Endothelial and Astrocytic Support by Human Bone Marrow Stem Cell Grafts into Symptomatic ALS Mice towards Blood-Spinal Cord Barrier Repair.
Sci Rep
; 7(1): 884, 2017 04 13.
Article
em En
| MEDLINE
| ID: mdl-28408761
ABSTRACT
Vascular pathology, including blood-CNS barrier (B-CNS-B) damage via endothelial cell (EC) degeneration, is a recently recognized hallmark of Amyotrophic Lateral Sclerosis (ALS) pathogenesis. B-CNS-B repair may be a new therapeutic approach for ALS. This study aimed to determine effects of transplanted unmodified human bone marrow CD34+ (hBM34+) cells into symptomatic G93A mice towards blood-spinal cord barrier (BSCB) repair. Thirteen weeks old G93A mice intravenously received one of three different doses of hBM34+ cells. Cell-treated, media-treated, and control mice were euthanized at 17 weeks of age. Immunohistochemical (anti-human vWF, CD45, GFAP, and Iba-1) and motor neuron histological analyses were performed in cervical and lumbar spinal cords. EB levels in spinal cord parenchyma determined capillary permeability. Transplanted hBM34+ cells improved behavioral disease outcomes and enhanced motor neuron survival, mainly in high-cell-dose mice. Transplanted cells differentiated into ECs and engrafted within numerous capillaries. Reduced astrogliosis, microgliosis, and enhanced perivascular end-feet astrocytes were also determined in spinal cords, mostly in high-cell-dose mice. These mice also showed significantly decreased parenchymal EB levels. EC differentiation, capillary engraftment, reduced capillary permeability, and re-established perivascular end-feet astrocytes in symptomatic ALS mice may represent BSCB repair processes, supporting hBM34+ cell transplantation as a future therapeutic strategy for ALS patients.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Células da Medula Óssea
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Astrócitos
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Células Endoteliais
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Esclerose Lateral Amiotrófica
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article