Background: We succeeded to set up a rabbit model of Ischemia-Reperfusion (I/R) injury to test future candidate substance or plant extract that may have anti-oxidant action. To date many researchers reported that Mesenchymal Stem Cell (MSC) has immune modulating effect. We wanted to test the MSC's immune-modulating effect using our I/R injury model to elucidate their mechanism; if it is from anti-oxidant action of MSC or orchestrate effects from other factors. We also compared the efficacy between MSCs and vitamin E through our model (checked final gene production levels by PCR/RT-PCR)

Methods: 15 Rabbits are grouped three: Control, MSCs treated, and α-Tocopherol treated. Before these treatment all animals were stressed with I/R injuries. From the donor animal, we aspirate its Bone Marrow (BM), and purified and cultured. MSCs are defined with RT-PCR for the CD molecules. After treating as designed schedules, animals of each group were sacrificed to check kidneys for the gene products of TNF-α, VCAM, iNOS, HGF, VEGF and IL-10. Blood samples were serially drawn from each group for the test of creatinine (Cr) levels.

Results: 1)When BM-MSCs were injected to rabbits intravenously 24 hours before the I/R injury, right after I/R injury and 24 hours after the I/R injury with dose of 6 million cells, expression of inflammation- specific genes (TNF-α, VCAM and iNOS) were inhibited and expression of tissue regeneration- specific genes (HGF, VEGF and IL-10) were increased. 2) BM-MSCs decreased average value of serum Cr level of 0.41 & 2.81 mg/dL after 24 & 48 hours, respectively. 3) BM-MSCs had stronger anti-inflammatory & tissue regeneration effects than α-Tocopherol when vitamin E was orally administered to the rabbits 24 hours before the I/R injury, right after I/R injury and 24 hours after the I/R injury with dose of 268.5mg of α-tocopherol. 4) BM-MSCs inhibited expression of inflammation- specific genes (TNF-α, VCAM and iNOS) more than vitamin E. 5) BM-MSCs increased expression of tissue regeneration- specific genes (HGF, VEGF and IL-10) more than vitamin E. 6) BM-MSCs decreased the average value of serum creatinine level 0.37mg/dL more than vitamin E after 48 hours of re-perfusion. 7) Pathology of BM-MSCs treated group showed less severe than vitamin E and control group.

Conclusion:
 In I/R injury model, MSC was found to have their stronger anti-oxidant action than high dose of vitamin E, but they also have immune suppressive action.

CITATION INFORMATION: Jang J, Ri H, Hong I. Effect of Bone Marrow Derived Mesenchymal Stem Cells on Renal Ischemia-Reperfusion Injury in Rabbit. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress