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Liposomal tacrolimus administered systemically and within the donor cell suspension improves xenograft survival in hemiparkinsonian rats

Identifieur interne : 000137 ( PascalFrancis/Curation ); précédent : 000136; suivant : 000138

Liposomal tacrolimus administered systemically and within the donor cell suspension improves xenograft survival in hemiparkinsonian rats

Auteurs : A. Y. Alemdar [Canada] ; K. A. Baker [Canada] ; D. Sadi [Canada] ; V. C. Mcalister [Canada] ; I. Mendez [Canada]

Source :

RBID : Pascal:02-0290345

Descripteurs français

English descriptors

Abstract

The most widely used immunosuppressant in neural transplantation is cyclosporine- A (CsA). However, CsA has significant toxic effects when administered systemically. Tacrolimus (FK506), is a more potent immunosuppressant than CsA and can be prepared in lipid micelles (LTAC). This liposomal preparation allows for the administration of tacrolimus to the site of transplantation, possibly reducing the systemic side effects of immunosuppression. In this study we investigated the ability of LTAC to promote graft survival in hemiparkinsonian rats implanted with fetal mouse xenografts when LTAC is administered systemically to the host, when added to the donor cell suspension, or in combination. Rats with unilateral 6-hydroxydopamine lesions were transplanted with 800,000 fetal mouse ventral mesencephalic (VM) cells and were randomly divided into four groups. Group 1 was not immunosuppressed; Group 2 received daily systemic injections of LTAC; Group 3 received LTAC within the cell suspensions of mouse VM cells; and Group 4 received LTAC in the cell suspensions along with daily systemic administration of LTAC. Transplanted rats were assessed for rotational behavior 3 and 6 weeks posttransplantation. Cell survival was assessed using tyrosine hydroxylase (TH) immunohistochemistry. A significant reduction in rotational scores was observed only in the group of animals receiving the combination of LTAC-treated donor cells and systemic LTAC administration. This functional improvement correlated with a significantly greater survival of TH-immunoreactive cells in this group of animals. The other groups had poor cell survival and no significant functional improvement. We conclude that a combination of systemic immunosuppression and treatment of the cell suspension with LTAC may be a superior strategy to optimize xenograft survival. This strategy may have important implications for clinical neural transplantation.
pA  
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A08 01  1  ENG  @1 Liposomal tacrolimus administered systemically and within the donor cell suspension improves xenograft survival in hemiparkinsonian rats
A11 01  1    @1 ALEMDAR (A. Y.)
A11 02  1    @1 BAKER (K. A.)
A11 03  1    @1 SADI (D.)
A11 04  1    @1 MCALISTER (V. C.)
A11 05  1    @1 MENDEZ (I.)
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C01 01    ENG  @0 The most widely used immunosuppressant in neural transplantation is cyclosporine- A (CsA). However, CsA has significant toxic effects when administered systemically. Tacrolimus (FK506), is a more potent immunosuppressant than CsA and can be prepared in lipid micelles (LTAC). This liposomal preparation allows for the administration of tacrolimus to the site of transplantation, possibly reducing the systemic side effects of immunosuppression. In this study we investigated the ability of LTAC to promote graft survival in hemiparkinsonian rats implanted with fetal mouse xenografts when LTAC is administered systemically to the host, when added to the donor cell suspension, or in combination. Rats with unilateral 6-hydroxydopamine lesions were transplanted with 800,000 fetal mouse ventral mesencephalic (VM) cells and were randomly divided into four groups. Group 1 was not immunosuppressed; Group 2 received daily systemic injections of LTAC; Group 3 received LTAC within the cell suspensions of mouse VM cells; and Group 4 received LTAC in the cell suspensions along with daily systemic administration of LTAC. Transplanted rats were assessed for rotational behavior 3 and 6 weeks posttransplantation. Cell survival was assessed using tyrosine hydroxylase (TH) immunohistochemistry. A significant reduction in rotational scores was observed only in the group of animals receiving the combination of LTAC-treated donor cells and systemic LTAC administration. This functional improvement correlated with a significantly greater survival of TH-immunoreactive cells in this group of animals. The other groups had poor cell survival and no significant functional improvement. We conclude that a combination of systemic immunosuppression and treatment of the cell suspension with LTAC may be a superior strategy to optimize xenograft survival. This strategy may have important implications for clinical neural transplantation.
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Pascal:02-0290345

