Engineering of the embryonic and adult stem cell niches

Abstract

Context: Stem cells have the potential to generate a renewable source of cells for regenerative medicine due to their ability to self-renew and differentiate to various functional cell types of the adult organism. The extracellular microenvironment plays a pivotal role in controlling stem cell fate responses. Therefore, identification of appropriate environmental stimuli that supports cellular proliferation and lineage-specific differentiation is critical for the clinical application of the stem cell therapies.

Evidence acquisition: Traditional methods for stem cells culture offer limited manipulation and control of the extracellular microenvironment. Micro engineering approaches are emerging as powerful tools to control stem cell-microenvironment interactions and for performing high-throughput stem cell experiments.

Results: In this review, we provided an overview of the application of technologies such as surface micropatterning, microfluidics, and engineered biomaterials for directing stem cell behavior and determining the molecular cues that regulate cell fate decisions.

Conclusions: Stem cells have enormous potential for therapeutic and pharmaceutical applications, because they can give rise to various cell types. Despite their therapeutic potential, many challenges, including the lack of control of the stem cell microenvironment remain. Thus, a greater understanding of stem cell biology that can be used to expand and differentiate embryonic and adult stem cells in a directed manner offers great potential for tissue repair and regenerative medicine.

Keywords: Biocompatible Materials; Cell Differentiation; Cellular Microenvironment; Stem Cells.

Figure 1. Microarrays for Studying ES Cell Behavior

A) Scanning Electron Microscopy image of a PEG micro well array (left) and light microscopy image of ES cells cultured within a micro fabricated PEG micro well array of 75 μm diameter for 10 days (right) (36). The size and shape of EBs were controlled within an array of PEG micro wells. Scale bars are 200 µm; B) ECM microarray for studying ES cell differentiation (left) and bright-field micrograph of X-gal−stained ECM microarray conditions after 3 days of culture in retinoic acid (right) (88). The ECM array contained a combination of collagen I, III, laminin, and fibronectin. The scale bars are 1mm (left) and 250 µm (right).

Figure 2.. Human MSC Differentiation on Micro patterned Substrates

A) Cells cultured on small (1,024 µm2) and large (10,000 µm2) islands differentiated into adipocytes and osteoblasts respectively after 1 week. Lipids stain red and alkaline phosphatase stains blue. Scale bar is 50 µm; B) Differentiation efficiency of hMSCs plated onto 1024, 2025, and 10,000 μm2 islands after 1 week of culture in mixed media without aphidicolin.

Figure 3.. Retinal Progenitor Cells on Micro fabricated PMMA Scaffolds (87)

A) Micro fabricated PMMA scaffold containing pores with 11 µm diameter and 6 µm depths. Scale bar is 100 µm; B) Retinal progenitor cells on a porous PMMA membrane. The Dashed white line indicates a PMMA membrane; C) Cells migrated into the photoreceptor (ONL) and inner nuclear layer (INL) of the host retina. Green and blue shows green fluorescent protein (GFP) cells and cell nuclei. Scale bar is 50 µm