SCIENTISTS GENERATE FIRST HUMAN TISSUE IN L AB WITH STEM CELLS

Scientists used pluripotent stem cells to generate functional, three-dimensional human stomach tissue in a laboratory -- creating an unprecedented tool for researching the development and diseases of an organ central to several public health crises, ranging from cancer to diabetes.

Scientists at Cincinnati Children's Hospital Medical Center report Oct. 29 in Nature they used human pluripotent stem cells -- which can become any cell type in the body -- to grow a miniature version of the stomach. In collaboration with researchers at the University of Cincinnati College of Medicine, they used laboratory generated mini-stomachs (called gastric organoids) to study infection by H. pylori bacteria, a major cause of peptic ulcer disease and stomach cancer.

This first-time molecular generation of 3D human gastric organoids (hGOs) presents new opportunities for drug discovery, modeling early stages of stomach cancer and studying some of the underpinnings of obesity related diabetes, according to Jim Wells, PhD, principal investigator and a scientist in the divisions of Developmental Biology and Endocrinology at Cincinnati Children's.

It also is the first time researchers have produced 3D human embryonic foregut -- a promising starting point for generating other foregut organ tissues like the lungs and pancreas, he said.

"Until this study, no one had generated gastric cells from human pluripotent stem cells (hPSCs)," Wells said. "In addition, we discovered how to promote formation of three-dimensional gastric tissue with complex architecture and cellular composition."

This is important because differences between species in the embryonic development and architecture of the adult stomach make mouse models less than optimal for studying human stomach development and disease, Wells added.

Researchers can use human gastric organoids as a new discovery tool to help unlock other secrets of the stomach, such as identifying biochemical processes in the gut that allow gastric-bypass patients to become diabetes-free soon after surgery before losing significant weight. Obesity fueled diabetes and metabolic syndrome are an exploding public health epidemic. Until now, a major challenge to addressing these and other medical conditions involving the stomach has been a relative lack of reliable laboratory modeling systems to accurately simulate human biology, Wells explained.

The key to growing human gastric organoids was to identify the steps involved in normal stomach formation during embryonic development. By manipulating these normal processes in a petri dish, the scientists were able to coax pluripotent stem cells toward becoming stomach. Over the course of a month, these steps resulted in the formation of 3D human gastric organoids that were about 3mm (1/10th of an inch) in diameter. Wells and his colleagues also used this approach to identify what drives normal stomach formation in humans with the goal of understanding what goes wrong when the stomach does not form correctly.

Along with study first author Kyle McCracken, an MD/PhD graduate student working in Wells' laboratory, and Yana Zavros, PhD, a researcher at UC's Department of Molecular and Cellular Physiology, the authors report they were impressed by how rapidly H. pylori bacteria infected stomach epithelial tissues.

Within 24 hours, the bacteria had triggered biochemical changes to the organ, according to McCracken. The human gastric organoids faithfully mimicked the early stages of gastric disease caused by the bacteria, including the activation of a cancer gene called c-Met and the rapid spread of infection in epithelial tissues.

Another significant part of the team's challenge has been the relative lack of previous research literature on how the human stomach develops, the authors said. Wells said the scientists had to use a combination of published work, as well as studies from his own lab, to answer a number of basic developmental questions about how the stomach forms. Over the course of two years, this approach of experimenting with different factors to drive the formation of the stomach eventually resulted in the formation of 3D human gastric tissues in the petri dish.

Wells emphasized importance of basic research for the eventual success of this project, adding, "This milestone would not have been possible if it hadn't been for previous studies from many other basic researchers on understanding embryonic organ development."

Nerve Damage Repair By Tissue Engineering

Today's post from sciencedaily.com (see link below) is an interesting look at the research showing that by using Schwann cells as the basis (cells that wrap themselves around the nerve and form the protective sheath myelin), nerves can be regenerated. At the moment, a nerve transplant is necessary but is often unsuccessful. Moreover, this can only have a chance of success if the transplant takes place very soon after the initial injury. People with long-term nerve damage have a very small chance of nerve regeneration via transplantation. The new research opens up possibilities of using Schwann cells to regenerate and elongate damaged nerves, so that they better fuse with healthy axons further away. It's a form of tissue engineering with fascinating possibilities for the future.

