Efficacy of Human Adipose Tissue-Derived Stem Cells on Neonatal Bilirubin Encephalopathy in Rats
- 337 Downloads
Kernicterus is a neurological syndrome associated with indirect bilirubin accumulation and damages to the basal ganglia, cerebellum and brain stem nuclei particularly the cochlear nucleus. To mimic haemolysis in a rat model such that it was similar to what is observed in a preterm human, we injected phenylhydrazine in 7-day-old rats to induce haemolysis and then infused sulfisoxazole into the same rats at day 9 to block bilirubin binding sites in the albumin. We have investigated the effectiveness of human adiposity-derived stem cells as a therapeutic paradigm for perinatal neuronal repair in a kernicterus animal model. The level of total bilirubin, indirect bilirubin, brain bilirubin and brain iron was significantly increased in the modelling group. There was a significant decreased in all severity levels of the auditory brainstem response test in the two modelling group. Akinesia, bradykinesia and slip were significantly declined in the experience group. Apoptosis in basal ganglia and cerebellum were significantly decreased in the stem cell-treated group in comparison to the vehicle group. All severity levels of the auditory brainstem response tests were significantly decreased in 2-month-old rats. Transplantation results in the substantial alleviation of walking impairment, apoptosis and auditory dysfunction. This study provides important information for the development of therapeutic strategies using human adiposity-derived stem cells in prenatal brain damage to reduce potential sensori motor deficit.
KeywordsStem cell Kernicterus Phenyl hydrazine Sulfisoxazole
The authors declare that they do not have any conflict of interests. This study was financially supported by the Grant No. 24317 from Iran University of Medical Sciences.
Compliance with Ethical Standards
Conflict of interest
No conflict of interest exists in the submission of this manuscript.
- Dubois SG, Floyd EZ et al (2008) Isolation of human adipose-derived stem cells from biopsies and liposuction specimens. Springer, Mesenchymal Stem Cells, pp 69–79Google Scholar
- lidong Z, Xiaoquan W, Tao C, Weiwei G, Chang L, Shiming Y (2013) Hyperbilirubinemia and auditory neuropathy. J Otol, 1002Google Scholar
- Loo DT (2011) In situ detection of apoptosis by the TUNEL assay: an overview of techniques. In: DNA damage detection in situ, ex vivo, and in vivo, Springer, Berlin, p 3–13Google Scholar
- Marcdante K, Kliegman RM et al (2010) Nelson essentials of pediatrics. Elsevier Health Sciences, LondonGoogle Scholar
- Ortega FD, Azpeitia GG et al (1997) Apertura reversible de la barrera hematoencefálica inducida por hipercapnia en hiperbilirrubinemia experimental. An Esp Pediatr 46:374–377Google Scholar