Cytoplasmic Extracts from Adipose Tissue Stromal Cells Alleviates Secondary Damage by Modulating Apoptosis and Promotes Functional Recovery Following Spinal Cord Injury

Spinal cord injury (SCI) typically results from sustained trauma to the spinal cord, resulting in loss of neurologic function at the level of the injury. However, activation of various physiological mechanisms secondary to the initial trauma including edema, inflammation, excito‐toxicity, excessive...

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Bibliographic Details
Published in:Brain pathology (Zurich, Switzerland) Switzerland), 2007-07, Vol.17 (3), p.263-275
Main Authors: Kang, Soo Kyung, Yeo, Jee Eun, Kang, Kyung Sun, Phinney, Donald G.
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - metabolism
Adipose Tissue - pathology
Animals
Apoptosis - drug effects
bcl-2-Associated X Protein - metabolism
Caspase 3 - metabolism
Cell Extracts - therapeutic use
Cells, Cultured
Cytoplasm - chemistry
Disease Models, Animal
Dose-Response Relationship, Drug
Hydrogen Peroxide - pharmacology
JNK Mitogen-Activated Protein Kinases - metabolism
Mitochondria - drug effects
Nerve Tissue Proteins - metabolism
Rats
Reactive Oxygen Species - metabolism
Recovery of Function - drug effects
Reverse Transcriptase Polymerase Chain Reaction - methods
Spinal Cord Injuries - drug therapy
Spinal Cord Injuries - pathology
Stem Cells - drug effects
Stromal Cells - pathology
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Summary:Spinal cord injury (SCI) typically results from sustained trauma to the spinal cord, resulting in loss of neurologic function at the level of the injury. However, activation of various physiological mechanisms secondary to the initial trauma including edema, inflammation, excito‐toxicity, excessive cytokine release and apoptosis may exacerbate the injury and/or retard natural repair mechanisms. Herein, we demonstrate that cytoplasmic extracts prepared from adipose tissue stromal cells (ATSCs) inhibits H2O2‐mediated apoptosis of cultured spinal cord‐derived neural progenitor cells (NPCs) resulting in increased cell survival. The ATSC extracts mediated this effect by decreasing caspase‐3 and c‐Jun–NH2‐terminal kinase (SAPK/JNK) activity, inhibiting cytochrome c release from mitochondria and reducing Bax expression levels in cells. Direct injection of ATSC extracts mixed with Matrigel into the spinal cord immediately after SCI also resulted in reduced apoptotic cell death, astrogliosis and hypo‐myelination but did not reduce the extent of microglia infiltration. Moreover, animals injected with the ATSC extract showed significant functional improvement of hind limbs as measured by the BBB (Basso, Beattie and Bresnahan) scale. Collectively, these studies show a prominent therapeutic effect of ATSC cytoplasmic extracts on SCI principally caused by an inhibition of apoptosis‐mediated cell death, which spares white matter, oligodendrocytes and neurons at the site of injury. The ability of ATSC extracts to prevent secondary pathological events and improve neurologic function after SCI suggests that extracts prepared from autologous cells harvested from SCI patients may have clinical utility.
ISSN:1015-6305
1750-3639
DOI:10.1111/j.1750-3639.2007.00070.x