New Tissue Engineering Breakthrough Encourages Nerve Repair
July 8, 2013 Science News
... from universities, journals, and other research organizations

A new combination of tissue engineering techniques could reduce the need for nerve grafts, according to new research by The Open University. Regeneration of nerves is challenging when the damaged area is extensive, and surgeons currently have to take a nerve graft from elsewhere in the body, leaving a second site of damage. Nerve grafts contain aligned tissue structures and Schwann cells that support and guide neuron growth through the damaged area, encouraging function to be restored.

The research, published in Biomaterials, reported a way to manufacture artificial nerve tissue with the potential to be used as an alternative to nerve grafts.

Pieces of Engineered Neural Tissue (EngNT) are formed by controlling natural Schwann cell behaviour in a three-dimensional collagen gel so that the cells elongate and align, then a stabilisation process removes excess fluid to leave robust artificial tissues. These living biomaterials contain aligned Schwann cells in an aligned collagen environment, recreating key features of normal nerve tissue.

Incorrect orientation of regenerating nerve cells can lead to delays in repair, scarring and poor restoration of nerve function. Much research has taken place into how support cells (Schwann cells) can be combined with materials to guide nerve regeneration. The new technology from The Open University avoids the use of synthetic materials by building neural tissue from collagen, a protein that is abundant in normal nerve tissue. Building the artificial tissue from natural proteins and directing the cellular alignment using normal cell-material interactions means the EngNT can integrate effectively at the repair site.

Dr James Phillips, Lecturer in Health Sciences at The Open University, said: "We previously reported how self-alignment of Schwann cells could be achieved by using a tethered collagen hydrogel, which exploited cells' natural ability to orientate in the appropriate direction by using their internal contraction forces. Our current research shows that cell-alignment in the hydrogel can be stabilised using plastic compression. The compression removes fluid from the gels, leaving a strong and stable aligned structure that has many features in common with nerve tissue."

The team incorporated Schwann cells within the aligned material to form artificial neural tissue that could potentially be used in peripheral nerve repair. The technique could be applied to other regenerative medicine scenarios, where a stable artificial tissue containing aligned cellular architecture would be of benefit.

http://www.sciencedaily.com/releases/2013/07/130708102938.htm

Tissue Biopsies to Prove Neuropathy

Elsewhere on the blog, are posts about the most common test for neuropathy: the Electromyography or EMG but that's not the only test that can be done to establish whether Neuropathy is the cause of your complaints. Today's post from The Foundation for Peripheral Neuropathy,(see link below) concerns something else you may have seen mentioned in this regard: the Nerve / Skin / Muscle / Tissue Biopsy. As you probably know, a biopsy is the taking of a small piece of tissue from a certain area, for microscopic investigation in a lab elsewhere. We normally hear of it in suspected cancer cases. It's not usually carried out for neuropathy unless close investigation of small nerve damage is deemed necessary by your doctor. If this happens to be one of your options, this short article explains clearly and concisely what's involved.

Nerve / Skin / Muscle / Tissue Biopsy

Biopsies are small samples of nerves, skin, muscle or other tissues that are removed from the body. The samples are examined to identify and diagnose various disorders.

What is it?

A biopsy is a minor surgical procedure which involves making a small incision to remove a sample of nerve, skin, muscle or tissue for examination.

Why should I do it?

A nerve biopsy may help distinguish between demyelination (damage to the myelin sheath covering the nerve) and axon degeneration (destruction of the axonal portion of the nerve cell). It may also help identify an inflammatory neuropathy or confirm specific diagnoses.

A nerve biopsy is invasive and is useful only in certain circumstances.

A skin biopsy is helpful to distinguish certain disorders that might affect the small nerve fibers, as may be the case with painful sensory axonal neuropathies.

A muscle or other tissue biopsy is used to diagnose and identify damage caused to muscles and organs as a result of various disorders such as Charcot-Marie-Tooth disease, sarcoidosis and amyloidosis.

How is a nerve biopsy performed?

A nerve, skin, muscle or other tissue biopsy usually is a simple outpatient procedure. For a nerve biopsy, a local anesthetic is used to numb the area. The surgeon makes a small incision and removes a portion of the nerve, usually from the ankle or the calf. The sample is then examined for abnormalities under a microscope.

A skin, muscle or other tissue biopsy is performed much the same way, except that the surgeon removes skin, muscle, or other tissue instead of nerve.

How will it feel?

Because a local anesthetic is used, discomfort during the procedure is usually minimal. The anesthetic may burn or sting when first injected. After the procedure, the area may feel tender or sore for a few days. An area of the skin may remain permanently numb after the biopsy.

http://www.foundationforpn.org/livingwithperipheralneuropathy/evaluation/neurologicaltests/index.cfm