Concentrated conditioned media from adipose tissue derived mesenchymal stem cells mitigates visual deficits and retinal inflammation following mild traumatic brain injury

Kumar Abhiram Jha, Mickey Pentecost, Raji Lenin, Lada Klaic, Sally L. Elshaer, Jordy Gentry, John M. Russell, Alex Beland, Anton Reiner, Veronique Jotterand, Nicolas Sohl, Raja Shekhar Gangaraju

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Blast concussions are a common injury sustained in military combat today. Inflammation due to microglial polarization can drive the development of visual defects following blast injuries. In this study, we assessed whether anti-inflammatory factors released by the mesenchymal stem cells derived from adipose tissue (adipose stem cells, ASC) can limit retinal tissue damage and improve visual function in a mouse model of visual deficits following mild traumatic brain injury. We show that intravitreal injection of 1 µL of ASC concentrated conditioned medium from cells pre-stimulated with inflammatory cytokines (ASC-CCM) mitigates loss of visual acuity and contrast sensitivity four weeks post blast injury. Moreover, blast mice showed increased retinal expression of genes associated with microglial activation and inflammation by molecular analyses, retinal glial fibrillary acidic protein (GFAP) immunoreactivity, and increased loss of ganglion cells. Interestingly, blast mice that received ASC-CCM improved in all parameters above. In vitro, ASC-CCM not only suppressed microglial activation but also protected against Tumor necrosis alpha (TNFα) induced endothelial permeability as measured by transendothelial electrical resistance. Biochemical and molecular analyses demonstrate TSG-6 is highly expressed in ASC-CCM from cells pre-stimulated with TNFα and IFNγ but not from unstimulated cells. Our findings suggest that ASC-CCM mitigates visual deficits of the blast injury through their anti-inflammatory properties on activated pro-inflammatory microglia and endothelial cells. A regenerative therapy for immediate delivery at the time of injury may provide a practical and cost-effective solution against the traumatic effects of blast injuries to the retina.

Original languageEnglish (US)
Article number2016
JournalInternational journal of molecular sciences
Volume19
Issue number7
DOIs
StatePublished - Jul 11 2018

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Brain Concussion
adipose tissues
brain damage
stem cells
Conditioned Culture Medium
Stem cells
Mesenchymal Stromal Cells
blasts
Adipose Tissue
Brain
Blast Injuries
Stem Cells
Tissue
Inflammation
mice
cells
Anti-Inflammatory Agents
Chemical activation
activation
visual acuity

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Concentrated conditioned media from adipose tissue derived mesenchymal stem cells mitigates visual deficits and retinal inflammation following mild traumatic brain injury. / Jha, Kumar Abhiram; Pentecost, Mickey; Lenin, Raji; Klaic, Lada; Elshaer, Sally L.; Gentry, Jordy; Russell, John M.; Beland, Alex; Reiner, Anton; Jotterand, Veronique; Sohl, Nicolas; Gangaraju, Raja Shekhar.

In: International journal of molecular sciences, Vol. 19, No. 7, 2016, 11.07.2018.

Research output: Contribution to journalArticle

Jha, Kumar Abhiram ; Pentecost, Mickey ; Lenin, Raji ; Klaic, Lada ; Elshaer, Sally L. ; Gentry, Jordy ; Russell, John M. ; Beland, Alex ; Reiner, Anton ; Jotterand, Veronique ; Sohl, Nicolas ; Gangaraju, Raja Shekhar. / Concentrated conditioned media from adipose tissue derived mesenchymal stem cells mitigates visual deficits and retinal inflammation following mild traumatic brain injury. In: International journal of molecular sciences. 2018 ; Vol. 19, No. 7.
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