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<div type="abstract" xml:lang="en">The most widely used immunosuppressant in neural transplantation is cyclosporine- A (CsA). However, CsA has significant toxic effects when administered systemically. Tacrolimus (FK506), is a more potent immunosuppressant than CsA and can be prepared in lipid micelles (LTAC). This liposomal preparation allows for the administration of tacrolimus to the site of transplantation, possibly reducing the systemic side effects of immunosuppression. In this study we investigated the ability of LTAC to promote graft survival in hemiparkinsonian rats implanted with fetal mouse xenografts when LTAC is administered systemically to the host, when added to the donor cell suspension, or in combination. Rats with unilateral 6-hydroxydopamine lesions were transplanted with 800,000 fetal mouse ventral mesencephalic (VM) cells and were randomly divided into four groups. Group 1 was not immunosuppressed; Group 2 received daily systemic injections of LTAC; Group 3 received LTAC within the cell suspensions of mouse VM cells; and Group 4 received LTAC in the cell suspensions along with daily systemic administration of LTAC. Transplanted rats were assessed for rotational behavior 3 and 6 weeks posttransplantation. Cell survival was assessed using tyrosine hydroxylase (TH) immunohistochemistry. A significant reduction in rotational scores was observed only in the group of animals receiving the combination of LTAC-treated donor cells and systemic LTAC administration. This functional improvement correlated with a significantly greater survival of TH-immunoreactive cells in this group of animals. The other groups had poor cell survival and no significant functional improvement. We conclude that a combination of systemic immunosuppression and treatment of the cell suspension with LTAC may be a superior strategy to optimize xenograft survival. This strategy may have important implications for clinical neural transplantation.</div>
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<s5>354000100103130150</s5>
</fA43>
<fA44>
<s0>0000</s0>
<s1>© 2002 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45>
<s0>52 ref.</s0>
</fA45>
<fA47 i1="01" i2="1">
<s0>02-0290345</s0>
</fA47>
<fA60>
<s1>P</s1>
</fA60>
<fA61>
<s0>A</s0>
</fA61>
<fA64 i1="01" i2="1">
<s0>Experimental neurology : (Print)</s0>
</fA64>
<fA66 i1="01">
<s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>The most widely used immunosuppressant in neural transplantation is cyclosporine- A (CsA). However, CsA has significant toxic effects when administered systemically. Tacrolimus (FK506), is a more potent immunosuppressant than CsA and can be prepared in lipid micelles (LTAC). This liposomal preparation allows for the administration of tacrolimus to the site of transplantation, possibly reducing the systemic side effects of immunosuppression. In this study we investigated the ability of LTAC to promote graft survival in hemiparkinsonian rats implanted with fetal mouse xenografts when LTAC is administered systemically to the host, when added to the donor cell suspension, or in combination. Rats with unilateral 6-hydroxydopamine lesions were transplanted with 800,000 fetal mouse ventral mesencephalic (VM) cells and were randomly divided into four groups. Group 1 was not immunosuppressed; Group 2 received daily systemic injections of LTAC; Group 3 received LTAC within the cell suspensions of mouse VM cells; and Group 4 received LTAC in the cell suspensions along with daily systemic administration of LTAC. Transplanted rats were assessed for rotational behavior 3 and 6 weeks posttransplantation. Cell survival was assessed using tyrosine hydroxylase (TH) immunohistochemistry. A significant reduction in rotational scores was observed only in the group of animals receiving the combination of LTAC-treated donor cells and systemic LTAC administration. This functional improvement correlated with a significantly greater survival of TH-immunoreactive cells in this group of animals. The other groups had poor cell survival and no significant functional improvement. We conclude that a combination of systemic immunosuppression and treatment of the cell suspension with LTAC may be a superior strategy to optimize xenograft survival. This strategy may have important implications for clinical neural transplantation.</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002B02B06</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Tacrolimus</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Tacrolimus</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Tacrolimús</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Hétérogreffe</s0>
<s5>03</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Heterograft</s0>
<s5>03</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Heteroinjerto</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Ciclosporine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Ciclosporin</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Ciclosporina</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>05</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Tyrosine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Tyrosine</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>06</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Tirosina</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>06</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Immunohistochimie</s0>
<s5>08</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Immunohistochemistry</s0>
<s5>08</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Inmunohistoquímica</s0>
