Control of stem cell fate by engineering their micro and nanoenvironment

Abstract

Stem cells are capable of long-term self-renewal and differentiation into specialised cell types, making them an ideal candidate for a cell source for regenerative medicine. The control of stem cell fate has become a major area of interest in the field of regenerative medicine and therapeutic intervention. Conventional methods of chemically inducing stem cells into specific lineages is being challenged by the advances in biomaterial technology, with evidence highlighting that material properties are capable of driving stem cell fate. Materials are being designed to mimic the clues stem cells receive in their in vivo stem cell niche including topographical and chemical instructions. Nanotopographical clues that mimic the extracellular matrix (ECM) in vivo have shown to regulate stem cell differentiation. The delivery of ECM components on biomaterials in the form of short peptides sequences has also proved successful in directing stem cell lineage. Growth factors responsible for controlling stem cell fate in vivo have also been delivered via biomaterials to provide clues to determine stem cell differentiation. An alternative approach to guide stem cells fate is to provide genetic clues including delivering DNA plasmids and small interfering RNAs via scaffolds. This review, aims to provide an overview of the topographical, chemical and molecular clues that biomaterials can provide to guide stem cell fate. The promising features and challenges of such approaches will be highlighted, to provide directions for future advancements in this exciting area of stem cell translation for regenerative medicine.

Untitled

“…They are easier to grow in cell culture and could find more diverse clinical applications, because they are pluripotent and can differentiate into cells of all three germ layers: endoderm, mesoderm and ectoderm. On the other hand, they could cause immune rejections and their proliferation and differentiation are more difficult to control [4]. Thus they could form tumors when introduced into patients unless made fully responsive to their environment.…”

Pluripotent Stem Cells and Their Dynamic Niche

“…It was shown that immobilised chemical cues are more effective than soluble factors. However, improved control over bioactivity, spacing and orientation of the immobilised growth factors is required to guide-/direct-specific stem cell differentiation [214]. Further studies investigating the effect of chemical signals on stem cell fate are summarised in …”

“…Micro-and nanopatterning techniques including soft lithography, electrospinning, layer-by-layer microfluidic patterning, three-dimensional printing, reactive ion etching and ion milling have resulted in the fabrication of scaffolds with controlled porosity, geometry and rigidity and texture [216][217][218]. The production of specific surface topography scales (nano, micro), types (ridges, pit, pillar, grooves) and distributions (random, regular) has enabled researchers to study the influence of topographical signals on stem cell differentiation [214]. Structural cues greatly affect gene expression as they determine cell shape, elongation, positioning of focal adhesion and cell-cell interactions [29,[219][220][221].…”

“…In addition, an individual biomaterial could exhibit various nanotopographies and gradients which would allow for further clinical applications [214]. Biomaterials are being designed and utilised to mimic the microenvironment and its cues stem cells experience in vivo.…”

“…Nano-and microtopography replicating the ECM signals have been shown to direct stem cell differentiation. ECM components linked to the biomaterials surface in form of small peptides or through the incorporation of growth factors have been successful approaches for guided stem cell differentiation and provide advanced stem cell-based clinical approaches [214,225] To overcome limiting factors for the clinical use of pluripotent stem cells, new culture systems based on advanced biomaterials are required which more closely mimic the native in vivo milieu and support application related stem cell fate decisions [225]. In summary, simplifying a complex three-dimensional stem cell niche into a two-dimensional biomaterial approach is a potent tool to study control machineries regulating stem cell biology.…”