Getting the right stuff: Controlling neural stem cell state and fate in vivo and in vitro with biomaterials

Abstract

Stem cell therapy holds great promises in medical treatment by, e.g., replacing lost cells, re-constitute healthy cell populations and also in the use of stem cells as vehicles for factor and gene delivery. Embryonic stem cells have rightfully attracted a large interest due to their proven capacity of differentiating into any cell type in the embryo in vivo. Tissue-specific stem cells are however already in use in medical practice, and recently the first systematic medical trials involving human neural stem cell (NSC) therapy have been launched. There are yet many obstacles to overcome and procedures to improve. To ensure progress in the medical use of stem cells increased basic knowledge of the molecular mechanisms that govern stem cell characteristics is necessary. Here we provide a review of the literature on NSCs in various aspects of cell therapy, with the main focus on the potential of using biomaterials to control NSC characteristics, differentiation, and delivery. We summarize results from studies on the characteristics of endogenous and transplanted NSCs in rodent models of neurological and cancer diseases, and highlight recent advancements in polymer compatibility and applicability in regulating NSC state and fate. We suggest that the development of specially designed polymers, such as hydrogels, is a crucial issue to improve the outcome of stem cell therapy in the central nervous system.

Two-component protein-engineered physical hydrogels for cell encapsulation

“…Because cells are highly sensitive to these nonphysiological conditions, these triggers can be irreversibly detrimental to the encapsulated cells and accompanying proteins; furthermore, these environmental conditions can be difficult to reproducibly control in clinical settings (15). Current cell injection techniques can result in substantial loss of transplanted viable cells (16,17).…”

The novel BTB/POZ and zinc finger factor Zbtb45 is essential for proper glial differentiation of neural and oligodendrocyte progenitor cells

“…[16][17][18][19] Upon mitogen (basic Fibroblast Growth Factor, FGF2) withdrawal, NSCs mainly form neurons and astrocytes, but oligodendrocyte differentiation can be enhanced by administration of thyroid hormone (T3), and efficient astrocytic differentiation can be obtained by treatment with interleukin-6 related compounds, such as CNTF, cardiotrophin-1 (CT-1) or leukemia inhibitory factor (LIF). 16,17,20,21 Several BTB/POZ-interacting co-regulators have been shown to repress differentiation of NSCs.…”

Induced Pluripotent Stem-Cell-Derived Neural Cell Types in Treatment of Stroke

“…Implantation into either the ipsilateral or contralateral hemisphere to the injury has resulted in beneficial effects, with evidence that cells are able to migrate across midline from the contra- lateral hemisphere towards the site of injury [7,62]. Injected neural progenitor cells display a predilection for injured tissues-a trait described as pathotropism [63,64]. Ischemic injured brain tissue can secrete a variety of signals such as stromal derived factor-1 (SDF-1) and monocyte chemotactic factor 1 (MCP-1), which attract cells, including iNSCs, carrying the receptors CXCR4, CXCR7, and CCR2 [65][66][67].…”