Magnetic Cellular ‘Legos’ For Tissue Engineering

By incorporating magnetic nanoparticles in cells and developing a system using miniaturized magnets, researchers from 3 associated universities* in Paris (France) , have succeeded in creating cellular magneticLegos.” They were able to aggregate cells using only magnets and without an external supporting matrix, with the cells then forming a tissue that can be deformed at will. This approach, which is detailed in Nature Communications, could prove to be a powerful tool for biophysical studies, as well as the regenerative medicine of tomorrow.

Nanotechnology has quickly swept across the medical field by proposing sometimes unprecedented solutions at the furthest limits of current treatments, thereby becoming central to diagnosis and therapy, notably for the regeneration of tissue. A current challenge for regenerative medicine is to create a cohesive and organized cellular assembly without using an external supporting matrix. This is a particularly substantial challenge when it involves synthesizing thick and/or large-sized tissue, or when these tissues must be stimulated like their in vivo counterparts (such as cardiac tissue or cartilage) in order to improve their functionality.

The researchers met this challenge by using magnetism to act on the cells at a distance, in order to assemble, organize, and stimulate them. Cells, which are the building blocks of tissue, are thus magnetized in advance through the incorporation of magnetic nanoparticles, thus becoming true cellular magnetic “Legos” that can be moved and stacked using external magnets. In this new system acting as a magnetic tissue stretcher, the magnetized cells are trapped on a first micromagnet, before a second, mobile magnet traps the aggregate formed by the cells. The movement of the two magnets can stretch or compress the resulting tissue at will.

Researchers first used embryonic stem cells to test their system. They began by showing that the incorporation of nanoparticles had no impact on either the functioning of the stem cell or its capacity for differentiation. These functional magnetic stem cells were then tested in the stretcher, in which they remarkably differentiated toward cardiac cell precursors when stimulation imposed “magnetic beating” imitating the contraction of the heart. These results demonstrate the role that purely mechanical factors can play in cell differentiation.

This “all-in-one” approach, which makes it possible to build and manipulate tissue within the same system, could thus prove to be a powerful tool both for biophysical studies and tissue engineering.

* Laboratoire Matière et Systèmes Complexes (CNRS/Université Paris Diderot), in collaboration with the Laboratoire Adaptation Biologique et Vieillissement (CNRS/UPMC) and the Centre de Recherche Cardiovasculaire de Paris (Inserm/Université Paris Descartes)


How To Repair Nerve Tissue Injuries

Regenerative medicine using stem cells is an increasingly promising approach to treat many types of injury. Transplanted stem cells can differentiate into just about any other kind of cell, including neurons to potentially reconnect a severed spinal cord and repair paralysis.

A variety of agents have been shown to induce transplanted stem cells to differentiate into neurons.  Tufts University biomedical engineers recently published the first report of a promising new way to induce human mesenchymal stem cells (or hMSCs, which are derived from bone marrow) to differentiate into neuron-like cells:  treating them with exosomes.

exosome2Exosomes are very small, hollow particles that are secreted from many types of cells. They contain functional proteins and genetic materials and serve as a vehicle for communication between cells. In the nervous system, exosomes guide the direction of nerve growth, control nerve connection and help regenerate peripheral nerves.

In a series of experiments reported in PLOS ONE in August, the Tufts researchers showed that exosomes from PC12 cells (neuron-like progenitor cells derived from rats) at various stages of their own differentiation could, in turn, cause hMSCs to become neuron-like cells. Exosomes had not previously been studied as a way to induce human stem cell differentiation.

The biomedical engineers also showed that the exosomes contain miRNAs—tiny pieces of RNA that regulate cell behavior and are known to play a role in neuronal differentiation. The researchers hypothesize that the exosomes caused the hMSCs to differentiate by delivering miRNA into the stem cells. The researchers plan future studies to determine the exact mechanism.

“In combination with synthetic nanoparticles that my laboratory is developing, we may ultimately be able to use these identified miRNAs or proteins to make synthetic exosomes, thereby avoiding the need to use any kind of neural progenitor cell line to induce neuron growth,” said the paper’s senior and corresponding author Qiaobing Xu, assistant professor of biomedical engineering at Tufts School of Engineering.


Nanotechnology To Heal Pets

Modern medicine is evolving quickly. Now, with the introduction of bioengineering, doctors can have tissue made for their patients and veterinarians are having great success using nanotechnology in our pets.
Dr. Jed Johnson has a PhD in engineering and his firm engineers body tissue. He explains: “The part that I focus on is tissue engineering, where we are basically focusing and building or engineering new tissue for the body.”
Their nanotechnology is an integral part of regenerative medicine.
We’ve all seen regeneration. We’ve all had cuts on our hands, right? And those cuts heal. So, our body is capable of healing, but we have to provide the right environment,” , said the Dr. Hutchinson, from Animal General in Cranberry.
Enter nanofibers.
It takes a hundred of the microscopic fibers laid side-by-side to be as wide as a human hair.
Weave them together, and they provide a framework for healing.
Cells and tissue can’t move across open space, they have to crawl on something, and this is really the key aspect to having a scaffold is it allows those cells to have a highway to move on to refill that wound, regenerate that native tissue,” Dr. Johnson said.
You can’t do that synthetically. I mean, we can’t do that without the help of what someone like Dr. Johnson’s doing with nanofibers,” Dr. Mike Hutchinson said.
Dr. Hutchinson uses nanofibers in combination with stem cells to speed up the healing.
They will do a lot of good for as long as they stay, but we would like to keep them there longer in that damaged environment. So, they have made some nanowhiskers, if you will, that we mix with the stem cells before we inject them in, and they will hold them there. They will give them something to grow on or to hug to and keep them there longer,” Dr. Hutchinson said.


How To Close Deep Wounds In A Few Seconds

A significant breakthrough could revolutionize surgical practice and regenerative medicine. A team led by Ludwik Leibler from the Laboratoire Matière Molle et Chimie (CNRS/ESPCI Paris Tech) and Didier Letourneur from the Laboratoire Recherche Vasculaire Translationnelle (INSERM/Université Paris Diderot and Université Paris 13) – France -, has just demonstrated that the principle of adhesion by aqueous solutions of nanoparticles can be used in vivo to repair soft-tissue organs and tissues.

This easy-to-use gluing method has been tested on rats. When applied to skin, it closes deep wounds in a few seconds and provides aesthetic, high quality healing. It has also been shown to successfully repair organs that are difficult to suture, such as the liver. Finally, this solution has made it possible to attach a medical device to a beating heart, demonstrating the method’s potential for delivering drugs and strengthening tissues.
This work has been published on the website of the journal Angewandte Chemie.

Nano-hitchhikers Track Stem Cells Entering Heart

The promise of repairing damaged hearts through regenerative medicine — infusing stem cells into the heart in the hope that these cells will replace worn out or damaged tissue — has yet to meet with clinical success. But a highly sensitive visualization technique developed by Stanford University School of Medicine scientists may help speed that promise’s realization.

All stem cell researchers want to get the cells to the target site, but up until now they’ve had to shoot blindly,” said Gambhir, who is also the Virginia and D.K. Ludwig Professor in Cancer Research and director of the Molecular Imaging Program at Stanford. “With this new technology, they wouldn’t have to. For the first time, they would be able to observe in real time exactly where the stem cells they’ve injected are going and monitor them afterward. If you inject stem cells into a person and don’t see improvement, this technique could help you figure out why and tweak your approach to make the therapy better.”