Stem cells are essentially the raw materials of our body – cells that give rise to all other cells and tissues with specialized functions. Conversion into specific cells occurs through a process called “differentiation”, in which stem cells divide to form daughter cells. This lends itself to practical applications in regenerative therapy, where functional healthy cells generated from stem cells can be used to heal wounds and cellular damage in our body.
However, things are easier said than done. The differentiation of stem cells in the laboratory requires careful preparation and the addition of differentiation factors to cell culture medium, a laborious and time-consuming process. Moreover, it largely depends on the skill of the researcher. In light of this, a new platform that facilitates a stable supply of differentiators over a long period of time is highly desirable.
In a new study, Korean researchers, led by Associate Professor Tae-Hyung Kim of Chung-Ang University’s School of Integrative Engineering, have come up with an ingenious solution. They developed a novel platform based on metallic organostructures (MOFs), hybrid crystalline porous materials constructed using metal ions and organic ligands (ions/molecules attached to the metal ion). Due to their porous nature, MOFs are excellent at trapping and releasing molecules of interest over a long period of time. This gave the team the idea of using MOFs to store and release the biocompatible nanoparticles needed for stem cell differentiation. This document was posted on April 20, 2022 and has been published in Volume 8, Number 16 of the journal Science Advances on April 20, 2022.
In their study, the team chose neural stem cells as a proof of concept and embedded nanoparticles loaded with retinoic acid, an essential component for neuronal differentiation, into the nanocrystalline MOF, nUiO-67. There was, however, a question to consider. “Adding nanoparticles directly to cell culture medium can lead to safety issues when used for therapeutic purposes and can also damage nanoparticle structures due to the presence of redox enzymes and reactive species. oxygen (ROS) in the intracellular environment,” says Dr. Kim.
To circumvent this problem, the team separated the stem cells from the MOFs by creating a periodic pattern of arrays of nanowells using a technique called “laser interference lithography”.
By optimizing these nanowell arrays so that each array picks up a single MOF, the team developed the platform called “nanopit arrays embedded in single metal-organic framework (MOF) nanoparticles (SMENA)” that could automatically convert stem cells into neurons.
SMENA offered two major advantages over the conventional method of stem cell differentiation in vitro. First, it avoided all the complex experimental steps and typical issues related to cell contamination and batch-to-batch variation. Second, and surprisingly, the continuous and stable supply of differentiation factors enabled accelerated differentiation, resulting in approximately 40-fold higher expression of neuronal cell markers (indicating neuron generation) compared to that of standard protocols. .
These findings have excited the team about SMENA’s future prospects. “The platform developed in our study could facilitate and accelerate the use of various stem cell sources for clinical applications and drug screening. The functional cells produced by SMENA can be used to treat various diseases and disorders, including Alzheimer’s and Parkinson’s disease,” speculates Dr Kim. The article was also recently featured as a research highlight in Nature Reviews Materials by Associate Editor, Charlotte Allard.
We certainly hope that Dr. Kim’s visions of SMENA will come true soon!
Author: Yeon-Woo Cho1Seo Hyeon Jee2Intan Rosalina Suhito1Jeong Hyeon Lee1Chun Gwon Park3,4Kyung Min Choi 2.5Tae Hyung Kim1
1School of Integrative Engineering, Chung-Ang University
2Department of Chemical and Biological Engineering, Sookmyung Women’s University
3Department of Biomedical Engineering, SKKU Institute
for Convergence, Sungkyunkwan University (SKKU)
4Department of Precision Healthcare Intelligent Convergence, SKKU Institute for Convergence, Sungkyunkwan University (SKKU)
5LabInCube Co. Ltd.
About Chung-Ang University
Chung-Ang University is a private comprehensive research university located in Seoul, South Korea. It was started as a kindergarten in 1918 and gained university status in 1953. It is fully accredited by the Ministry of Education of Korea. Chung-Ang University conducts research activities under the slogan “Justice and Truth.” Its new vision to end its 100 years is “The world leader in creation”. Chung-Ang University offers undergraduate, postgraduate, and doctoral programs, which encompass a law school, a management program, and a medical school; it has 16 undergraduate and graduate schools each. Chung-Ang University’s cultural and artistic programs are considered the best in Korea.
About Associate Professor Tae-Hyung Kim
Tae-Hyung Kim is an associate professor at the School of Integrative Engineering at Chung-Ang University in Korea. He earned his bachelor’s degree in chemical engineering and his doctorate. in Chemical and Biomolecular Engineering from Sogang University, Korea. He was a postdoctoral researcher in the Department of Chemistry and Chemical Biology at Rutgers University, USA. His study focuses on the non-destructive and non-invasive regulation and monitoring of cellular processes using different nanomaterials. He has over 90 peer-reviewed publications to his credit. He sits on the editorial boards of several international journals, including as editor-in-chief of Nano Convergence and associate editor of BioChip Journal.