Medical Device Daily National Editor

Tissue engineering has long been considered a pathway to new therapeutic advances, and these strategies are coming in diverse array.

Three examples recently reported:

Using stem cell lines not typically associated with each other, researchers at Columbia University Medical Center (New York) have designed a new way to "grow" bone and other tissues by using two lines in a combination strategy.

The researchers say that the significance of the research is in this combined strategy, not pursued before because the two tissue lines tend to reside in different silos of research interest.

A team of researchers at Columbia University Medical School co-transplanted hematopoietic and mesenchymal stem/progenitor cells in a way that promoted the regeneration of vascularized tissues. What they found was that the tissue regenerated in bone grew more rapidly than when either type of stem cell was used alone.

The work, by Jeremy Mao, DDS, PhD, published in the Public Libraries of Science, involved the seeding of human mesenchymal stem/progenitor cells multipotent cells that can differentiate into various others cell types into micropores of 3-D calcium phosphate scaffolds. This was followed by the infusion of gel-suspended CD34+ hematopoietic cells which have the ability to grow into blood cells.

Mao and his team observed greater vascularization in the mice than when mesenchymal cells were used alone. Additionally, they found that the number of vessels and the diameter of the vessels produced by the co-transplantation of the two cell types was "dramatically" increased when combined with Vascular Endothelial Growth Factor (VEGF).

The researchers said this improved over previous attempts to grow new blood vessels, due to the difficulties in fostering angiogenesis. These previous approaches have included the use of angiogenic growth factors and the fabrication of artificial blood vessels. Artificially fabricated blood vessels do not readily branch out and network with host blood vessels, and blood vessels induced by angiogenic growth factors are immature and tend to be "leaky."

The goal of the research, then, was to solve these problems.

Mao said, "The work has potential beyond bones and may have implications for the growth of muscle, nerve and organs. The synergistic action of mesenchymal cells and hematopoietic cells provide an alternative approach for regrowing a host of vascular tissues."

Ira Lamster, MD, dean of the Columbia University College of Dental Medicine, praised the research approach because representing "the fruits of interdisciplinary science." Mao's work, he said, "has relevance for oral healthcare, as well as many other health care disciplines."

• Researchers at the University of Pennsylvania School of Medicine (Philadelphia) have reported the discovery of stem cells in the esophagus of mice that were then able to grow into tissue-like structures. When placed into immune-deficient mice, the tissue structures were able to form parts of an esophagus lining.

The research is reported in the online edition of the Journal of Clinical Investigation.

Senior study author Anil Rustgi, MD, the T. Grier Miller Professor of Medicine and Genetics and chief of gastroenterology, said the main implication of the study is "a better understanding of the role of these stem cells in normal biology, as well as in regenerative and cancer biology. Down the road, we will develop a panel of markers that will define these stem cells and use them in replacement therapy for diseases like gastroesophogeal reflux disease [GERD] and also to understand Barrett's esophagus," this latter considered a precursor to esophageal cancer.

The researchers set out to identify and characterize potential stem cells in the esophagus to understand normal biology and how injured cells may one day be repaired.

First, they grew mouse esophageal cells they suspected were adult stem cells. Those cells formed colonies that self renewed and then grew into esophageal lining tissue in a 3-D culture apparatus.

"These tissue culture cells formed a mature epithelium sitting on top of the matrix," said Rustgi, calling this construct "a form of tissue engineering."

The investigators then tested their pieces of esophageal lining in whole animals. When the tissue-engineered patches were transplanted under the skin of immunodeficient mice, the cells formed epithelial structures. Additionally, in a mouse model of injury of the esophagus in a normal mouse, green-stained stem cells migrated to the injured lining cells and co-labeled with the repaired cells, indicating involvement of the stem cells in tissue repair and regeneration.

The researchers said they will develop genetically engineered mouse models to be able to track molecular markers of esophageal stem cells found in a micorarray study. They have already developed a library of human esophageal cell lines and is looking for human versions of markers already identified in mice.

"The ultimate goal is to identify esophageal stem cells in a patient, grow the patient's own stem cells, and inject them locally to replace diseased tissue with normal lining," said Rustgi.

This work was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute.

• In another cell technology effort, scientists at the University of New South Wales (Sydney, Australia) reported the use of nose cells from humans in a way that may lead to the treatment of some forms of paralysis.

In a study presented last month at the annual conference of the Society of Neuroscience (Washington), the researchers described how they injected paralyzed rats with human nose cells. Six weeks later, the rats could move their hind legs.

The researchers said they are hopeful this technique might eventually be used for treatment of humans.

While connection to a neurological applications derives from the fact that the nose cells, called olfactory ensheathing glia cells, normally help to regrow the fibers that link the lining of the nose to the brain.

Catherine Gorrie, MD, of the University of New South Wales, led the study and called these types of cells "very accessible. It's a relatively simple procedure to take them from the patient, grow more of them in the laboratory and then insert them back into the same person."