Synthetic Matrices for Stem Cell Growth and Differentiation

Synthetic Matrices for Stem Cell Growth and Differentiation

Funding Type: 
Tools and Technologies I
Grant Number: 
RT1-01053
Award Value: 
$599,404
Stem Cell Use: 
Embryonic Stem Cell
Status: 
Closed
Public Abstract: 
Statement of Benefit to California: 
Progress Report: 

Year 1

We proposed to develop novel, well-defined, synthetic extracellular matrices that support survival and proliferation of human embryonic stem cells. This is an important, unmet need in the field and development of such a substrate would aid in moving stem cell therapies to the clinic. In the first year of support, we have made significant progress. First, we characterized the cell surface receptors for matrix proteins on stem cells and identified specific proteins that will support adhesion and growth of the cells. Second, using an interdisciplinary approach, we developed a novel method to screen peptides from these proteins for their ability to support adhesion and proliferation of the stem cells. Finally, we identified a cyclic RGD peptide that supports growth of human embryonic stem cells. We are continuing to screen for new peptides that might be combined with cyclic RGD to optimize a scalable, inexpensive, clinically compliant substrate.

Year 2

We proposed to develop novel, well-defined, synthetic extracellular matrices that support survival and proliferation of human embryonic stem cells. This is an important, unmet need in the field and development of such a substrate would aid in moving stem cell therapies to the clinic. In the second year of support, we continued to make significant progress. Based on our characterization of cell surface receptors for matrix proteins on stem cells completed in the first year, we went on to test specific, purified proteins that will support adhesion and growth of the cells. In addition, we examined whether these substrates will support differentiation of retinal pigmented epithelial cells, an important, clinically relevant cell type that is currently in clinical trials for eye disease. Second, using an interdisciplinary approach, we developed novel hydrogels using click chemistry that support adhesion and proliferation of the stem cells. We continued studies of a cyclic RGD peptide that supports growth of human embryonic stem cells. We then went on to test a new synthetic surface containing another RGD peptide developed by collaborators at Geron and Corning. This surface proved to be efficient at supporting growth of undifferentiated hESC as well as differentiation of useful cell types. Thus we have identified two synthetic substrates we believe are scalable, inexpensive, and clinically compliant.

Year 3

We proposed to develop novel, well-defined, synthetic extracellular matrices that support survival and proliferation of human embryonic stem cells. This is an important, unmet need in the field and development of such a substrate would aid in moving stem cell therapies to the clinic. In the second year of support, we continued to make significant progress. Based on our characterization of cell surface receptors for matrix proteins on stem cells completed in the first year, we went on to test specific, purified proteins that will support adhesion and growth of the cells. In addition, we examined whether these substrates will support differentiation of retinal pigmented epithelial cells, an important, clinically relevant cell type that is currently in clinical trials for eye disease. Second, using an interdisciplinary approach, we developed novel hydrogels using click chemistry that support adhesion and proliferation of the stem cells. We continued studies of a cyclic RGD peptide that supports growth of human embryonic stem cells. We then went on to test a new synthetic surface containing another RGD peptide developed by collaborators at Geron and Corning, called synthemax. This surface proved to be efficient at supporting growth of undifferentiated hESC as well as differentiation of useful cell types. We also tested a new liquid version of synthemax. Thus we have identified two synthetic substrates we believe are scalable, inexpensive, and clinically compliant.

© 2013 California Institute for Regenerative Medicine