Nonhuman cells

Glycoproteins produced in nonhuman cells such as plant cells and yeast cells may have a modified glycan structure. Although natural antibodies exist that react with nonhuman glycan structures [18], there is no example of an immune reaction that was mounted to modified glycan structure of a therapeutic protein. 

Advances in recombinant technology alleviated the problem of protein production and its purity. Through the process of recombinant DNA technology and use of nonhuman cell lines, human proteins can be manufactured free of viral contamination. This process enables production of large quantities of proteins previously difficult to obtain from human sources. Further isolation of protein from human sources is associated with a high risk of viral contamination. One such example, plasma derived clotting factor VIII isolated from human blood, resulted in transmission of viral diseases such as hepatitis and AIDS [1,2]. 

This chapter will review some recently completed studies on the long-term effects of MDMA in nonhuman primates. The goals of these studies were to (1) determine if the neurotoxic effects of MDMA, which have been well documented in the rodent (see below), generalize to the primate (2) compare the relative sensitivity of primates and rodents to the neurotoxic effects of MDMA (3) ascertain if the toxic effects of MDMA in the monkey are restricted to nerve fibers (as they are in the rat), or if they involve cell bodies as well (4) evaluate how closely toxic doses of MDMA in the monkey approximate those used by humans and (5) examine whether 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) can be used to detect MDMA-induced serotonergic damage in the CNS of primates. Before presenting the results of these studies, previous results in the... 

Valente AJ, Graves DT, Vialle-Valentin CE, Delgado R, Schwartz CJ. Purification of a monocyte chemotactic factor secreted by nonhuman primate vascular cells in culture. Biochemistry 1988 27(11) 4162 1168. 

Infection by viruses carrying oncogenes can cause malignant cell growth. Although first recognized as causative agents in avian cancers 90 years ago, for much of the twentieth century there was doubt that any human cancers were initiated in this way. Even now, almost all the information in this area refers to nonhuman animals, which presents a number of problems. First, as was already... 

In vitro TGN1412 caused a profound, polyclonal T-cell proliferation of human peripheral blood mononuclear cells, including those from patients with BCLL. It also induced a profound activation and proliferation of T-cell subsets including CD4+ and CD8+ T cells, naive and memory T cells, and regulatory T cells. TGN1412 was shown to induce a transient, well tolerated expansion of T cells in nonhuman primates treated with TGN1412 and efficacy was demonstrated in a rhesus monkey collagen-induced arthritis model. 

Gluck, J.R et al., Early social deprivation in nonhuman primates Long-term effects on survival and cell-mediated immunity, Biol. Psychiatry, 47, 119, 2000. 

MDCK Madin-Darby canine kidney (MDCK) cells have received attention as an alternative to Caco-2 cells for permeability measurements. When grown under standard culture conditions, MDCK cells develop tight junctions and form monolayers of polarized cells. The main advantage over Caco-2 cells is the shorter culture time to confluence (3-5 days). The transep-ithelial electrical resistance of MDCK cells is lower than that of Caco-2 cells and thus, closer to the TEER of the small intestine in vivo. The permeability coefficients of hydrophilic compounds are usually lower in Caco-2 cells than in MDCK cells, which is consistent with the lower TEER values for MDCK cell monolayers. The nonhuman (canine) and nonintestinal (renal) origin of MDCK cells is considered as a disadvantage. They have low expression levels of transporter proteins and low metabolic activity [34], MDCK cells that are stably transfected with P-gp/MDRl are often proposed as an alternative for Caco-2 cells to study bidirectional transport of compounds and, more... 

Calmels B., Ferguson C., Laukkanen M.O., Adler R., Faulhaber M., Kim H.-J., Sellers S., Hematti P., Schmidt M., von Kalle C., Akagi K., Donahue R.E. and Dunbar C.E. (2005) Recurrent retroviral vector integration at the Mdsl/Evil locus in nonhuman primate hematopoietic cells. Blood 2530 2533. 

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