title: The influence of sustained dual-factor presentation on the expansion and differentiation of neural progenitors in affinity-binding alginate scaffolds.
abstract: Biomaterials capable of controlling the release of multiple growth factors (GFs) could potentially promote the integration of co-transplanted neural progenitor cells (NPCs) and stimulate the plasticity and regenerability of the lesioned spinal cord. As a first step towards the employment of such a vehicle for cell therapy, this study examined the capability of an alginate-sulphate/alginate scaffold, able to capture and rigorously control the release of GFs, to promote the expansion and lineage differentiation of NPCs in vitro. Epidermal growth factor (EGF) and fibroblast growth factor-2 (bFGF) were affinity-bound to alginate-sulphate (200 ng/scaffold) and the bioconjugates were mixed with partially calcium-crosslinked alginate. NPCs isolated from 18 day-old rat embryo brains and seeded into the scaffold during preparation were found to proliferate and differentiate within the vehicle. A continuous release of both bFGF and EGF was noted for a period of 21 days. The concentrations of released GFs were sufficient to promote extensive NPC proliferation at initial cultivation times; the number of neurospheres in the scaffold was twice the number found in the 2D cultures supplemented with 20 ng/ml each factor every 3 days. Between days 10-14, when the GF concentrations had substantially declined, extensive cell migration from the neurospheres as well as lineage differentiation were noted in the scaffold; immunocytochemical analyses confirmed the presence of neurons, astrocytes and oligodendrocytes.The scaffold has a potential to serve as cell delivery vehicle, with proven capability to promote cell retention and expansion, while enabling NPC lineage differentiation in situ.
authors: Institute of Neurobiology, Slovak Academy of Sciences, Centre of Excellence for Brain Research, Kosice, Slovakia.
authors: Dasa
authors: D
authors: Cizkova
authors: Institute of Neurobiology, Slovak Academy of Sciences, Centre of Excellence for Brain Research, Kosice, Slovakia.
authors: Lucia
authors: L
authors: Slovinska
authors: Institute of Neurobiology, Slovak Academy of Sciences, Centre of Excellence for Brain Research, Kosice, Slovakia.
authors: Ivana
authors: I
authors: Grulova
authors: Laboratoire de Spectrométrie de Masse Biologique Fondamentale et Appliquée, Université de Lille 1, France.
authors: Michel
authors: M
authors: Salzet
authors: Institute of Animal Physiology, Slovak Academy of Sciences, Kosice, Slovakia.
authors: Stefan
authors: S
authors: Cikos
authors: The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors: Olga
authors: O
authors: Kryukov
authors: The Avram and Stella Goldstein-Goren Department of Biotechnology Engineering, Ben-Gurion University of the Negev, Beer Sheva, Israel.
authors: Smadar
authors: S
authors: Cohen
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D001921:Brain / Q000196:embryology; D002454:Cell Differentiation; D002460:Cell Line; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D004815:Epidermal Growth Factor / Q000378:metabolism; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D058953:Neural Stem Cells / Q000166:cytology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000737:chemistry; D054457:Tissue Scaffolds
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D013431:Sulfates; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D020723:Glucuronic Acid
keywords: alginate scaffold; alginate-sulphate; epidermal growth factor; fibroblast growth factor-2; neural progenitor cells; neurospheres