Pluripotent Stem Cells
Spatial Control of Signal Transduction
Inventors: William Murphy, Gregory Hudalla
The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing a novel approach for the delivery of growth factors and other biologically active signaling molecules.
Development of most tissue types involves a complex interplay of multiple growth factors in well defined locations, leading to controlled differentiation of precursor cells into mature, tissue-specific cell types. Ultimately, control over growth factor activity in a three-dimensional construct could allow the growth of hybrid tissues or organs with multiple cell types from a single stem cell precursor. However, existing approaches to growth factor presentation are not conducive to spatial patterning of growth factor activity or sustained growth factor activity, and can result in substantial loss of bioactivity due to harsh processing conditions.
UW-Madison researchers have developed a novel approach for the delivery of growth factors and other biologically active signaling molecules that allows for spatial control of signal transduction. Molecular handles (e.g., peptides or oligonucleotides) with an affinity for growth factors or other signaling molecules are attached to specific locations on a surface or within a matrix. The surface or matrix includes a translucent, biologically inert polymer backbone. Signaling molecules are drawn to the precisely desired location of the substrate or matrix by associating specifically, reversibly and non-covalently with the handles. The affinity of the molecular handle for the signaling molecule is tailored so that it selectively attracts the growth factor but does not bind so tightly that it blocks interaction of the growth factor with percursor cells. The signaling molecules can then be presented to precursor cells in locally high concentrations, mimicking complex developmental processes like organogenesis, which is particularly important in stem cell-based approaches to tissue regeneration.
- Novel drug delivery systems
- Bioactive substrates for microfluidics
- Bioactive coatings for biomedical implants/biosensors to enable in vivo tissue growth
- Smart materials for biocatalysis
- Affinity of a handle for a signaling molecule can be varied to allow for extensive tailoring of the sequestered signaling molecule’s availability on the surface or matrix.
- Allows the induction of cell differentiation, including stem cell differentiation
- Multiple signaling environments can occur in a single culture dish, allowing for high throughput screening of the effects of growth factors on stem cell differentiation.
- May be used to direct in vitro tissue growth in a three-dimensional matrix
- Takes advantage of endogenous growth factors produced by cells or present in small concentrations in the bloodstream
- Handles are relatively stable and easier to process than materials containing active growth factors.
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