Abstract
BackgroundEmbryonic stem cells (ESCs) have been implicated to have tremendous impact in regenerative therapeutics of various diseases, including Type 1 Diabetes. Upon generation of functionally mature ESC derived islet-like cells, they need to be implanted into diabetic patients to restore the loss of islet activity. Encapsulation in alginate microcapsules is a promising route of implantation, which can protect the cells from the recipient’s immune system. While there has been a significant investigation into islet encapsulation over the past decade, the feasibility of encapsulation and differentiation of ESCs has been less explored. Research over the past few years has identified the cellular mechanical microenvironment to play a central role in phenotype commitment of stem cells. Therefore it will be important to design the encapsulation material to be supportive to cellular functionality and maturation.ResultsThis work investigated the effect of stiffness of alginate substrate on initial differentiation and phenotype commitment of murine ESCs. ESCs grown on alginate substrates tuned to similar biomechanical properties of native pancreatic tissue elicited both an enhanced and incrementally responsive differentiation towards endodermal lineage traits.ConclusionsThe insight into these biophysical phenomena found in this study can be used along with other cues to enhance the differentiation of embryonic stem cells toward a specific lineage fate.
Highlights
Embryonic stem cells (ESCs) have been implicated to have tremendous impact in regenerative therapeutics of various diseases, including Type 1 Diabetes
The alginate gel properties were meticulously tailored by calibrating the concentration of both alginic acid and the calcium ion crosslinker with, each gel type being subsequently further characterized by Atomic force microscopy (AFM) nano-indentation to determine the stiffness
After the 5 day time period we investigated the phenotypic commitment of the cells through real time reverse-transcription polymerase chain reaction (RT-PCR)
Summary
Embryonic stem cells (ESCs) have been implicated to have tremendous impact in regenerative therapeutics of various diseases, including Type 1 Diabetes. Upon generation of functionally mature ESC derived islet-like cells, they need to be implanted into diabetic patients to restore the loss of islet activity. Embryonic stem cells derived from the blastocyst of the embryo in its early development stages are characterized by their pluripotency. This pluripotent nature reserves the cell’s ability to differentiate into any of the primary germ layer precursor cells: ectoderm, mesoderm, and endoderm. These multiple germ layers give rise to all of the various cell types in the body, a functionality that is different from adult stem cells. Engler et al [6] in their pioneering work demonstrated that materials of similar mechanical attributes to those of native tissues associated with a cell type are most relevant for stem cell differentiation towards the corresponding phenotype
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