The role of indoleamine 2,3 dioxygenase in beneficial effects of stem cells in hind limb ischemia reperfusion injury

Ischemia-Reperfusion (IR) injury of limb remains a significant clinical problem causing secondary complications and restricting clinical recovery, despite rapid restoration of blood flow and successful surgery. In an attempt to further improve post ischemic tissue repair, we investigated the effect...

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Bibliographic Details
Published in:PloS one 2014-04, Vol.9 (4), p.e95720-e95720
Main Authors: Masoumy, Mohamad, Yu, Jack, Liu, Jun Yao, Yanasak, Nathan, Middleton, Christopher, Lamoke, Folami, Mozaffari, Mahmood S, Baban, Babak
Format: Article
Language:English
Subjects:
Animal models
Animals
Apoptosis
Ataxin
Biology
Biology and Life Sciences
Blood
Blood flow
Bone marrow
Care and treatment
Cells, Cultured
Cellular structure
Complications
Cytokines
Cytometry
Dendritic cells
Diagnosis
Dioxygenase
Flow Cytometry
Hindlimb - pathology
Immunohistochemistry
Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Inflammation
Inflammatory response
Injuries
Ischemia
Laboratories
Lymphocytes
Magnetic Resonance Imaging
Medicine and Health Sciences
Metabolism
Metabolites
Mice
Mice, Inbred C57BL
Mice, Knockout
Recovering
Regulation
Reperfusion
Reperfusion injury
Reperfusion Injury - therapy
Research and Analysis Methods
Restoration
Risk factors
Rodents
Stem cell research
Stem cell transplantation
Stem cells
Stem Cells - physiology
Studies
Surgery
Toxoplasma gondii
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Summary:Ischemia-Reperfusion (IR) injury of limb remains a significant clinical problem causing secondary complications and restricting clinical recovery, despite rapid restoration of blood flow and successful surgery. In an attempt to further improve post ischemic tissue repair, we investigated the effect of a local administration of bone marrow derived stem cells (BMDSCs) in the presence or absence of immune-regulatory enzyme, IDO, in a murine model. A whole limb warm ischemia-reperfusion model was developed using IDO sufficient (WT) and deficient (KO) mice with C57/BL6 background. Twenty-four hours after injury, 5 × 105 cells (5×105 cells/200 µL of PBS solution) BMDSCs (Sca1 + cells) were injected intramuscularly while the control group received just the vehicle buffer (PBS). Forty-eight to seventy-two hours after limb BMDSC injection, recovery status including the ratio of intrinsic paw function between affected and normal paws, general mobility, and inflammatory responses were measured using video micrometery, flow cytometry, and immunohistochemistry techniques. Additionally, MRI/MRA studies were performed to further study the inflammatory response between groups and to confirm reconstitution of blood flow after ischemia. For the first time, our data, showed that IDO may potentially represent a partial role in triggering the beneficial effects of BMDSCs in faster recovery and protection against structural changes and cellular damage in a hind limb IR injury setting (P = 0.00058).
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0095720