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Predicting in vivo efficacy of potential restenosis therapies by cell culture studies: species-dependent susceptibility of vascular smooth muscle cells.

Epstein H, Rabinovich L, Banai S, Elazar V, Gao J, Chorny M, Danenebrg HD, Golomb G - Open Cardiovasc Med J (2008)

Bottom Line: Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies.The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (rat>/=rabbit>porcine>human).Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.

ABSTRACT
Although drug-eluting stents (DES) are successfully utilized for restenosis therapy, the development of local and systemic therapeutic means including nanoparticles (NP) continues. Lack of correlation between in vitro and in vivo studies is one of the major drawbacks in developing new drug delivery systems. The present study was designed to examine the applicability of the arterial explant outgrowth model, and of smooth muscle cells (SMC) cultures for prescreening of possible drugs. Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies. The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (rat>/=rabbit>porcine>human). Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive. The validity of in vitro culture studies for the screening of controlled release delivery systems such as nanoparticles is limited. It is suggested that prescreening studies of possible drug candidates for restenosis therapy should include both SMC cell cultures of rat and human, appropriately designed with a suitable serum.

No MeSH data available.


Related in: MedlinePlus

Mitotic index of SMC proliferation of various species. Cells were plated at 1.5*104 cells per well in 24-well plates, and the rate of replication was compared 6 days following seeding. The cell replication rate was calculated as log2 (number of cells 6 days after plating / number of cells 24hr after plating). Porcine derived SMC were found as the most rapidly proliferating cells among the species examined. p<0.001 and p<0.05, porcine and human SMC vs. other species, respectively.
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Figure 3: Mitotic index of SMC proliferation of various species. Cells were plated at 1.5*104 cells per well in 24-well plates, and the rate of replication was compared 6 days following seeding. The cell replication rate was calculated as log2 (number of cells 6 days after plating / number of cells 24hr after plating). Porcine derived SMC were found as the most rapidly proliferating cells among the species examined. p<0.001 and p<0.05, porcine and human SMC vs. other species, respectively.

Mentions: The mitotic index of SMC proliferation was determined for all species, porcine derived cells exhibited the highest mitotic rate among the species examined ranking, porcine≥rat>>rabbit>human (Fig. 3).


Predicting in vivo efficacy of potential restenosis therapies by cell culture studies: species-dependent susceptibility of vascular smooth muscle cells.

Epstein H, Rabinovich L, Banai S, Elazar V, Gao J, Chorny M, Danenebrg HD, Golomb G - Open Cardiovasc Med J (2008)

Mitotic index of SMC proliferation of various species. Cells were plated at 1.5*104 cells per well in 24-well plates, and the rate of replication was compared 6 days following seeding. The cell replication rate was calculated as log2 (number of cells 6 days after plating / number of cells 24hr after plating). Porcine derived SMC were found as the most rapidly proliferating cells among the species examined. p<0.001 and p<0.05, porcine and human SMC vs. other species, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2570571&req=5

Figure 3: Mitotic index of SMC proliferation of various species. Cells were plated at 1.5*104 cells per well in 24-well plates, and the rate of replication was compared 6 days following seeding. The cell replication rate was calculated as log2 (number of cells 6 days after plating / number of cells 24hr after plating). Porcine derived SMC were found as the most rapidly proliferating cells among the species examined. p<0.001 and p<0.05, porcine and human SMC vs. other species, respectively.
Mentions: The mitotic index of SMC proliferation was determined for all species, porcine derived cells exhibited the highest mitotic rate among the species examined ranking, porcine≥rat>>rabbit>human (Fig. 3).

Bottom Line: Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies.The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (rat>/=rabbit>porcine>human).Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive.

View Article: PubMed Central - PubMed

Affiliation: Dept. of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.

ABSTRACT
Although drug-eluting stents (DES) are successfully utilized for restenosis therapy, the development of local and systemic therapeutic means including nanoparticles (NP) continues. Lack of correlation between in vitro and in vivo studies is one of the major drawbacks in developing new drug delivery systems. The present study was designed to examine the applicability of the arterial explant outgrowth model, and of smooth muscle cells (SMC) cultures for prescreening of possible drugs. Elucidation of different species sensitivity (rat, rabbit, porcine and human) to diverse drugs (tyrphostins, heparin and bisphsophonates) and a delivery system (nanoparticles) could provide a valuable screening tool for further in vivo studies. The anticipated sensitivity ranking from the explant outgrowth model and SMC mitotic rates (porcine>rat>rabbit>human) do not correlate with the observed relative sensitivity of those animals to antiproliferative therapy in restenosis models (rat>/=rabbit>porcine>human). Similarly, the inhibitory profile of the various antirestenotic drugs in SMC cultures (rabbit>porcine>rat>human) do not correlate with animal studies, the rabbit- and porcine-derived SMC being highly sensitive. The validity of in vitro culture studies for the screening of controlled release delivery systems such as nanoparticles is limited. It is suggested that prescreening studies of possible drug candidates for restenosis therapy should include both SMC cell cultures of rat and human, appropriately designed with a suitable serum.

No MeSH data available.


Related in: MedlinePlus