Plastic Surgery Research Council
Members Only  |  Contact  |  PSRC on Facebook

Back to Annual Meeting Program


MODULATION OF ER STRESS RESPONSES THROUGH AN IDO (INDOLEAMINE 2,3 DIOXYGENASE) DEPENDENT STEM CELL THERAPY IN A MURINE HIND-LIMB ISCHEMIA-REPERFUSION INJURY MODEL
Presenter: Mohamad Masoumy, MD
Co-Authors: Yu JC; Liu JY; Mozaffari MS; Baban B
Georgia Health

Ischemia-reperfusion (IR) injury involves crucial cellular and immune mechanisms which manifest in the pathogenesis of common diseases, from stroke to myocardial infarction, as well as in traumatic limb injuries and tissue flaps. Many studies report stem cell therapy (SCT) as a potential therapeutic measure for IR injury crediting improved angiogenesis and anti-inflammatory mechanisms for its efficacy. Endoplasmic reticulum (ER) stress response is where cellular stress induces aggregation of unfolded proteins which are then processed by the ER in order to maintain homeostasis and normal cellular function. When the inducing stress is prolonged, adaptive responses become overwhelmed and normal cellular function is overtaken by the initiation of apoptosis. In this study, we investigated the anti-inflammatory effects of SCT through IDO-mediated responses. Indoleamine 2, 3-dioxygenase (IDO) is the rate limiting enzyme in oxidative tryptophan catabolism and previous publications from our lab and others have shown it to play an important role in immune-modulation and anti-inflammation. Using a whole limb warm IR model with IDO +/+ (C57BL6) and IDO knockout (IDO-/- C57BL6) mice, we induced a 90 minute period of arterial inflow and venous outflow occlusion. 24 hours after injury, bone marrow derived stem cells (BMDSCs) were injecting intramuscularly and the effects studied over a period of 2 weeks. The BMDSCs used for SCT were isolated by targeting Sca1 through a magnetic-activated cell sorting technique. A combination of gross movement observations, magnetic resonance imaging, flow cytometry (markers used include Jc-1 and Annexin V) and immunohistochemistry (markers used include GRP-78 and GADD-153) were employed to examine the effects of SCT and recovery status. Our results show several key findings including: 1. Shortened recovery period with intramuscular BMDSCs injections. 2. BMDSC therapy likely mediates an anti-inflammatory benefit through an IDO dependent mechanism. 3. BMDSC therapy may also modulate ER stress and help maintain favor toward cellular homeostasis over initiation of apoptosis.


Back to Annual Meeting Program