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)


Artificial Embryo From Stem Cells

Scientists at the University of Cambridge have managed to create a structure resembling a mouse embryo in culture, using two types of stem cells – the body’s ‘master cells’ – and a 3D scaffold on which they can grow. Understanding the very early stages of embryo development is of interest because this knowledge may help explain why a significant number of human pregnancies fail at this time.

Once a mammalian egg has been fertilised by a sperm, it divides multiple times to generate a small, free-floating ball of stem cells. The particular stem cells that will eventually make the future body, the embryonic stem cells (ESCs) cluster together inside the embryo towards one end: this stage of development is known as the blastocyst. The other two types of stem cell in the blastocyst are the extra-embryonic trophoblast stem cells (TSCs), which will form the placenta, and primitive endoderm stem cells that will form the so-called yolk sac, ensuring that the foetus’s organs develop properly and providing essential nutrients.

Using a combination of genetically-modified mouse ESCs and TSCs, together with a 3D scaffold known as an extracellular matrix, Cambridge researchers were able to grow a structure capable of assembling itself and whose development and architecture very closely resembled the natural embryo.  There is a  remarkable degree of communication between the two types of stem cell: in a sense, the cells are telling each other where in the embryo to place themselves.

artificial embryo

We knew that interactions between the different types of stem cell are important for development, but the striking thing that our new work illustrates is that this is a real partnership – these cells truly guide each other,”  says Professor Zernicka-Goetz. “Without this partnership, the correct development of shape and form and the timely activity of key biological mechanisms doesn’t take place properly.”

Comparing their artificial ‘embryo’ to a normally-developing embryo, the team was able to show that its development followed the same pattern of development. The stem cells organise themselves, with ESCs at one end and TSCs at the other.

The study has been published in the journal Science.


Blindness Cure From Stem Cells

The first patient has been treated in Britain in a pioneering trial of a new treatment co-developed by Pfizer and derived from embryonic stem cells designed for patients with a condition that can cause blindness. Specialists at London’s Moorfields Eye Hospital said the operation, described as “successful”, was the first of 10 planned for participants in a trial of the treatment for a disease called ‘wetage-related macular degeneration (AMD). The trial will test the safety and efficacy of transplanting eye cells known as retinal pigment epithelium, which have been derived from embryonic stem cells.

eye2Stem cells are the body’s master cells, the source of all other cells. Scientists who support the use of embryonic stem cells say they could transform medicine, providing treatments for blindness, juvenile diabetes or severe injuries. But critics object to them because they are harvested from human embryos.

This trial involves surgeons inserting a specially engineered patch behind the retina to deliver the treatment cells to replace diseased cells at the back of the eye. The first surgery was successfully performed on a patient last month, Moorfields said in a statement on Tuesday, and “there have been no complications to date“.

The patient wishes to remain anonymous, but the team hope to determine her outcome in terms of initial visual recovery by early December,” it added.

Retinal surgeon Lyndon Da Cruz, who is performing the operations, said he hoped many patients “will benefit in the future from transplantation of these cells.”

Macular degeneration accounts for almost 50 percent of all cases of blindness or vision loss in the developed world. It usually affects people over 50 and comes in two forms, wet and dry. Wet AMD, which is less common than dry AMD, is generally caused by abnormal blood vessels that leak fluid or blood into a region in center of the retina.