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 tolerated, but also capable of providing sustained remission. Preclinical assessment 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 non-tumorigenic in animal hosts. This report describes the development of a murine model that enables in vivo transplantation of 'native' low population doubling level AIDS-KS cells from biopsy-confirmed mucocutaneous lesions. The angiogenic phenotype of in situ AIDS-KS lesions is reconstituted via controlled release of a complete angiogenic peptide, recombinant human basic fibroblast growth factor (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 transplantation 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 striking resemblance, at both the gross and microscopic levels, to in situ AIDS-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 studies, such as assessment of drug clearance at AIDS-KS lesional sites. Finally, applicability of this method is not restricted to AIDS-related malignancies. Establishment and maintenance of an extensive host vascular network should augment success rates for in vivo transplantation of numerous other human cell strains or lines.
Mallery
S R
SR
College of Dentistry, Department of Oral and Maxillofacial Surgery and Pathology and College of Pharmacy, Division of Pharmaceutics, Ohio State University, Columbus, OH 43210, USA. mallery.1@osu.edu
Pei
P
P
Kang
J
J
Zhu
G
G
Ness
G M
GM
Schwendeman
S P
SP
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000818:Animals; D002417:Cattle; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000098:blood supply / Q000473:pathology / Q000821:virology; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012514:Sarcoma, Kaposi / Q000098:blood supply* / Q000473:pathology / Q000821:virology; D012878:Skin Neoplasms / Q000098:blood supply / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014183:Transplantation, Heterologous
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D016222:Fibroblast Growth Factor 2; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid