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167 MSC-Concentrated Supernatant: A Novel Therapeutical Approach in Inflammation-Induced Preterm Brain Injury?
  1. K Drommelschmidt1,
  2. S Prager1,
  3. I Bendix1,
  4. M Keller2,
  5. PA Horn3,
  6. AK Ludwig3,
  7. S Radtke3,
  8. B Giebel3,
  9. U Felderhoff-Müser1
  1. 1Department of Pediatrics I, University Children’s Hospital, Essen
  2. 2Childrens Hospital Passau, Passau
  3. 3Institute of Transfusion Medicine, University of Essen, Essen, Germany

Abstract

Background and aims Preterm brain injury of premature born infants is a main cause of disability and represents an enormous individual, familial and social burden. Up to 50% of these children suffer from disabilities such as cerebral palsy and cognitive disorders. The aetiology of brain injury has been considered to be multi-factorial. Factors such as hyperoxia or inflammation are important pathomechanism in the development of brain injury.

As infections and subsequent inflammation are almost unavoidable on NICUs, new anti-inflammatory approaches are needed. In differend experimental settings, mesenchymal stem cells (MSCs) show these anti-inflammatory abilities. Although intravenously administered MSCs get trapped in the lung, therapeutic effects in target tissue are detectable, thereby indicating paracrine mechanisms. Since MSC-supernatants contain molecules with immunosuppressive functions, such as the identified TSG-6, we wondered whether MSC supernatants contain additional, maybe synergistically acting factors. The objective of this study is to evaluate the effect of concentrated MSC-supernatant on brain damage caused by inflammation.

Methods Wistar rats were randomized in 4 groups (vehicle/vehicle, vehicle/concentrated MSC-supernatant, LPS/vehicle, LPS/concentrated supernatant). LPS (0.25mg/kg) was administered at p3, concentrated MSC-supernatant at p3 and p4. At p5, animals were transcardially perfused, brains were removed and snap-frozen for molecularbiological analysis.

Results At p5, LPS-treated animals show a marked increase in apoptosis, whereas additional treatment with concentrated MSC-supernatant results in a decrease in neural apoptosis.

Conclusions Concentrated MSC-supernatant showed promising effects on inflammation-induced brain damage in an experimental model of encephalopathy of prematurity.

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