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Prophylaxis against renal ischemia reperfusion injury in canine model: stem cell approach.

Login to Access Video or Poster Abstract: MP41-02
Sources of Funding: This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No 4713)

Introduction

To date, there is no evidence exploring the protective effects of stem cells on minimizing ischemia reperfusion injury in a higher animal model.

Methods

A group of 60 dogs were maintained to perform kidney injury model. Ischemia of 90 minutes were performed by open occlusion of left renal artery in 57dogs. Group I included 27 dogs that were treated with Bone marrow derived Mesenchymal Stem cells (BM-MSC) while group II (27 dogs) treated with adipose tissue derived Mesenchymal Stem cells (AT-MSC). Each group was divided into 3 subgroups (9 dogs each), according to the stem cell dose (5, 10, 15 X 10 in 500 µl volume) injected directly in the kidney cortex after reperfusion. 3 dogs were positive control without MSC treatment while 3 were sham-operated. All dogs were re-evaluated by renogram prior to sacrifice at 2 weeks, 2 and 3 months as well as histopathology of the investigated kidney. Pro-inflammatory markers CD95 and TNF were assessed using real time PCR.

Results

In group I, there was mean reduction of clearance of the investigated kidney by a mean of 78%,64% and 74% of the three used doses respectively at 2 weeks. At 3 months, these kidneys regained a mean of 84%, 92% and 72% respectively of its basal function. In group II, the reduction of clearance was much more modest with mean of 14%, 6% and 24% respectively at 2 weeks with more intense recovery of renal function by mean of 90%,100% and 76% respectively. Positive control showed more intense reduction of clearance by 90% at 2 weeks that regained 70% of basal function at 3 months. On histopathologic examination in group I, there was more significant tubular necrosis and delayed regeneration compared with group II. The histopathological insult was more pronounced in the control group with more delayed recoverability. Expressions of Pro-inflammatory markers were up regulated in both groups with higher and more sustained expression observed in group I.

Conclusions

Stem cell might protect against the ischemia reperfusion injury in canine model. AT-MSC would provide the best protective potentiality compared with BM-MSC.

Funding

This project was supported financially by the Science and Technology Development Fund (STDF), Egypt, Grant No 4713)

Authors
Yasser Osman
Sahar M. Hamed
Nashwa Barakat
Sherry Khater
Mahmoud Gabr
Ahmed Mosbah
Mohamed Gaballah
Atallah Shaaban
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