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29 January 2016

Tissues from the Lab

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Making human organs and tissues in the laboratory that work identically to the originals is not some fantasy from the creator of Frankenstein. In fact, an artificial contractile muscle and some human vocal cords developed by bioengineers entirely in the laboratory were selected as being among the ten major scientific breakthroughs of 2015. Although the first clinical applications will take a few years to become a reality, scientists are just about ready with the technology necessary to develop replacement healthy tissues with which to repair virtually any diseased organ of the body. Here we review the latest achievements of the new regenerative medicine.

Stomach

Just a handful of human stem cells were enough for researchers at the Cincinnati Children’s Hospital Medical Center (USA) in 2014 to create a miniature version of a stomach. “We have discovered how to promote the formation of three-dimensional gastric tissue with a complex composition and cellular structure,” said Jim Wells, an expert in Developmental Biology and Endocrinology and coauthor of the study. The key is to be able to replicate in Petri dishes the exact steps in the formation of the stomach during embryonic development, which has been used as an instruction book.

This “laboratory gut” could also be replicated in the future in a life-sized version and be transplanted, for example, into patients with gastric cancer. In addition, mini-stomachs made by these bioengineers are suitable for investigating in detail how the infection caused by the bacteria Helicobacter pylori, which is responsible for peptic ulcers, evolves in real time, or analyzing how obesity affects the operation of this organ, among other possible applications.

Vocal chords

In November 2015, scientists from the University of Wisconsin-Madison (USA) announced a major achievement: human vocal cord tissue had been made in the laboratory which could help restore the voices of the millions of people who have this part of the

Credits: Kyle McCracken

ir body damaged as a result of cancer or other diseases. It has not been easy. “Our vocal cords are made of a special material that must be, on the one hand, flexible enough to vibrate as air passes through and, on the other hand, strong enough to withstand hundreds of oscillations per second without breaking,” says Nathan Welham, co-author of the study. “It’s a sophisticated and difficult to replicate system,” he admits. Welham and his team isolated vocal cord cells from a corpse and made them grow on a 3D collagen frame. In two weeks, the cells formed a structure of vocal cords that vibrated in an identical way to the original.

Credits: ENT department, Medical College of Georgia

Ovaries and vagina

Hormonal problems suffered by women who have had an ovary removed, who are affected by cancer or who are beginning menopause may be a thing of the past thanks to the ovaries created by artificial engineering at the Institute for Regenerative Medicine at Wake Forest Medical Center. “A bio-artificial ovary that naturally releases sex hormones like estrogen and progesterone is better than supplying these types of hormones artificially,” explained Emmanuel C. Opara, head of the research.

On the premises of this same institute, expert Anthony Atala and his team transplanted, for the first time, into four adolescents, vaginal tissue grown in the laboratory from their own cells, previously extracted in a biopsy. The cells were made to grow in a biodegradable material in the shape of a vagina tailored to each patient, which surgeons implanted after 6 weeks growing in Petri dishes. Once implemented, the cells began to form around the tissue and, spontaneously, new nerves and blood vessels appeared, and the new organ was integrated with the other reproductive organs.

Credits: Wake Forest Baptist Medical Center

Muscle

Would it be possible to manufacture, using pipettes and Petri dishes, a muscle that contracts and responds to electrical impulses just like the tissue of your biceps and triceps? Scientists from Duke University (USA) have proven this to be possible. The process used was to take a handful of human cells that were no longer stem cells but also that had not yet become muscle (myogenic precursors) and growing them a thousand-fold on special polymer frames filled with gel that allowed the tissue to align and function as muscle fibers. For now, this laboratory muscle will be used to test new drugs and observe how human muscle tissue reacts in real time. Researchers hope that this technique will form the basis of new personalized treatments, starting with a biopsy from each patient with muscle diseases, growing new muscles in the laboratory and experimenting until the medication that works best for each person is found.

Credits: Nenad Bursac, Duke University

Blood vessels

There is no healthy organ without good blood flow. Therefore, manufacturing quality blood vessels in the laboratory has become one of the goals of regenerative medicine. Scientists at Rice University in 2011 took a decisive step forward using polyethylene glycol, a non-toxic plastic that can mimic the body’s extracellular matrix, i.e. the network of proteins and sugars that supports most tissues. They combined it with two types of cells necessary for the formation of vessels, successfully creating networks of fine capillaries. And last year, at the Vienna University of Technology, researchers developed another alternative to create synthetic blood vessels from liquid, biodegradable and porous polymers that, once implanted, are replaced by the body’s own tissues, resulting in a natural blood vessel that is healthy and fully active.

Credits: Brigham and Women’s Hospital

Heart

The credit for creating the first artificial heart that can beat in a laboratory goes to the Center for Cardiovascular Repair at the University of Minnesota (USA). In 2008, its researchers used a process called whole cell decellularization to make functional heart tissue from the hearts of dead rodents and pigs in order to “reseed” them with living cells. Four days after incorporating the cells, contractions were observed in some areas, and after eight days the hearts were beating.

Credits: Thomas Matthiesen, University of Minnesota

Neurons

Studying how the complex web of neural connections in our brains works will be easier thanks to the 3D model of a cerebral cortex created two years ago by Tufts University (USA), replicating the cerebral cortex of a rat. Although this is not a complete brain, the artificial replica is quite complete because it contains gray matter (the cell bodies of neurons) and white matter (the axons of neurons). The neurons, in this case of a rat, are arranged in concentric rings simulating the formation of layers in the brain. The 3D model, which can survive for more than two months, will be useful for studying brain functioning in real time, as well as the effects of drugs on neurons and the diseases that affect them, according to the authors in the journal PNAS.

Credits: Tufts University

By Elena Sanz for Ventana al Conocimiento (Knowledge Window)
@ElenaSanz_

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