Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation

Abstract

Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were compared between olfactory ensheathing cells (OECs), Schwann cells (SCs), and bone marrow stromal cells (BMSCs). Neurite outgrowth from embryonic dorsal root ganglia (DRG) neurons was used to assess the efficacy of the hydrogels alone or in combination with cultured cells to promote axonal regeneration. The result showed that alginate hydrogel transformed OECs, SCs, and BMSCs into atypical cells with spherical shape and inhibited their metabolic activity. Combination of alginate hydrogel with fibronectin promoted only OECs proliferation. Alginate hydrogel also inhibited outgrowth of DRG neurites, although this effect was attenuated by addition of fibronectin, SCs, or BMSCs. In contrast, matrigel stimulated cell proliferation, preserved the typical morphological features of the cultured cells and induced massive sprouting of DRG neurites. Addition of cultured cells to matrigel did not further improve DRG neurite outgrowth. The present findings suggest that addition of extracellular matrix should be considered when engineering biosynthetic scaffolds on the basis of alginate hydrogels.

Compatibility of human fetal neural stem cells with hydrogel biomaterials in vitro

“…Growth factors such as TGF-β, basic fibroblast growth factor, insulin-like growth factor-1 and tissue plasminogen activator are also present (Novikova et al, 2003;Kleinman and Martin, 2005). Matrigel has previously been used in neuronal culture and has been shown to stimulate neurite outgrowth in vitro (Tisay and Key, 1999;Novikova et al, 2006).…”

Neural ECM mimetics

“…As the cross-linking multivalent cations gradually diffuse out from the gel, it slowly degrades and is excreted in urine. Alginate gels are frequently used as matrices for encapsulation of living cells and for the release of proteins (Novikova et al, 2006;Tobias et al, 2001Tobias et al, , 2005. In regeneration studies, alginate gels are often applied as cell carrier substances.…”

“…Alginate has been described to enhance neuronal sprouting and to decrease inhibitory cues after CNS trauma (Kataoka et al, 2004;Prang et al, 2006), but other studies have also reported a lack of axon growth stimulation mediated by alginate scaffolds (Estrada et al, 2014;Novikova et al, 2006). In vitro studies have even demonstrated that this biomaterial can inhibit the growth of dorsal root ganglion neurons and cause alteration of the phenotype of various different cell types (Novikova et al, 2006). This gel is, however, a quite suitable matrix for the encapsulation of cells with or even without further modification of the material.…”

“…As a biodegradable implant, Matrigel ™ resembles the complex extracellular environment found in many healthy tissues (Kleinman and Martin, 2005) and is widely used as a substrate for cell culture, which forms a nonporous hydrogel at physiological temperature. It has been described as a suitable matrix for tissue generation (Cassell et al, 2001) and has led to neuronal regeneration of varying degrees from only limited growth to extensive axonal sprouting in several studies (Iannotti et al, 2003;Novikova et al, 2006). Scaffolds of Matrigel ™ allow only limited axonal growth after spinal cord trauma (Estrada et al, 2014;Sakiyama-Elbert et al, 2012;Someya et al, 2008).…”

“…In combination with cellular transplants, especially Schwann cells, Matrigel ™ is a widely used biomaterial for neuronal regeneration, where it has been shown to obtain positive results regarding axonal regeneration after central and peripheral nerve injury (Fouad et al, 2005;Novikova et al, 2006;Rodriguez et al, 2000;Someya et al, 2008;Xu et al, 1995Xu et al, , 1997. In contrast to alginate, Matrigel ™ has not been found to alter the cellular morphology of olfactory ensheathing glia, Schwann cells, or bone marrow stem cells, and it has been reported to stimulate the growth of dorsal root ganglia in vitro (Novikova et al, 2006). Despite reported beneficial effects, the clinical use of Matrigel ™ remains questionable because of its tumor-derived origin and its batch-to-batch variability (Sakiyama-Elbert et al, 2012).…”