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The influence of donor age on the survival of solid and suspension intraparenchymal human embryonic nigral grafts

Identifieur interne : 000D92 ( Main/Corpus ); précédent : 000D91; suivant : 000D93

The influence of donor age on the survival of solid and suspension intraparenchymal human embryonic nigral grafts

Auteurs : Thomas B. Freeman ; Paul R. Sanberg ; G. Michael Nauert ; Barbara D. Boss ; Dennis Spector ; C. Warren Olanow ; Jeffrey H. Kordower

Source :

RBID : ISTEX:1AA361AFAC1D975EF627F0E0745195D0BC1BD003

Abstract

In many species, graft survival and graft-derived behavioral recovery are affected by the embryonic donor age. We compared the ability of solid and suspension grafts of human embryonic mesencephalic dopaminergic (DA) neurons at different embryonic stages to survive intraparenchymal transplantation into 6-OHDA lesioned immunosuppressed rats. Suspension grafts survived best when donor age was between postconception (PC) days 34 and 56. Transplants displayed numerous healthy tyrosine hydroxylase immunoreactive (TH-IR) neurons which sent extensive neuritic processes into the host striatum. Suspension grafts survived poorly when donor age was greater than 65 days. Solid implants displayed comparable viability of TH-IR neurons when donor age was between 44 and 65 days. No solid grafts contained TH-IR cells when donor tissue was older than 72 days. The suspension and solid methods of transplantation resulted in comparable survival of robust grafts, but solid grafts resulted in more intergraft variability than suspension grafts, particularly among the more marginal implants. Our results demonstrate that the upper limit for survival of human embryonic DA suspension grafts correlates well with the period of development of the human nigrostriatal pathway. The “window” for donor age of solid human embryonic DA grafts appears to be extended by about 9 days in comparison to suspension grafts. These data suggest that the upper age limit for grafting human mesencephalic DA neurons should be PC day 56 for suspension grafts, and PC day 65 for solid implants. Older donors are likely to produce grafts with fewer surviving DA neurons.

