Cells for Building

Tissue engineering has taken on a new meaning in recent years, bringing the stuff of science fiction to the operating table.

Charles Vacanti
Nov 21, 2004
<p>FRA ANGELICA'S "HEALING OF JUSTINIAN"</p>

Scala/Art Resource, NY

Tissue engineering has taken on a new meaning in recent years, bringing the stuff of science fiction to the operating table. Bone, cartilage, skin, and other organ tissues can now be grown from stem cells and implanted. Pushing beyond the mechanics of prosthetics, the advances in stem-cell biology and materials science have enabled startling accomplishments, including the replacement of a human breastbone, a thumb, and a rat spinal cord.

But, connections to the embryonic stem-cell ethical minefield bring a renewed need to evaluate our best options in moving forward. As the name implies, pluripotent embryonic stem cells are rife with potential but also with confounding factors even outside philosophical quagmires. I believe that further work with adult stem cells, which may skirt both ethical and technical difficulties, will lead us toward more success with tissue engineering.

HISTORIC STRIDES

A painting by Fra...

THE RIGHT CELLULAR STUFF

To be effective, cells must be easily procured and readily available; they must multiply well without losing their potential to generate new functional tissue; they should not be rejected by the recipient and not turn into cancer; and they must have the ability to survive in the low-oxygen environment normally associated with surgical implantation.

Mature adult cells fail to meet many of these criteria. The oxygen demand of cells increases with their metabolic activity. After being expanded in the incubator for significant periods of time, they have a relatively high oxygen requirement and do not perform normally. A hepatocyte, for example, requires about 50 times more oxygen than a cell such as a chondrocyte. So, much attention has turned to progenitor cells and stem cells.

True stem cells can turn into any type of cell, while progenitor cells are more or less committed to becoming cell types of a particular tissue or organ. Adult stem cells may actually represent progenitor cells in that they may turn into all the cells of a specific tissue but not into any cell type. Adult stem cells can be procured from the individual needing the new tissue and thus not be rejected. Since these cells are immature, they will survive a low-oxygen environment.

<p>Charles Vacanti</p>

Courtesy of Charles Vacanti

Although embryonic stem cells have been shown to have the potential to turn into virtually any cell type found within the body, no studies have demonstrated the controlled generation of a uniform cell type. And unless they are derived from somatic-cell nuclear transfer, embryonic stem cells will be rejected by a recipient.

In 2001 we discovered an adult stem cell, which we refer to as a "spore-like" cell, in virtually every tissue of the body.5 These small cells, measuring 3 to 7 μm, have the ability to withstand hostile environments such as low oxygen, elevated temperature, and freeze-thaw cycles. I believe that the numerous adult stem cells and progenitor cells being described are all offspring of the same spore-like stem cell. In our studies we have learned that, as these cells develop and mature, they have the ability to turn into virtually any cell type seen in the body.

Based on experiments in our laboratory, I believe that spore-like adult stem cells are the body's natural repair cells activated by injury. When activated, they multiply and are programmed to mature and repair damaged tissue. Incidentally, if the damage is sufficient, these cells may lose their local environmental cues and remain in their high-multiplication phase without maturing. In this state they may have the potential to turn into cancer. These tiny, spore-like cells are small enough to be transported via the lymphatic system, enabling metastasis. Although I have no evidence to verify this hypothesis, it is an internally consistent model that may explain both the natural process of repair, and repair gone awry.

Regardless, such stem cells may ultimately allow physicians and scientists to repair or replace any tissue in the human body. The potential to reverse the symptoms of stroke and other central nervous system diseases such as Parkinson and Alzheimer is quite realistic. It may be possible to remove cells from diseased organs, genetically manipulate them, and return them to patients to cure their disease.

ADULT VS. EMBRYONIC

<p>SEEDS FOR NEW CURES:</p>

Laboratory for Tissue Engineering and Regenerative Medicine, Brigham and Women's Hospital and Harvard Medical School

Transmission electron micrograph of extremely small "spore-like" adult stem cells found in virtually every tissue of the body. They could be repair cells capable of turning into the mature cells of the organ or tissue from which they were initially isolated.

Both embryonic and adult stem cells appear to have similar potential to develop into the different cellular elements necessary for effective tissue replacement. The differences are few, but they may be significant. Some scientists believe that embryonic stem cells may have a greater ability to produce healthier tissue. This may or may not be the case.

My view may be biased, but after a careful review of the literature, I have concluded that the disadvantages of embryonic stem cells appear to outweigh the advantages. Embryonic stem cells will be recognized as foreign and be rejected. There is no evidence that embryonic stem cells can be consistently driven to uniformly generate only the cell type that is needed. While they can certainly be encouraged to form any type of cell, many other types of cells are usually generated at the same time. New nerve cells may be contaminated with bone or muscle, for example.

Perhaps most significant are the moral and ethical considerations surrounding the use of embryonic stem cells. Whether the embryo is a human being, or a meaningless aggregation of cells, remains unknown. If it is a worthless aggregate of living cells, then we may do well to undertake scientific investigations. If, on the other hand, the human embryo indeed represents a human being, then I believe it would be immoral to conduct scientific investigations.

If, at some point in time, an embryonic stem cell is determined to represent human life, we will be poorly judged as a society. When considering the seriousness of the issue, it seems reasonable to first demonstrate whether there is any real advantage to using embryonic cells, by studying nonhuman species, as this is a prerequisite in any other investigative field.

Charles Vacanti is the Vandam/Covino Professor of Anesthesia in the Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Medical School, and anesthesiologist-in-chief at Brigham and Women's Hospital. He is one of four brothers involved in tissue engineering research and has repeatedly shaken the field with daring experiments and ideas for creating new implantable tissue.

He can be contacted at cvacanti@partners.org

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