Sustained angiogenesis enables in vivo transplantation of mucocutaneous derived AIDS-related Kaposi's sarcoma cells in murine hosts

AIDS-related Kaposi's sarcoma (AIDS-KS), the most prevalent HIV-associated malignancy, is a debilitating, potentially fatal disease. Currently, there is a need for development of AIDS-KS therapies that are not only well toler ated, but also capable of providing sustained remission. Preclinical assess ment of pharmacological parameters and therapeutic efficacies are dependent upon in vivo parameters, However, there are currently no animal KS models and mucocutaneous KS cell isolates have proved to be nontumorigenic in anim al hosts, This report describes the development of a murine model that enab les in vivo transplantation of 'native' low population doubling level AIDS- KS cells from biopsy-confirmed mucocutaneous lesions, The angiogenic phenot ype of in situ AIDS-KS lesions is reconstituted via controlled release of a complete angiogenic peptide, recombinant human basic fibroblast growth fac tor (bFGF), from locally injectable, biodegradable polylactide-co-glycolide implants. Consequential to the sustained local release of bioactive bFGF, a murine vascular network is established, which facilitates the in vivo tra nsplantation of AIDS-KS cells, Desirable aspects of this model include: low cost murine species, transplantation of non-selected patient cells and use of animal hosts that are T cell-deficient, The transplanted human AIDS-KS cells and extensive murine vascular network create lesions that retain a st riking resemblance, at both the gross and microscopic levels, to in situ AI DS-KS tumors. Because the bFGF-induced murine vascular network is analogous to the abundant vascularity present in AIDS-KS lesions, this murine model should provide an excellent vehicle for numerous clinically relevant studie s, such as assessment of drug clearance at AIDS-KS lesional sites. Finally, applicability of this method is not restricted to AIDS-related malignancie s. Establishment and maintenance of an extensive host vascular network shou ld augment success rates for in vivo transplantation of numerous other huma n cell strains or lines.