Human adipose-derived stem cell treatment modulates cellular protection in both in vitro and in vivo traumatic brain injury models.
J Trauma Acute Care Surg
; 84(5): 745-751, 2018 05.
Article
in En
| MEDLINE
| ID: mdl-29251705
ABSTRACT
BACKGROUND:
Traumatic brain injury (TBI) is a common cause of morbidity and mortality in the civilian population. The purpose of this study was to examine the effect(s) of adipose-derived stem cell (ASC) treatment on cellular and functional recovery in TBI via both in vitro and in vivo methods.METHODS:
Cultured neuroblastoma cells, SH-SY5Y, were scratched to mimic TBI in an in vitro model. The effect of ASC-conditioned medium (CM) on cell death, mitochondrial function, and expression of inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin 1ß [IL-1ß], and IL-6), as well as apoptosis marker FAS, was measured. In our in vivo model, Sprague-Dawley rats underwent TBI via a frontal, closed-head injury model. Animals randomly received either intravenous human-derived ASCs or intravenous saline within 3 hours of injury and were compared with a sham group. Functional recovery was evaluated via accelerating Rotarod method. On post-TBI Day 3, brain tissue was harvested and assessed for cellular damage via enzyme-linked immunosorbent assay for TNF-α, as well as immunohistochemical staining for ß-amyloid precursor protein (ß-APP).RESULTS:
Our in vitro data show that ASC treatment imparted reduced cell death (ratio to control 1.21 ± 0.066 vs. 1.01 ± 0.056, p = 0.017), increased cell viability (ratio to control 0.86 ± 0.009 vs. 1.09 ± 0.01, p = 0.0001), increased mitochondrial function (percentage of control 78 ± 6% vs. 68 ± 3%), and significantly decreased levels of inflammatory cytokine IL-1ß. In our in vivo study, compared with TBI alone, ASC-treated animals showed no difference in functional recovery, lower levels of expressed TNF-α (ratio to total protein, 0.47 ± 0.01 vs. 0.67 ± 0.04; p < 0.01), and lower levels of ß-amyloid precursor protein (fluorescence ratio, 0.43 ± 0.05 vs. 0.69 ± 0.03; p < 0.01).CONCLUSIONS:
Adipose-derived stem cell treatment results in improved cell survival, decreased inflammatory marker release, and decreased evidence of neural injury. No difference in functional recovery was seen. These data suggest the potential for ASC treatment to aid in cellular protection and recovery in neural cells following TBI.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stem Cells
/
Adipocytes
/
Stem Cell Transplantation
/
Brain Injuries, Traumatic
/
Nerve Regeneration
/
Neurons
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
J Trauma Acute Care Surg
Year:
2018
Document type:
Article