Cell growth - poly

Figure 4b. Cell growth - poly D L-lactic acid film...

Cleek RL, Rege AA, Detmer LA, Eskin SG, Mikos AG. Inhibition of smooth muscle cell growth in vitro by an antisense oligodeoxynucleotide releases from poly(DL-lactic-co-glycolic acid) mictoparticles. J Biomed Mater Res 1997 35 525-530. 

Endothelial cells recovered from both the enzyme (trypsin) recovery system (ERS) and the poly(IPAAm) temperature recovery system (TRS) were subcultured and examined comparatively for cell adhesivity, cell morphology and cell growth activity. The most important finding in the subcultured system was that the TRS exhibited much a higher activity of prostacyclin generation than ERS. It is known that prostacyclin generation is an important function of endothelial cells. 

Fig. 3. A northern blot of poly(A)+ RNA probed with a psi cDNA clone showed enhanced levels of psi messenger RNA as phosphate starvation became more severe. Poly(A)+ RNA was isolated from cultures at 3, 6 and 9 days after transfer to —Pi or +Pi medium (A. Danon et al., unpublished data in preparation). Equal amounts of RNA (1 pg per treatment) were separated on a denaturing formaldehyde/agarose gel and used for a northern blot. The filter was probed using a psi cDNA clone (identified by —/+ screening using standard methods) as the probe. Enhanced levels of mRNA for this clone are seen as early as 3 days after transfer to —Pi medium although cell growth equivalent to the unstressed control continued until day 8.

Poly(amino acids) are insoluble in common solvents, are difficult to fabricate due to high melting point, and absorb a significant amount of water when their acid content reaches over 50 mol%. To solve these problems, polyesters derived from amino acids and lactic acids [e.g., poly (lactic acid-co-lysine) PLAL] are developed. The PLAL system is further modified by reaction with lysine A-carboxyanhydride derivatives. Another modification of poly(amino acids) includes poly(iminocarbon-ates), which are derived from the polymerization of desaminotyrosyl tyrosine alkyl esters. These polymers are easily processable and can be used as support materials for cell growth due to a high tissue compatibility. Mechanical properties of tyrosine-derived poly(carbonates) are in between those of poly(orthoesters) and poly(lactic acid) or poly(gly-colic acid). The rate of degradation of poly(iminocarbonates) is similar to that of poly (lactic acid). 

ADP-ribosylation. In the case of some proteins, multiple ADP-ribose units are transferred to the protein, forming a poly(ADP-ribose) group. The activity of poly (ADP-ribose) polymerase is increased during cell growth, cell differentiation, and recovery from damage to the DNA. The enz)une is involved in controlling the repair of DNA (Satoh et al., 1993). 

Treatment of H35 cells with MIX(poly-L-lysine). The influence of various concentrations of MTX(poly-L-lysine) on both H35 and HSSRq 2 hepatoma cells is illustrated in Figure 1. The effect is also compared to that of the free drug. It is apparent that MTX shows little restraint on the growth of the transport-resistant mutants at levels up to 1 pM in contrast to the wild-type cells which submit to nanomolar concentrations of the drug (I q = 14 nM). However, idien MTX is bound to the poly-L-lysine carrier/ both cell lines show similar characteristics with I 70 nM. The concentrations of poly-L-lysine used in the experiments show little influence on the cell growth. 

Experiments which examine the comparative toxicities of the poly-L- and -D- carriers for hepatocytes and hepatomas indicate a low level of toxicity with the hepatoma. However, an elevated toxic effect is observed for the hepatocyte with the D-isomeric carrier. When the drug is bound to the carrier little alteration is observed in the toxic response of the hepatocyte suggesting that in its resting state it has little requirement for dihydrofolate reductase. The results shown in Table 111 illustrate this point more clearly where only 26Z of reductase activity remains after treating the hepatocytes with 2 micromolar MTX(poly-L-lyaine) yet 752 cellular viability resiains. This contrasts with the response of the hepatoma cell line (Table IV), where both dihydrofolate reductase and 90Z cell growth of both transport defective and non-defective cell lines is eliminated by treatment with 2.8 micromolar MTX(poly-L-lysine). 

TABLE IV Effect of a pulse dose of MTX(poly-L-lysine) on hepatoma cell growth... 

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