Parenteral administration of xenogenic fetal materials to old rats had been shown by Kment and coworkers in the 1960ies and 1970ies to compensate for at least some age-related losses of physiological capacity in aged rats. In a number of studies in the 1980ies, then commercially available lyophilized homogenates of fetal sheep testis given subcutaneously (s.c.) to aged rats produced statistically significant long-acting revitalizing effects on a number of age parameters of connective tissue, skin, aorta, liver, kidney, heart, spontaneous and reactive motor activity, running capacity, learning and memory, plasma testosterone as well as on cohort survival after the age of 24 months. A lyophilized fetal sheep mesenchymal preparation (obtained from umbilical cord) had even more pronounced revitalizing effects on old male rats including significantly elevated testosterone levels. In another survival study, female OF-1 mice showing age-related expression of lymphatic leucosis were given a single block of 5 s.c. injections of fetal sheep mesenchyme or Ringer's solution, respectively, at the age of 50%-survival. Survival curves separated within weeks: the last controls died at the age of 700 days whereas the last animals of the treated group attained an age of 1100 days. In order to elucidate the mechanism of this effect, we are using the YAC-1 mouse lymphoma cell line. A series of cell culture proliferation studies showed two opposite effects of the complex material: a clearly dose-related stimulatory effect at low concentrations, and a proliferation-blocking effect at higher concentrations which seems to arrest the cell cycle of the lymphoma cells (probably in G1 or G0) or sends them into apoptosis. These effects are abolished by heat denaturation and were not obtained by addition of xenogenic albumin. First studies with a cell death detection test point to high apoptotic activity induced by the fetal material. Hypothetical signal transduction mechanisms and testing strategies are discussed.
xenogenic fetal mesenchyme