Testes May Provide Plentiful Source of Adult Stem Cells

NEW YORK, Sept. 19 -- A method to harvest stem cells from adult testes and reprogram them into functional tissue may provide an easily accessible and plentiful alternative to controversial embryonic stem cells, researchers said.

In a mouse study, spermatogonial progenitor stem cells isolated from testes using a marker on the cell surface were successfully redirected in vivo into working endothelial cells and tissue, contractile cardiac tissue, brain cells, and other cell types, reported Shahin Rafii, M.D., of Weill Cornell Medical College here, and colleagues in the Sept. 20 issue of Nature.

If the process works in humans, it could have therapeutic use for men in heart attack, stroke, Alzheimer's disease, Parkinson's disease, diabetes, and restoring fertility after chemotherapy, Dr. Rafii said.

"And, since these cells come from the patient's own tissue, they are genetically compatible and they are not going to get rejected," he added.

Other research groups have also pursued organ-specific adult stem cells as a substitute for embryonic stem cells. However, stem cells are relatively scarce in adult organs and have proven difficult to identify and harvest.

Dr. Rafii's group started studying adult testes as a source of pluripotent stem cells when he noticed that many testicular cancer patients develop teratoma tumors, which contain different types of tissue.

This suggested that testicular cancer cells share characteristics with adult stem cells. Thus, the spermatogonia cells that generate the precursors to sperm and give rise to teratomas might be easier to reprogram than other adult stem cells.

But, like other research groups, Dr. Rafii and colleagues had trouble finding and tracking these cells.

Then while evaluating a large series of knockout mice, his group discovered a stem and progenitor cell surface marker--GPR125--expressed on the adult testis.

Immunohistochemistry showed that the mice expressed GPR125 in the testis only in spermatogonial stem and progenitor cells and not in differentiated germ cells.

The marker was used to harvest and expand adult spermatogonia cells, which continued to proliferate when cultivated in the lab long-term. The cells could also be cultured into undifferentiated embryonic-like stem cells that expressed a marker for pluipotency.

The cells could be differentiated into multiple tissue types in vitro, including rhythmically contractile cardiac tissue and an "extensive network of vessel-like, lumen-containing" structures.

When the stem cells were implanted in immunodeficient mice used for cancer research, the cells developed into teratomas in every case that showed differentiation into multiple types of cells.

In the same mouse model, the stem cells formed teratomas that contained functional blood vessels that joined up with the "host" circulation system.

However, some hurdles remain before the method could be used in men, the researchers said.

The precise molecular and cellular pathways to switch spermatogonial stem and progenitor cells into differentiable stem cells on demand are not clear.

However, the GPR125 marker for identifying stem and progenitor cells is found in human testes as well, Dr. Rafii said.

The researchers said they have not seen cancer or cancer-promoting activity in adult mice implanted with differentiated cell tissue derived from testes, but "the use of these cells for therapeutic purposes should proceed with caution and extensive preclinical experimentation."

The technology is still experimental, Dr. Rafii concluded, "but our paper is one step forward."