How does the physical environment affect stem cell fate and function?

Posted by Biome on 5th November 2013 - 2 Comments

The biochemical signals governing stem cell fate and function have been studied extensively, but the development of tissues relies on a complex interplay between these biochemical signals and physical influences that are much less well defined. These two inputs combine dynamically to control cell function through development and adult life. In recent years the fields of biology, medicine and engineering have come together to study the physical regulation of stem cells and its role in tissue development and regeneration – such understanding is key to the clinical translation of stem cell research.

With this in mind, Stem Cell Research & Therapy brings together a collection of articles providing the latest knowledge on the biophysical regulation of stem cells in tissue development in its special series ‘Physical influences on stem cells’, edited by Gordana Vunjak-Novakovic from Columbia University, USA. The series extends from probing the fundamental roles of physical regulation in cell function and tissue assembly, through to organ-specific advances and bioprocessing technologies. You can read more about developments in these fields in Biome’s Q&A with Vunjak-Novkoivc.

Mechanical and biophysical interactions in the stem cell niche. Image source: Conway and Schaffer, Stem Cell Research & Therapy, 2012, 3:50

Highlights of the series include Evelyn Yim and Michael Sheetz from the National University of Singapore reviewing components of the mechanotransduction pathway, and the role of biophysical cues such as substrate stiffness and topography in directing stem cell differentiation and cell fate. Introducing the mechanical and biophysical interactions within the stem cell niche itself, Anthony Conway and David Schaffer, from the University of California, Berkeley, USA, discuss the role of the extracellular matrix in the spatial organization of cues. Series Editor Gordana Vunjak-Novakovic and colleagues review the establishment of cell chirality, highlighting how the development of more accurate cellular microenvironments in in vitro cell chirality models may provide new opportunities for the study of left-right asymmetry and its importance in development and disease.

From cells to tissues, Sriram Manivannan and Celeste Nelson from Princeton University, USA, discuss the dynamic nature of tissue assembly in a review that compares and contrasts the development of two branched tissues: the tracheal network in Drosophila and the mouse mammary gland. A thorough comprehension of the mechanical properties of a tissue and the physical influences affecting its development, will facilitate progress in tissue engineering – a discipline that seeks to repair, improve, or replace biological tissue function.

Immunohistochemical image of human mesenchymal stem cell-PCL constructs cultured in an oscillating bioreactor. Stained for safranin-O. Image source: O'Conor et al, Stem Cell Research & Therapy, 2013, 4:61

The goal of engineering human tissues through harnessing stem cell differentiation is addressed throughout the series, in the context of vasculature, bone, cartilage and heart muscle. Janna Serbo and Sharon Gerecht from Johns Hopkins University, USA, present various biodegradable scaffolds for use in promoting angiogenesis. The role of mechanical cues in osteogenesis and the production of engineered bone grafts is reviewed by Warren Grayson and colleagues, also of Johns Hopkins University, while Farshid Guilak and colleagues from Duke University Medical Center, USA review the mechanical regulation of chondrogenesis (for more on this read our Q&A with first author Christopher O’Conor). Turning to matters of the heart, Milica Radisic and colleagues from the University of Toronto, Canada analyse the topological and electrical control of cardiac differentiation and assembly, and Wolfram Zimmermann from Georg-August University Göttingen, Germany, provides a biomechanical perspective on cardiogenesis.

Moving on from vital organs, Catherine Kuo from Tufts University, USA and colleagues look to fat, presenting novel research into how the cytoskeleton regulates the adipogenic differentiation of adipose-derived stem cells. These results may influence the development of adipose tissue models and in doing so aid future research into obesity.

The series also includes a more technological perspective to probing the physical influences on stem cells by looking at the development of scalable culture systems – a prerequisite for the therapeutic and diagnostic applications of stem cells. Todd McDevitt and colleagues from Georgia Institute of Technology and Emory University, USA, discuss the hydrodynamic modulation of pluripotent stem cells, studied in microfluidic and bioreactor systems, and how controlled hydrodynamic processes can be utilised for the high-throughput generation of cells.

For more insights into how physical parameters regulate stem cell differentiation and cell fate, take a look at the complete list of series articles.


The complete list of series articles:

Physical influences on stem cells