Researchers use biomolecule-loaded metal-organic frameworks nanopatterns to aid artificial stem cell differentiation
Stem cells are essentially the raw materials of our body – cells that give rise to all other cells and tissues with specialized functions. The 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 injuries and cell damage in our body.
However, things are easier said than done. Conducting stem cell differentiation in the laboratory requires painstaking preparation and addition of differentiation factors into a 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 enables a stable supply of differentiation factors over a long period of time is highly desirable.
In a new study, researchers from Korea, led by associate professor Tae-Hyung Kim of the school of integrative engineering at Chung-Ang University, came up with an ingenious solution. They developed a new platform based on metal-organic frameworks (MOFs), hybrid crystalline porous materials constructed with metal ions and organic ligands (ions/molecules attached to the metal ion). Due to their porous nature, MOFs are excellent for 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 biocompatible nanoparticles needed for stem cell differentiation. This article was published in scientific progress†
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, in the nanocrystalline MOF, nUiO-67. However, there was one problem that had to be taken into account. “Adding nanoparticles directly to the cell culture medium can cause safety concerns when used for therapeutic purposes and can also cause damage to the nanoparticle structures due to the presence of redox enzymes and reactive oxygen species (ROS) in the intracellular environment,” explains Dr. Kim.
To work around this problem, the team separated the stem cells from MOFs by creating a periodic pattern of nanopit arrays using a technique called “laser interference lithography.”
By optimizing these nanopit arrays so that each array captured a single MOF, the team came up with a platform called “single metal-organic framework (MOF) nanoparticle-embedded nanopit arrays (SMENA)” that can automatically convert stem cells into neurons.
SMENA offered two major advantages over the conventional method for in vitro stem cell differentiation. First, it obviates all the complex experimental steps and typical problems related to cell contamination and variation from batch to batch. Second, and surprisingly, the continuous and stable supply of differentiation factors accelerated differentiation, resulting in approximately 40-fold higher expression of neuronal cell markers (indicating the generation of neurons) compared to standard protocols.
These findings have made the team enthusiastic about the future prospects of SMENA. “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 conditions, including the disease of Alzheimer’s and Parkinson’s,” speculates Dr. Kim. The paper was also recently featured as a research highlight in Nature review materials†
Technical researchers develop porous nanoparticles for regenerative medicine
Yeon-Woo Cho et al, Single metal-organic framework-embedded nanopit arrays: a novel way to control neural stem cell differentiation, scientific progress (2022). DOI: 10.1126/sciaadv.abj7736
Provided by Chung Ang University
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