Constructing stem cell microenvironments using bioengineering approaches

Abstract

Within the adult organism, stem cells reside in defined anatomical microenvironments called niches. These architecturally diverse microenvironments serve to balance stem cell self-renewal and differentiation. Proper regulation of this balance is instrumental to tissue repair and homeostasis, and any imbalance can potentially lead to diseases such as cancer. Within each of these microenvironments, a myriad of chemical and physical stimuli interact in a complex (synergistic or antagonistic) manner to tightly regulate stem cell fate. The in vitro replication of these in vivo microenvironments will be necessary for the application of stem cells for disease modeling, drug discovery, and regenerative medicine purposes. However, traditional reductionist approaches have only led to the generation of cell culture methods that poorly recapitulate the in vivo microenvironment. To that end, novel engineering and systems biology approaches have allowed for the investigation of the biological and mechanical stimuli that govern stem cell fate. In this review, the application of these technologies for the dissection of stem cell microenvironments will be analyzed. Moreover, the use of these engineering approaches to construct in vitro stem cell microenvironments that precisely control stem cell fate and function will be reviewed. Finally, the emerging trend of using high-throughput, combinatorial methods for the stepwise engineering of stem cell microenvironments will be explored.

Additive nanomanufacturing – A review

“…The growth is affected by cell adhesion to the substrate, chemical growth, small-molecule extracellular signalling and mechanical strain. 178 ANM technologies such as EHD Jet printing have the ability to print protein fibres with sub-cellular resolution 84 which could solve some of the biocompatibility problems and potentially accelerate growth in the field. The challenge will be to build biocompatible or living structures in three-dimensions rapidly for medical applications.…”

Shaping Pancreatic β-Cell Differentiation and Functioning: The Influence of Mechanotransduction

“…In vivo, cells are exposed to both micro-and nano-sized topographical stimuli; microscale signals (e.g., bundles of collagen fibers) can regulate collective cell behavior and migration. Beside them, the complex assembly of ECM molecules creates a nanoscale network that can influence single-cell behavior affecting cell proliferation, differentiation, and function [66,67].…”

Towards the design of 3D multiscale instructive tissue engineering constructs: Current approaches and trends

“…(Lutolf and Hubbell, 2005;Discher, et al, 2009;Lutolf, et al, 2009;Marklein and Burdick, 2010;Dvir, et al, 2011;Brafman, 2013;Costa and Mano, 2014;Han, et al, 2014) …”