The spheramine project is not the Sertoli cell project. The spheramines use human retinal epithelial cells on TTP's proprietary microcarriers.
The Sertoli cell project on the other hand is somewhat on the backburner, but the rationale was described as follows in the Oct98 NI:
"Sertoli cells are obtained from porcine testes. Tissue from the testes has long been known to be ‘immune privileged'; one can transplant testicular tissue without triggering immune system rejection. Sertoli cells appear to be at the heart of this exempt status. They play a central role in the embryonic differentiation of male gonads and later in the regulation of spermatogenesis. Sertoli cells produce a cornucopia of substances involved in cell growth and differentiation, which provide them with their role in facilitating the xenotransplantation of neural cells. By secreting a ligand for a molecule on the surface of T-cells called CD 95, or fas, they accelerate the process by which excess T-cells are normally expunged though apoptosis, part of the regulatory feedback loops maintaining systemic homeostasis. Active T-cells secrete fas, but they generally do not become vulnerable to apoptotic activation by fas until their surveillance/protective activity is finished. By providing the fas ligand, Sertoli cells supply the ‘link' by which fas triggers cell death in T-cells, before they can 'recognize' the implanted cells. They also reduce the production of interleukin-2, which in turn suppresses T-cell production. Secondly, Sertoli cells appear to secrete neural growth factors themselves, including GDNF, and separate studies have shown that GDNF enhances implant survival in animal models. Injecting Sertoli cells alone into the damaged striatal regions of rats in a surgical model reduces Parkinsonian symptoms. It has been hypothesized (but not proven) that Sertoli cells may also activate neural stem cells that persist in the brain into adulthood.
Initial preclinical studies have shown that stereotaxically inserted porcine Sertoli cells, co-inserted with bovine dopaminergic cells, enhance the sprouting of dopaminergic neurons and reverse lesions in a Parkinson's model. Formal cell-counting studies have not been carried out, but the Company believes that up to 70-80% of implanted cells survive, which if confirmed, would far exceed the current 5-10% survival described for fetal cell and porcine cell implants with cyclosporine or Diacrin's masking technique. "
Since it is the spheramine program which received the grant and is moving towards an IND, this may be moot, but perhaps is of academic interest.
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