Features of Microsystems for Cultivation and Characterization of Stem Cells with the Aim of Regenerative Therapy

Abstract

Stem cells have infinite potential for regenerative therapy thanks to their advantageous ability which is differentiable to requisite cell types for recovery and self-renewal. The microsystem has been proved to be more helpful to stem cell studies compared to the traditional methods, relying on its advantageous feature of mimicking in vivo cellular environments as well as other profitable features such as minimum sample consumption for analysis and multiprocedures. A wide variety of microsystems were developed for stem cell studies; however, regenerative therapy-targeted applications of microtechnology should be more emphasized and gain more attractions since the regenerative therapy is one of ultimate goals of biologists and bioengineers. In this review, we introduce stem cell researches harnessing well-known microtechniques (microwell, micropattern, and microfluidic channel) in view point of physical principles and how these systems and principles have been implemented appropriately for characterizing stem cells and finding possible regenerative therapies. Biologists may gain information on the principles of microsystems to apply them to find solutions for their current challenges, and engineers may understand limitations of the conventional microsystems and find new chances for further developing practical microsystems. Through the well combination of engineers and biologists, the regenerative therapy-targeted stem cell researches harnessing microtechnology will find better suitable treatments for human disorders.

Simple In-House Fabrication of Microwells for Generating Uniform Hepatic Multicellular Cancer Aggregates and Discovering Novel Therapeutics

“…Various approaches have been proposed to generate MCAs, e.g., nonadherent plates [11], spinner culture [12], hanging drop [13] and microfabrication techniques [14,15]. The performance criteria generally depend on trade-offs in uniformity, throughput, cost and ease of usability in producing MCAs, as well as the integration of subsequent applications (reviewed by Ahn et al [16]. ) To meet the criteria, microwells produced by microfabrication have emerged as revolutionary tools over the past decade as they provide structurally confined microstructures for highly consistent and reproducible growth of MCAs (reviewed by Lee et al [17]. )…”

Engineering Stem Cell Self-organization to Build Better Organoids

“…Microwell-based cell culture substrates, generated for example via photolithography or micropatterning, offer a very straightforward approach for controlling cellular aggregation and organoid formation (Figure 2C, right panel). Microwells have been microfabricated using a large range of materials, including poly(dimethylsiloxane) (PDMS), PEG, or agarose hydrogels (Ahn et al, 2016), and have been used to control the size of aggregates in various cellular systems, such as EBs (Hwang et al, 2009;Vrij et al, 2016b), islet organoids (Candiello et al, 2018), salivary gland stem cell aggre-gates (Shin et al, 2018), and kidney organoids (Czerniecki et al, 2018). Microwells can also be used to decipher the optimal ratio of interacting cell types in co-culture, as was demonstrated for example with embryonic organoids termed ''blastoids'' that are formed by aggregating ESCs and trophoblast stem cells (Rivron et al, 2018).…”

Fluid dynamic design for mitigating undesired cell effects and its application to testis cell response testing to endocrine disruptors

“…A microfluidic system is an application of microelectromechanical systems (MEMS) technology whereby a fluidic-based experiment process is integrated at the microscale on a chip. This tool used for quantitative analysis and high-throughput assays has advantages such as low reagent consumption, low cost, and fast processing [ 1 ]. Especially, biochemical/mechanical stimuli are precisely controlled in the microfluidic chip to mimic the in vivo environment.…”

“…Especially, biochemical/mechanical stimuli are precisely controlled in the microfluidic chip to mimic the in vivo environment. Therefore, microfluidic-based cell culture devices, commonly referred to as organ-on-a-chip, are much better for observing the in vivo biological characteristics of cells than using conventional cell culture devices such as Petri dishes [ 1 ].…”

“…To mimic in vivo biomolecule transport using the microfluidic system, it is essential to satisfy the flow condition of Pe < 1 [ 10 ]. The diffusion-predominant molecular mixing maintains a stable concentration gradient of the biochemical in the microfluidic systems, which has been utilized in drug screening [ 1 ].…”