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The goal of regenerative medicine is to fully repair damaged tissues and organs through several means. These include promoting natural healing processes, replacing the damaged cells, tissues or organs with healthy ones, or integrate specific types of cells, such as stem cells, into the diseased tissues or organs to allow for regeneration of the lost function.
Through a process known as cell differentiation, stem cells are able to transform into any type of cell within the body, depending upon the stimulus that it takes. Stem cells, which can be acquired from both adult and embryonic sources, therefore play a key role in progressing regenerative medicine as a result of their capability to completely repair itself and any affected areas of interest1.
To combat some of the challenges that Researchers face in their strategies to induce cell differentiation for regenerative medical purposes, a team of Researchers from the Laboratoire Matière et Systèmes Complexes (CNRS/Université Paris Diderot) have created a Lego-like magnetic structure to induce stem cell aggregation and tissue formation.
In their approach, the French Researchers began by incubating magnetic nanoparticles within embryonic stem cell (ESC) cultures for time durations of 30 minutes, 2 hours and 4 hours, with 30 minutes at a concentration of 2 millimolar (mM) of magnetic nanoparticles being the safest option, as it was not shown to negatively affect cell viability.
Pluripotency, which describes the ability of stem cells to successfully differentiate in different types of specific organs or tissues, was tested in the magnetic nanoparticle cell cultures, or magnetized ESCs by comparing the cellular morphology to undifferentiated stem cells which typically show a regular and rounded shape. The attraction of the magnetic nanoparticles within the magnetized ESCs allows for the cells to come together, thereby forming a mass.
To test the magnetic potential of the magnetized ESCs, the Researchers applied and tracked the cellular mobility by placing a magnetic device beneath the incubated cells, which exposed the ESCs to several magnetic attractors. The application of this external magnet was applied at various different time points ranging from 5 minutes to two days, a process which initiated the cellular differentiation of the magnetized ESCs.
The magnetic formation of stem cell-derived structures was compared to the hanging drop method, which measures the motility of cellular species. In comparison to this procedure, the magnetic formation demonstrated in this study allows for a much more regulated approach to embryonic formation, while simultaneously eliminating the high variability in shape and size that is seen following application of the hang drop method.
The Researchers finally applied a magnetic stretcher in order to fully form and stimulate the complete growth and differentiation of the embryonic tissue. Once magnetized by the magnetic microtips originally applied to the cell culture, these embryonic masses can then be stretched and/or stimulated by the application of a magnetic stretcher.
The magnetic forces of this stretcher act as a clamp to stretch the intermediate parts of the embryonic tissue and exert pulling forces to create a 3D aggregate structure that can be further manipulated with the application of other magnetic forces.
To test the ability of the magnetized ESCs to differentiate into a specific organ’s tissue of interest, the Researchers looked at the genetic expression of the magnetized ESCs. Genetic studies confirmed that the magnetized ESCs displayed an increase in the expression of Gata4, Gata6, Sox17 and Nkx2.52. As all of these genes play an important role in the differentiation of cardiac mesoderm cells, the Researchers applied the magnetic stretcher to specifically enhance differentiation of the magnetized ESCs towards a cardiac phenotype.
The proposed technology in this study offers a unique approach to regenerative medicine, and further studies in in vivo models must be conducted to test the validity of this model. Toxicity studies are also necessary before this concept can be applied to possible clinical trial settings, as the presence of magnetic nanoparticles can be harmful in the organism, despite the promising cellular data found in this study.
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References:
- “About Regenerative Medicine” – Mayo Clinic
- “A 3D magnetic tissue stretcher for remote mechanical control of embryonic stem cell differentiation” V. Du, N. Luciani, et al. Nature Communications. (2017). DOI: 10.1038/s41467-017-00543-2.
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