Exogenous BDNF and Chondroitinase ABC Consisted Biomimetic Microenvironment Regulates Survival, Migration and Differentiation of Human Neural Progenitor Cells Transplanted into a Rat Auditory Nerve

Ajay Kale, Ekaterina Novozhilova, Ulrica Englund-Johansson, Samuel I. Stupp, Björn Palmgren, Petri Olivius

Department of Chemistry, Materials Science and Engineering, and Medicine and Institute for BioNanotechnology in Medicine, Northwestern University, Chicago, USA.
Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Division of Otorhinolaryngology, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden.
Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden Division of Otorhinolaryngology, Department of Clinical and Experimental Medicine, University of Linköping, Linköping, Sweden Division of Otorhinolaryngology, Linköping University Hospital, Linköping, Sweden.
Department of Ophthalmology, Institution of Clinical Sciences in Lund, Lund University, Lund, Sweden.

DOI: 10.4236/nm.2014.52012                

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).

Keywords

Auditory Nerve, Brain Derived Neurotrophic Factor, Chondroitinase, Cochlear Nucleus, Human Neural Progenitor Cells, Transplantation, Transitional Zone, Sensorineural Hearing Loss

Conflicts of Interest

The authors declare no conflicts of interest.

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