By Frances Bishopp

Staff Writer

Spun out as a fledgling company from Research Corporation Technologies, Sertoli Technologies Inc. (STI) has taken its first steps toward independence by completing its initial stage in developing a transplant therapy using pancreatic islets and Sertoli cells for Type I diabetes.

Located in Tucson, Ariz., STI, a cellular therapy company, recently completed studies demonstrating that its technology shows islet xenografts (foreign islets) transplanted in both lower and higher animals can survive for an extended period of time.

These results represent a significant milestone in cellular transplantation and should give STI a platform to accelerate development, Shaun Kirkpatrick, STI vice president, told BioWorld Today.

"We will now seek either a pharmaceutical partner or financing and/or a pharmaceutical partnership to help initiate STI's second stage of development," Kirkpatrick said.

STI was created approximately a year ago, when Research Corporation Technologies (RCT), of Tucson, acquired the technology from the University of Tennessee. With an investment of approximately $500,000, the new company was founded.

STI is run by RCT employees, Kirkpatrick said, and RCT will provide the business plans as well as the management until the company moves through an initial phase of feasibility or some seed phase of development.

"Until RCT feels the technology is robust," Kirkpatrick said, "STI will maintain a very virtual profile and, at that point, we will try to wean them away from the entire RCT management funding."

At this point, Kirkpatrick said, the new preclinical results warrant continuation of the company, "scaling up and becoming less virtual," but still being an efficiently run operation.

STI's technology uses Sertoli cells to create immunologically privileged sites in the body where other co-transplanted tissue, such as islets, can survive without sustained immunotherapy.

Sertoli cells comprise a major component of the mammalian testis and are responsible for synthesis of all factors required for testicular immune privilege. These cells nourish and protect developing sperm. Research has found that Sertoli cells also produce substances that inhibit immune rejection.

Affecting more than 650,000 people in the U.S., Type I diabetes, or insulin-dependent, diabetes, is an autoimmune disease, Kirkpatrick explained, which causes the body to destroy the cells in the pancreas that make insulin. These cells are called islets, which are actually clusters of beta cells, he continued.

STI's technology focuses on transplantation of new insulin-producing pancreatic islets to replace those destroyed by disease.

Islet transplantation is preferable to whole organ transplant, since it is a minor surgical procedure. "Large numbers of islets can be stored while whole pancreases cannot," Kirkpatrick said.

Cellular transplantation as a commercial therapy for diseases such as diabetes faces two major obstacles: destruction of the cells by the immune system and lack of available human donor organs. A human islet cell line could solve this supply problem, Kirkpatrick said.

A human islet primary cell line would allow for transplanting allografted tissue, but the technology has not evolved sufficiently to create a viable, reproducible cell line.

Animals are a more feasible source of islets. Pigs particularly are ideal donors because they are readily available, relatively inexpensive and resistant to many viral diseases.

However, due to the great genetic disparity between humans and pigs, porcine islet xenografts elicit a very strong rejection reaction in humans that requires chronic delivery of high doses of immunosuppressive agents.

Preventing or suppressing both islet allograft and xenograft rejection is difficult. To solve this problem, some companies (not STI) have put the islet mass into a capsule. The capsule, which is made mostly of alginate, supposedly lets out what is needed, such as nutrients and insulin, and, at the same time, protects against immune rejection.

Even with the benefits of this technology, long-term survival of discordant, fully functioning islet xenografts has not been achieved.

STI builds on recent discoveries about the immunoprotective function of Sertoli cells. The STI method creates an immunologically privileged site by transplanting a composite of islets and Sertoli cells.

Data has proven that Sertoli cells secrete a factor than inhibits T cell proliferation by suppressing both interleukin-2 (IL-2) production and responsiveness of T cells to IL-2. The data shows that Sertoli cells kill activated T cells by programmed cells death through interaction with Fas ligand.

In short, Sertoli cells create a local environment where xenogenic islets are protected by immune inhibitors and nourished by growth factors. These growth factors, while helping the graft survive, appear to enhance angiogenesis that helps to permanently establish the graft.

Co-transplanted islets and Sertoli cells have survived indefinitely in diabetic rats, with only initial doses of immunotherapy. *