Event Information
Title:
Biophysical and microfluidic manipulation of stem cell fate
Type:
Lecture
Sponsor:
The Clore Center for Biological Physics
Lecturer:
Prof. Justin Cooper White
Australian Institute for Bioengineering and Nanotechnology
Queensland, Australia
Date:
Tuesday, March 12, 2013
Time:
11:00
Location:
Michael and Anna Wix Auditorium, Jean Goldwurm 3D Visualization Theater
Contact:
Abstract:
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the ability to differentiate into all mesenchymal tissues, including bone, muscle, cartilage, tendon and fat. Pluripotent stem cells (hESC, iPSC) have the potential to form all tissues in our body. These cells are ideal candidates for a multitude of regenerative medicine applications, and further, for the development of new insights into disease etiology and progression and for cell-based drug discovery, screening and formulation design platforms.
The first part of this presentation will focus on our recent work aimed at elucidating how the mechanical property slate of a substrate may be explicitly tailored to manipulate stem cell fate decisions. Firstly, I will describe the complex interplay of substrate 18rigidity 19 and ligand type (e.g. collagens I and IV, laminin I and fibronectin) and availability on stem cell fate decisions. We show that substrate stiffness can be completely overridden by ligand-integrin interactions, and that substrate stiffness is not necessarily deterministic of stem cell fate. Secondly, I will show how influential time-dependent deformation or the 18creepiness 19 of a substrate can be (!). We have demonstrated that stem cells are explicitly sensitive to variations in the viscous properties of a viscoelastic substrate, not just the elastic properties. The 18creepier 19 the substrate, the more 18primed 19 the cells are for a whole host of fate decisions. Lastly, I will show how the nano-spatial arrangement of cell adhesion ligands on self assembled functional block copolymer surfaces (e.g., changes in lateral spacing of RGD peptides ranging from ~30 to 60 nm), can influence stem cell fate. We demonstrate that with increased lateral spacing of this peptide, we observe significant changes in cell morphology, motility and the ability of stem cells to maintain potency during expansion or otherwise undergo differentiation - lateral spacing of ligands can be tuned to preference lineage fate choices. These novel engineered substrates are enabling significant new insights into 18outside-inside signaling 19 and the underlying complex mechanisms involving mechanostransduction, integrin clustering and molecular pathways that regulate cellular tension.
In the second part of this presentation I will detail the development of, and associated novel insights provided by our cell-based diagnostic microbioreactor platforms for stem cell expansion and small molecule screening. These devices are proving to be very useful in screening microenvironmental cues (e.g. soluble factors, small molecules, ligands, oxygen) for optimum stem cell culture and expansion, tissue genesis and most recently, for drug toxicity, discovery and design.
Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the ability to differentiate into all mesenchymal tissues, including bone, muscle, cartilage, tendon and fat. Pluripotent stem cells (hESC, iPSC) have the potential to form all tissues in our body. These cells are ideal candidates for a multitude of regenerative medicine applications, and further, for the development of new insights into disease etiology and progression and for cell-based drug discovery, screening and formulation design platforms.
The first part of this presentation will focus on our recent work aimed at elucidating how the mechanical property slate of a substrate may be explicitly tailored to manipulate stem cell fate decisions. Firstly, I will describe the complex interplay of substrate 18rigidity 19 and ligand type (e.g. collagens I and IV, laminin I and fibronectin) and availability on stem cell fate decisions. We show that substrate stiffness can be completely overridden by ligand-integrin interactions, and that substrate stiffness is not necessarily deterministic of stem cell fate. Secondly, I will show how influential time-dependent deformation or the 18creepiness 19 of a substrate can be (!). We have demonstrated that stem cells are explicitly sensitive to variations in the viscous properties of a viscoelastic substrate, not just the elastic properties. The 18creepier 19 the substrate, the more 18primed 19 the cells are for a whole host of fate decisions. Lastly, I will show how the nano-spatial arrangement of cell adhesion ligands on self assembled functional block copolymer surfaces (e.g., changes in lateral spacing of RGD peptides ranging from ~30 to 60 nm), can influence stem cell fate. We demonstrate that with increased lateral spacing of this peptide, we observe significant changes in cell morphology, motility and the ability of stem cells to maintain potency during expansion or otherwise undergo differentiation - lateral spacing of ligands can be tuned to preference lineage fate choices. These novel engineered substrates are enabling significant new insights into 18outside-inside signaling 19 and the underlying complex mechanisms involving mechanostransduction, integrin clustering and molecular pathways that regulate cellular tension.
In the second part of this presentation I will detail the development of, and associated novel insights provided by our cell-based diagnostic microbioreactor platforms for stem cell expansion and small molecule screening. These devices are proving to be very useful in screening microenvironmental cues (e.g. soluble factors, small molecules, ligands, oxygen) for optimum stem cell culture and expansion, tissue genesis and most recently, for drug toxicity, discovery and design.