Human tissue slices

Use of Human Tissue Slices in Drug Targeting Research... 

Figure 11.25. Raman microspectroscopy of a human tissue slice from a prostate cancer biopsy specimen mounted in paraffin. Scale on video image is in microns.

Nave R, Fisher R, Zech K (2006) In vitro metabolism of ciclesonide in human lung and liver precision-cut tissue slices. Biopharm Drug Dispos 27 197-207. 

Ressmeyer AR, Larsson AK, Vollmer E, Dahlen SE, Uhlig S, Martin C (2006) Characterisation of guinea pig precision-cut lung slices comparison with human tissues. Eur Respir J 28 603-611. 

Experimental samples are mainly derived from tissue culture cells, laboratory animals, or human tissues collected from hospitals after surgical biopsies and autopsies. With human and animal tissue specimens, it is important to arrest metabolic processes within 5-10 min of collection in order to preserve mRNAs from degradation by internal enzymatic reactions (26,27). Most hospitals use 10% buffered formalin as a tissue fixative. Subsequently, each tissue slice is trapped in a paraffin block. Series of 4-5-pm-thick sections are cut and mounted on silanated slides. Formalin-fixed archival tissues have been successfully used in in situ PCR and in situ hybridization protocols (28-32). However, the procedure for RNA protection is not always followed. It is often difficult to alter or control the routine procedures of hospitals for the required protection of mRNAs in surgically removed human tissues. 

The blockade of A3AR with the selective antagonist, MRS 1334, improves the stability of GABAAergic neurotransmission, as assessed in a patch clamp study on GABAa receptor isolated from neurosurgically resected epileptic human nervous tissues and microtransplanted into Xenopus oocytes, and on human epileptic slices obtained from neurosurgical resection (Roseti et al. 2008). 

Quantitative differences have been observed between humans and animals regarding noradrenaline release from neocortical slices release in human tissue was inhibited by H3 receptor activation to a much lower extent than in mouse neocortex (see Stark et al. 2004). 

Yl, Yielding, K. L., Tomkins, G. M., and Bunim, J. J., Synthesis of hyaluronic acid by human synovial tissue slices. Science 125, 1300 (1957). 

In a more recent study, peroxidative and nephrotoxic injuries induced by meropenem and imipenem/ cilastatin in rat and human cortical slices and micro-somes were compared to those induced by cephaloridine [9]. While meropenem and imipenem/cilastatin did produce lipid peroxidation and depressed PAH accumulation and gluconeogenesis in rat and human renal cortex, the effect was substantially less than with cephaloridine [9]. The human renal cortical tissue appears to be less susceptible to p-lactam induced lipid peroxidation than the rat renal cortical tissue with meropenem showed lower renal toxicity then imipenem/cilastatin [9]. 

During preclinical development the metabolite structures of potential new drug candidates are typically identified via in vitro tools such as subcellular liver fractions (microsomes, S9), expressed human enzymes, or cellular systems (e.g., hepatocytes, tissue slices) [25]. The metabolism observed in the different systems is compared across species, with the aim that all the metabolites formed in human in vitro systems can also be identified in the systems originating from the animal species used in major toxicity studies. 

These results demonstrate that, at the concentration used, PBO did not induce UDS in cultured human liver slices. The fact that the three known gero-toxins did produce a significant increase in UDS is testament to the functional viability of the huttian tissue used in this study, as all three compounds have been shown to undergo metabolic activation by human liver cytochrome P-450 isoenzymes (Gonzalez es a ., 1991),... 

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