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Self-organ regeneration

Heart renewal in newts

01.02.2018
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When newts lose a leg, they regenerate a new one.  Even destroyed cardiac tissue is swiftly replaced by healthy tissue. What is the underlying mechanism?

Dr. Klaus Duffner | Germany

Newts and salamanders have the unique attribute to fully regenerate lost limbs. Not only lost legs, also eye lenses, the jaw, parts of the central nervous system and even cardiac tissue are fully restored.

Scientists at the Max-Planck Institute for Cardiac and Pulmonary Research in Bad Nauheim, Germany, have been working intensively for years on the mechanisms underlying this phenomenal regenerative capacity.

Cell movements after a heart attack

In their experiments the researchers chiefly focused on the approximately ten centimeter in length eastern newt, one of the most common species in North America.

To begin with, its heart was subjected to mechanical damage in an operation and the result can be compared to the situation after a myocardial infarction in humans.

But after just a few days, microscopic observation reveals how countless inflammatory cells (chiefly leukocytes) migrate to the damaged area and eliminate the cell debris. Thread-like structures then form from individual heart muscle cells, after which within the space of a few months more and more cells then colonize these so-called trabeculae until finally - supported by a collagenous protein scaffold – the heart muscle is completely regenerated.


Research in full swing

Scientists throughout the world are currently working on methods for tissue-engineering human organs using 3D printers. Most models, however, are still on the drawing board. In particular, building functional organs that rely on nutrient blood vessels and nerves is still a pipe dream in the view of researchers like Simon Hoerstrup, the Director of the Institute for Regenerative Medicine at the University of Zurich, where polymer scaffolds are subsequently coated with the patients’ own cells using a 3D printer.4 In children with serious congenital heart defects, Dr. Hoerstrup intends to implant living, i.e., growing, heart valves after birth. What he has already shown can work in animal experiments on lambs is soon to be studied in the clinic with human babies. The development of less complex tissues like heart valves, blood vessels and cartilage that do not need a direct supply of blood nutrient is already well ahead. For example, Swedish researchers recently made cartilage consisting of a new hydrogel biomaterial and human cells, which grew successfully in mouse skin.5

Meanwhile, a team of researchers at the University of California in San Diego (UCSD) was successful using a 3D printer to manufacture a small, functional system of blood vessels and implant it into live mice.6 And a new hydrogel made from alginate, polyvinyl alcohol and hydroxyapatite was recently developed by scientists led by Stephanie T. Bendtsen at the Institute for Material Sciences, University of Connecticut. The alginate is designed to improve the properties of bones “printed” using 3D printers.7 Finally, victims of serious burns and animal testing for cosmetics and drugs could benefit from a bilayer human skin sourced from a 3D printer. A bio-ink for the printer cartridges containing blood plasma, fibroblasts and keratinocytes was developed by Spanish scientists, and the resulting bilayer skin grew without difficulty when implanted in mice.


New ears

Using an experimental technique at the end of last year, Chinese researchers created a new ear by an unusual means.9 The patient lost an ear that had been damaged irreparably in a car accident. Dr. Wang Jihua, Director of Plastic Surgery at the Kunming Medical Second Hospital, printed a model of an ear using a 3D printer and fashioned a new ear out of rib cartilage. This model was then implanted under the skin of the patient’s arm, so it could continue to grow for subsequent transplant onto the patient’s head. Doctors are also currently using 3D printing techniques in Edinburgh, Scotland to make a new ear for a nine year old girl afflicted by a congenital ear muscle abnormality. Using a 3D printer, researchers created a mirror image of the normal ear out of plastic and used this template to model a new ear from rib cartilage. Initial surgery entailed the plastic ear being attached to the head beneath the skin in order to create the site and structure for the new ear. As soon as the skin has adapted, a second operation will allow the replacement ear to be attached in the desired position.

Be it ears, heart valves, skin, bone, kidneys or other tissues: 3D technology could soon open up a new era in medicine.

Dr. Klaus Duffner

Dr. Klaus Duffner | Germany

Scientific Journalist
Medizin & Wissen Freiburg

Sources
  1. Kubin T, et al.: Cell Stem Cell 2011; 9 (5): 420–32.
  2. Szibor M, et al.: Cell Mol Life Sci 2014; 71(10): 1907–16.
  3. Reinberger S: Max Plank Forschung 2014; 2: 52–57.
  4. Heil M, Braun T: Forschung Frankfurt 2013; 1: 53–57.
  5. Neubauer U: Hessen-Biotech; 2013; 3: 10–11.
  6. Reinberger S: MPI-Video. 2016. (http://www.sciviews.de/video/vom-molch-lernen)

 Photo Header: MPI for Cardiac and Pulmonary Research

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