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Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness.

Candiello J, Singh SS, Task K, Kumta PN, Banerjee I - J Biol Eng (2013)

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. pkumta@pitt.edu.

ABSTRACT

Background: 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. 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.

Results: This 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus

Change in endoderm gene expression during spontaneous differentiation of ESD3 embryonic stem cells due to changes in substrate stiffness. Endoderm marker TTR (A) demonstrated the highest amount of upregulation. Other endoderm markers demonstrated strong (B) upregulation also, while a small group of markers had very little to no upregulation (C).
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Figure 6: Change in endoderm gene expression during spontaneous differentiation of ESD3 embryonic stem cells due to changes in substrate stiffness. Endoderm marker TTR (A) demonstrated the highest amount of upregulation. Other endoderm markers demonstrated strong (B) upregulation also, while a small group of markers had very little to no upregulation (C).

Mentions: After qualitatively noting an increase in endoderm specific gene expression in response to changes in alginate substrate stiffness, we conducted a more rigorous study into endodermal differentiation (Figure‚ÄČ6).


Early differentiation patterning of mouse embryonic stem cells in response to variations in alginate substrate stiffness.

Candiello J, Singh SS, Task K, Kumta PN, Banerjee I - J Biol Eng (2013)

Change in endoderm gene expression during spontaneous differentiation of ESD3 embryonic stem cells due to changes in substrate stiffness. Endoderm marker TTR (A) demonstrated the highest amount of upregulation. Other endoderm markers demonstrated strong (B) upregulation also, while a small group of markers had very little to no upregulation (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3643844&req=5

Figure 6: Change in endoderm gene expression during spontaneous differentiation of ESD3 embryonic stem cells due to changes in substrate stiffness. Endoderm marker TTR (A) demonstrated the highest amount of upregulation. Other endoderm markers demonstrated strong (B) upregulation also, while a small group of markers had very little to no upregulation (C).
Mentions: After qualitatively noting an increase in endoderm specific gene expression in response to changes in alginate substrate stiffness, we conducted a more rigorous study into endodermal differentiation (Figure‚ÄČ6).

Bottom Line: 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.The 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA. pkumta@pitt.edu.

ABSTRACT

Background: 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. 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.

Results: This 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus