TITLE:
Exogenous BDNF and Chondroitinase ABC Consisted Biomimetic Microenvironment Regulates Survival, Migration and Differentiation of Human Neural Progenitor Cells Transplanted into a Rat Auditory Nerve
AUTHORS:
Ajay Kale, Ekaterina Novozhilova, Ulrica Englund-Johansson, Samuel I. Stupp, Björn Palmgren, Petri Olivius
KEYWORDS:
Auditory Nerve, Brain Derived Neurotrophic Factor, Chondroitinase, Cochlear Nucleus, Human Neural Progenitor Cells, Transplantation, Transitional Zone, Sensorineural Hearing Loss
JOURNAL NAME:
Neuroscience and Medicine,
Vol.5 No.2,
April
30,
2014
ABSTRACT: Current putative
regeneration oriented studies express possible role of stem cell based implantation
strategy in the restoration of fundamental perception of hearing. The present
work utilizes a rat auditory nerve (AN) directed transplantation of human
neural progenitor cells (HNPCs) as a cell replacement therapy for impaired
auditory function. Groups of b-bungarotoxin
induced auditory function compromised female rats were used to transplant HNPCs
in the nerve trunk. In the treatment groups, brain derived neurotrophic factor
(BDNF), peptide amphiphile nanofiber bioactive gel (Bgel) and Chondroitinase
ABC (ChABC), a digestive enzyme that cleaves the core of chondroitin sulphate
proteoglycans, were added along with HNPCs while the control groups were with
PA inert gel (Igel) and devoid of ChABC. Six weeks post transplantation
survival, migration, and differentiation of HNPCs were studied and compared.
The groups treated with BDNF and Bgel showed improved survival and
differentiation of transplanted HNPCs while the ChABC treated group showed
significant migration of HNPCs along the AN and elongation of neuronal fibers
along the nerve towards the cochlear nucleus (CN) which was characterized by
immunocytochemical markers for human Nuclei (HuN), human mitochondria (HuM) and
neuronal β-tubulin (Tuj1). These
findings show that addition of BDNF and ChABC consisted Bgel environment
facilitated HNPC survival, migration and differentiation along the transplanted
rat AN towards the CN. This transplantation strategy provides unique
experimental validation for futuristic role of cell based biomaterial consisted
neurotrophic factor application in clinically transferable treatment of sensorineural
hearing loss (SNHL) along with cochlear implants (CI).