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World J Stem Cells. Oct 26, 2013; 5(4): 124-135
Published online Oct 26, 2013. doi: 10.4252/wjsc.v5.i4.124
Engineering stem cell niches in bioreactors
Meimei Liu, Ning Liu, Ru Zang, Yan Li, Shang-Tian Yang
Meimei Liu, Ning Liu, Ru Zang, Shang-Tian Yang, William G Lowrie Department of Chemical and Biomolecular Engineering, Ohio State University, Columbus, OH 43210, United States
Yan Li, Department of Chemical and Biomedical Engineering, FAMU-FSU College of Engineering, Florida State University, FL 32310, United States
Author contributions: Liu M and Liu N prepared the original draft; Zang R contributed in writing and editing some sections in the manuscript; Li Y reviewed and revised the original draft; Yang ST conceived the idea, revised and finalized the manuscript.
Correspondence to: Shang-Tian Yang, PhD, Professor, William G Lowrie Department of Chemical and Biomolecular Engineering, Ohio State University, 140 west 19th Ave, Columbus, OH 43210, United States. yang.15@osu.edu
Telephone: +1-614-2926611 Fax: +1-614-2923769
Received: March 15, 2013
Revised: June 5, 2013
Accepted: July 4, 2013
Published online: October 26, 2013
Processing time: 231 Days and 3.1 Hours
Abstract

Stem cells, including embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells and amniotic fluid stem cells have the potential to be expanded and differentiated into various cell types in the body. Efficient differentiation of stem cells with the desired tissue-specific function is critical for stem cell-based cell therapy, tissue engineering, drug discovery and disease modeling. Bioreactors provide a great platform to regulate the stem cell microenvironment, known as “niches”, to impact stem cell fate decision. The niche factors include the regulatory factors such as oxygen, extracellular matrix (synthetic and decellularized), paracrine/autocrine signaling and physical forces (i.e., mechanical force, electrical force and flow shear). The use of novel bioreactors with precise control and recapitulation of niche factors through modulating reactor operation parameters can enable efficient stem cell expansion and differentiation. Recently, the development of microfluidic devices and microbioreactors also provides powerful tools to manipulate the stem cell microenvironment by adjusting flow rate and cytokine gradients. In general, bioreactor engineering can be used to better modulate stem cell niches critical for stem cell expansion, differentiation and applications as novel cell-based biomedicines. This paper reviews important factors that can be more precisely controlled in bioreactors and their effects on stem cell engineering.

Keywords: Stem cell engineering; Bioreactor; Differentiation; Microenvironment; Microfluidics

Core tip: Stem cells are promising cell sources for cell therapy, tissue engineering, drug discovery and disease modeling due to their ability of self-renewal and immense capability of lineage-specific differentiation. Bioreactor systems with engineered stem cell microenvironments, called “niches”, play an important role in deriving functional cell populations from stem cells. Some important factors and their effects on stem cell engineering in bioreactors are reviewed in this paper. The understanding of bioreactor regulation of stem cell niches is of great interest in developing novel biomedicines.