<s5>08</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Parkinson maladie</s0>
<s5>10</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Parkinson disease</s0>
<s5>10</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Parkinson enfermedad</s0>
<s5>10</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE">
<s0>Chimiothérapie</s0>
<s5>13</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG">
<s0>Chemotherapy</s0>
<s5>13</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA">
<s0>Quimioterapia</s0>
<s5>13</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE">
<s0>Implant</s0>
<s5>16</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG">
<s0>Implant</s0>
<s5>16</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA">
<s0>Implante</s0>
<s5>16</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE">
<s0>Immunodépresseur</s0>
<s5>17</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG">
<s0>Immunosuppressive agent</s0>
<s5>17</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA">
<s0>Inmunodepresor</s0>
<s5>17</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE">
<s0>Survie</s0>
<s5>18</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG">
<s0>Survival</s0>
<s5>18</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA">
<s0>Sobrevivencia</s0>
<s5>18</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE">
<s0>Rat</s0>
<s5>19</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG">
<s0>Rat</s0>
<s5>19</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA">
<s0>Rata</s0>
<s5>19</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE">
<s0>Animal</s0>
<s5>20</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG">
<s0>Animal</s0>
<s5>20</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA">
<s0>Animal</s0>
<s5>20</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE">
<s0>Toxicité</s0>
<s5>21</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG">
<s0>Toxicity</s0>
<s5>21</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA">
<s0>Toxicidad</s0>
<s5>21</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE">
<s0>Immunodépression</s0>
<s5>22</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG">
<s0>Immunosuppression</s0>
<s5>22</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA">
<s0>Inmunodepresión</s0>
<s5>22</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE">
<s0>Souris</s0>
<s5>23</s5>
</fC03>
<fC03 i1="15" i2="X" l="ENG">
<s0>Mouse</s0>
<s5>23</s5>
</fC03>
<fC03 i1="15" i2="X" l="SPA">
<s0>Ratón</s0>
<s5>23</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE">
<s0>Lactone</s0>
<s5>25</s5>
</fC03>
<fC03 i1="16" i2="X" l="ENG">
<s0>Lactone</s0>
<s5>25</s5>
</fC03>
<fC03 i1="16" i2="X" l="SPA">
<s0>Lactona</s0>
<s5>25</s5>
</fC03>
<fC03 i1="17" i2="X" l="FRE">
<s0>Macrocycle</s0>
<s5>26</s5>
</fC03>
<fC03 i1="17" i2="X" l="ENG">
<s0>Macrocycle</s0>
<s5>26</s5>
</fC03>
<fC03 i1="17" i2="X" l="SPA">
<s0>Macrociclo</s0>
<s5>26</s5>
</fC03>
<fC03 i1="18" i2="X" l="FRE">
<s0>Aminoacide</s0>
<s5>27</s5>
</fC03>
<fC03 i1="18" i2="X" l="ENG">
<s0>Aminoacid</s0>
<s5>27</s5>
</fC03>
<fC03 i1="18" i2="X" l="SPA">
<s0>Aminoácido</s0>
<s5>27</s5>
</fC03>
<fC03 i1="19" i2="X" l="FRE">
<s0>Traitement</s0>
<s5>35</s5>
</fC03>
<fC03 i1="19" i2="X" l="ENG">
<s0>Treatment</s0>
<s5>35</s5>
</fC03>
<fC03 i1="19" i2="X" l="SPA">
<s0>Tratamiento</s0>
<s5>35</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Rodentia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Mammalia</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Vertebrata</s0>
<s2>NS</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Greffe</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Graft</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Injerto</s0>
<s5>37</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Système nerveux pathologie</s0>
<s5>61</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Nervous system diseases</s0>
<s5>61</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Sistema nervioso patología</s0>
<s5>61</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Système nerveux central pathologie</s0>
<s5>62</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Central nervous system disease</s0>
<s5>62</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Sistema nervosio central patología</s0>
<s5>62</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Encéphale pathologie</s0>
<s5>63</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Cerebral disorder</s0>
<s5>63</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Encéfalo patología</s0>
<s5>63</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE">
<s0>Extrapyramidal syndrome</s0>
<s5>64</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG">
<s0>Extrapyramidal syndrome</s0>
<s5>64</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA">
<s0>Extrapiramidal síndrome</s0>
<s5>64</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE">
<s0>Maladie dégénérative</s0>
<s5>65</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG">
<s0>Degenerative disease</s0>
<s5>65</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA">
<s0>Enfermedad degenerativa</s0>
<s5>65</s5>
</fC07>
<fN21>
<s1>169</s1>
</fN21>
<fN82>
<s1>PSI</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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   |wiki=    Wicri/Canada
   |area=    ParkinsonCanadaV1
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   |texte=   Liposomal tacrolimus administered systemically and within the donor cell suspension improves xenograft survival in hemiparkinsonian rats
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