Collagen hydrogel modified by bi-functional recombinant protein for transplantation of neural stem cells for the treatment of neurodegenerative disorder

• Grant number: 15/15826-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: February 01, 2017
• End date: July 31, 2022
• Field of knowledge: Interdisciplinary Subjects
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Alexander Henning Ulrich
• Grantee: Edgar Yuji Egawa
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases, AP.TEM
• Associated scholarship(s): 19/08107-5 - Collagen hydrogel modified by bi-functional recombinant protein for transplantation of neural stem cells for the treatment of neurodegenerative disorder, BE.EP.PD

Abstract

Neurodegenerative disorders such as Parkinson's and Alzheimer's diseases are characterized by the selective and progressive loss of neurons in the brain. There are no treatments to cure such devastating diseases. Current therapies only focus on treatment the symptoms in an attempt to improve the patient's quality of life. The neural stem cells replacement therapy is believed to be one of the most promising alternative for the development of a cure for these neurodegenerative disorders. Recent studies demonstrated the viability of neural stem cells (NSCs) as a source of cells for transplantation, although encouraging results have been demonstrated, some barriers such as low survival rate and compatibility of the cells still limit the results of the NSCs transplantation therapy. The use of scaffolds derived from extracellular matrices to overcome the aforementioned limitations have been proposed and demonstrated outstanding results, indicating that the progress of in biomaterials research may be the key point for the development of effective therapy. In this study a collagen scaffold modified by a bi-functional protein is proposed for the application as a biomaterial for the transplantation of NSCs for the treatment of Parkinson's disease. The recombinant bi-functional protein is designed to present the insulin-like growth factor (IGF-1) combined with a collagen binding domain. IGF-1 is a growth factor associated with the survival and differentiation of NSCs to neuron cells and protection of dopaminergic neurons. The collagen binding domain is responsible to attach the IGF-1 to the collagen fibers, generating a modified collagen scaffold that improves the cell survival and differentiation. The material will be developed and studied as an injectable collagen hydrogel that also induces NSCs differentiation to neuron cells. (AU)