling a tetraspanin characteristically expressed on exosomes. Our findings that MSCexos specifically target M2-type macrophages at the site of SCI, support the idea that extracellular vesicles, released by MSCs, may mediate at least some of the therapeutic effects of IV MSC administration.
Databáze: OpenAIRE
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