Scientists regrow damaged tissue

With advancements in regenerative medicine and more aggressive experimentation, stem cell research has now enabled people to do what only starfish could do until now: regrow parts of their bodies that have been damaged or amputated.

Although in the early stages of development, stem cell regenerative growth can successfully help regrow damaged parts of a person’s body. A team lead by Stephen Badylak, professor of surgery at the University of Pittsburgh’s McGowan Institute for Regenerative Medicine, has used this stem cell method to generate actual tissue growth instead of just scar tissue, which is fibrous tissue normally formed after an injury and is inferior to healthy tissue. Such growth does not occur in humans naturally, except during the developmental stages of gestation.

Badylak’s approach begins with the use of an extracellular matrix (ECM). The purpose of the matrix is to provide structural support to the cells it surrounds, and help regulate cellular communication. This matrix includes the material that resides between the cells in tissues and organs and is composed of structural materials and signaling molecules. Scientists are able to harvest such extracellular matrices by taking cells from the bladder and removing all of the cells, so that all that is left is the matrix.

“We hypothesize that the signaling molecules within the matrix are important in the constructive remodeling process,” Badylak said. These matrices, also called scaffolds, contain all of the molecules that seem to help the process of tissue regeneration. When the matrix gets implanted into damaged or missing tissue, the host, or the recipient of the scaffold material degrades it to these signaling molecules. These molecules in turn signal other cells to come to the site and help the process of tissue regrowth.

According to Badylak, this type of tissue regeneration has already been used in thousands of patients as treatment for various conditions. In fact, as reported in the Pittsburgh Tribune-Review, Badylak managed to induce seven millimeter growth in the amputated index finger of Army Staff Sgt. Shilo Harris. The article further states that Harris was the first soldier to undergo such an experimental procedure. The method made use of a powder derived from the extracellular matrix of cells from a pig’s bladder. Although the growth was not substantial, it was a start in the right direction. In the Tribune-Review, Harris was quoted saying, “If we gain anything, that’s something.”

As for regrowing whole limbs, Badylak is unsure of when technology will be advanced enough for such a feat. “That’s an impossible question really to answer. I do think that we will be able to stimulate the regrowth of at least digits,” he said. “The only way we will be able to do that is by understanding the signaling mechanisms that occur in the fetus, when these sorts of structures are normally developed. In a fetus if you amputate these structures at an early enough stage, the fetus will regrow a limb. Yet we lose that ability as we develop into a newborn.”

The hardest obstacle of regenerative medicine lies within the cellular communication system. Badylak explained that to regrow a tissue, the cell requires the right kind of signal to start, so that it can in turn stimulate the right cells. The biggest challenge is finding the master switch, a molecular signal which will tell the injured tissue to respond with the means to regrow instead of just heal, and afterward, finding out how activate it. These switches are genes that need to be activated. When activated, the genes can then express proteins that can trigger a cell regeneration cascade.

In order to find such genes, Badylak has been comparing the gene expression patterns of salamanders and other species, which have regenerative growth DNA, to those of mammals. His goal is to find similar gene sequences that are turned on in salamanders but not in mammals, and to find key differences between the two patterns. “By finding those particular patterns, we may be able to pick out the key change. But you want the right cascade started, not the tissue injury cascade started,” Badylak said.

Badylak, who has been working in stem cell-related regenerative medicine for over 20 years, even before stem research became notorious, says his biggest achievement has been watching his initial research go from being just experiments to being used on actual patients. When Badylak first started his research, tissue engineering was not recognized as a scientific discipline. This continued until the 1980s, when, using an animal model to evaluate the reconstruction of blood vessels, he showed that tissues could be reconstructed with certain types of stimulation.

His motivation for continuing his research is simple: his interest in biology, his desire to help people, and curiosity for finding answers to problems that are currently unsolvable.

“I think that the use of extra cellular matrices as a component of regenerative medicine therapy is likely to become very common, [and] that as [we] move from tissue regeneration to organ regeneration, matrix molecules by themselves will not be enough. We need to add to the mix the right cell population and environmental signals that tell that combination of matrix themselves to do the right thing,” Badylak said.

As of now, cardiovascular structures and digits of limbs are the extent of the regenerative therapy. It is not possible to regrow whole organs and limbs just yet. However, the capacity to do so is certainly not out of the question.