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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

In vitro inhibition of SMC proliferation of various species; rat, rabbit, porcine and human, by alendronate encapsulated in NP (50µM) in comparison to blank NP. Cells were plated, allowed to grow overnight, treated with 50µM alendronate or equal amount of blank NP, incubated for 48hr, and counted using a Coulter counter and MTT assay. The grade of sensitivity obtained was identical for both treatments, rabbit>porcine>rat>>human.
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Figure 7: In vitro inhibition of SMC proliferation of various species; rat, rabbit, porcine and human, by alendronate encapsulated in NP (50µM) in comparison to blank NP. Cells were plated, allowed to grow overnight, treated with 50µM alendronate or equal amount of blank NP, incubated for 48hr, and counted using a Coulter counter and MTT assay. The grade of sensitivity obtained was identical for both treatments, rabbit>porcine>rat>>human.

Mentions: Alendronate loaded NP at 50µM inhibited rat SMC proliferation by 38±10%, and porcine, human, and rabbit SMC were inhibited by 45±16, 22±9 and 72%±21, respectively (Fig. 7). Species sensitivity was ranked, rabbit>porcine>


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)

In vitro inhibition of SMC proliferation of various species; rat, rabbit, porcine and human, by alendronate encapsulated in NP (50µM) in comparison to blank NP. Cells were plated, allowed to grow overnight, treated with 50µM alendronate or equal amount of blank NP, incubated for 48hr, and counted using a Coulter counter and MTT assay. The grade of sensitivity obtained was identical for both treatments, rabbit>porcine>rat>>human.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: In vitro inhibition of SMC proliferation of various species; rat, rabbit, porcine and human, by alendronate encapsulated in NP (50µM) in comparison to blank NP. Cells were plated, allowed to grow overnight, treated with 50µM alendronate or equal amount of blank NP, incubated for 48hr, and counted using a Coulter counter and MTT assay. The grade of sensitivity obtained was identical for both treatments, rabbit>porcine>rat>>human.
Mentions: Alendronate loaded NP at 50µM inhibited rat SMC proliferation by 38±10%, and porcine, human, and rabbit SMC were inhibited by 45±16, 22±9 and 72%±21, respectively (Fig. 7). Species sensitivity was ranked, rabbit>porcine>

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