Url:
DOI: 10.1016/0963-6897(94)00048-O

Links to Exploration step

ISTEX:1AA361AFAC1D975EF627F0E0745195D0BC1BD003

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<ce:textfn>Department of Pharmacology and Experimental Therapeutics, University of South Florida, Columbia Drive, Suite 730, Tampa, FL 33606, USA</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF3">
<ce:label>c</ce:label>
<ce:textfn>Department of Psychiatry, University of South Florida, Columbia Drive, Suite 730, Tampa, FL 33606, USA</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF4">
<ce:label>d</ce:label>
<ce:textfn>Woman's Center, Tampa, FL, USA</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF5">
<ce:label>e</ce:label>
<ce:textfn>Hana Biologics, Inc., Alameda, CA, USA</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF6">
<ce:label>f</ce:label>
<ce:textfn>Department of Neurology, Mount Sinai Medical Center, New York, NY, USA</ce:textfn>
</ce:affiliation>
<ce:affiliation id="AFF7">
<ce:label>g</ce:label>
<ce:textfn>Department of Neurological Sciences, Rush Presbyterian Medical Center, Chicago, IL, USA</ce:textfn>
</ce:affiliation>
<ce:correspondence id="COR1">
<ce:label>1</ce:label>
<ce:text>To whom correspondence should be addressed.</ce:text>
</ce:correspondence>
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<ce:date-accepted day="6" month="9" year="1994"></ce:date-accepted>
<ce:abstract>
<ce:section-title>Abstract</ce:section-title>
<ce:abstract-sec>
<ce:simple-para>In many species, graft survival and graft-derived behavioral recovery are affected by the embryonic donor age. We compared the ability of solid and suspension grafts of human embryonic mesencephalic dopaminergic (DA) neurons at different embryonic stages to survive intraparenchymal transplantation into 6-OHDA lesioned immunosuppressed rats. Suspension grafts survived best when donor age was between postconception (PC) days 34 and 56. Transplants displayed numerous healthy tyrosine hydroxylase immunoreactive (TH-IR) neurons which sent extensive neuritic processes into the host striatum. Suspension grafts survived poorly when donor age was greater than 65 days. Solid implants displayed comparable viability of TH-IR neurons when donor age was between 44 and 65 days. No solid grafts contained TH-IR cells when donor tissue was older than 72 days. The suspension and solid methods of transplantation resulted in comparable survival of robust grafts, but solid grafts resulted in more intergraft variability than suspension grafts, particularly among the more marginal implants. Our results demonstrate that the upper limit for survival of human embryonic DA suspension grafts correlates well with the period of development of the human nigrostriatal pathway. The “window” for donor age of solid human embryonic DA grafts appears to be extended by about 9 days in comparison to suspension grafts. These data suggest that the upper age limit for grafting human mesencephalic DA neurons should be PC day 56 for suspension grafts, and PC day 65 for solid implants. Older donors are likely to produce grafts with fewer surviving DA neurons.</ce:simple-para>
</ce:abstract-sec>
</ce:abstract>
<ce:keywords>
<ce:section-title>Keywords</ce:section-title>
<ce:keyword>
<ce:text>Parkinson's disease</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Transplant</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Fetal</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Dopamine</ce:text>
</ce:keyword>
<ce:keyword>
<ce:text>Nigra</ce:text>
</ce:keyword>
</ce:keywords>
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<title>The influence of donor age on the survival of solid and suspension intraparenchymal human embryonic nigral grafts</title>
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<title>The influence of donor age on the survival of solid and suspension intraparenchymal human embryonic nigral grafts</title>
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<name type="personal">
<namePart type="given">Thomas B.</namePart>
<namePart type="family">Freeman</namePart>
<affiliation>Division of Neurosurgery, University of South Florida, Columbia Drive, Suite 730, Tampa, FL 33606, USA</affiliation>
<description>To whom correspondence should be addressed.</description>
<role>
<roleTerm type="text">author</roleTerm>
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</name>
<name type="personal">
<namePart type="given">Paul R.</namePart>
<namePart type="family">Sanberg</namePart>
<affiliation>Division of Neurosurgery, University of South Florida, Columbia Drive, Suite 730, Tampa, FL 33606, USA</affiliation>
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<name type="personal">
<namePart type="given">G.Michael</namePart>
<namePart type="family">Nauert</namePart>
<affiliation>Woman's Center, Tampa, FL, USA</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Barbara D.</namePart>
<namePart type="family">Boss</namePart>
<affiliation>Hana Biologics, Inc., Alameda, CA, USA</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
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<name type="personal">
<namePart type="given">Dennis</namePart>
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<affiliation>Hana Biologics, Inc., Alameda, CA, USA</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">C.Warren</namePart>
<namePart type="family">Olanow</namePart>
<affiliation>Department of Neurology, Mount Sinai Medical Center, New York, NY, USA</affiliation>
<role>
<roleTerm type="text">author</roleTerm>
</role>
</name>
<name type="personal">
<namePart type="given">Jeffrey H.</namePart>
<namePart type="family">Kordower</namePart>
<affiliation>Department of Neurological Sciences, Rush Presbyterian Medical Center, Chicago, IL, USA</affiliation>
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<abstract lang="en">In many species, graft survival and graft-derived behavioral recovery are affected by the embryonic donor age. We compared the ability of solid and suspension grafts of human embryonic mesencephalic dopaminergic (DA) neurons at different embryonic stages to survive intraparenchymal transplantation into 6-OHDA lesioned immunosuppressed rats. Suspension grafts survived best when donor age was between postconception (PC) days 34 and 56. Transplants displayed numerous healthy tyrosine hydroxylase immunoreactive (TH-IR) neurons which sent extensive neuritic processes into the host striatum. Suspension grafts survived poorly when donor age was greater than 65 days. Solid implants displayed comparable viability of TH-IR neurons when donor age was between 44 and 65 days. No solid grafts contained TH-IR cells when donor tissue was older than 72 days. The suspension and solid methods of transplantation resulted in comparable survival of robust grafts, but solid grafts resulted in more intergraft variability than suspension grafts, particularly among the more marginal implants. Our results demonstrate that the upper limit for survival of human embryonic DA suspension grafts correlates well with the period of development of the human nigrostriatal pathway. The “window” for donor age of solid human embryonic DA grafts appears to be extended by about 9 days in comparison to suspension grafts. These data suggest that the upper age limit for grafting human mesencephalic DA neurons should be PC day 56 for suspension grafts, and PC day 65 for solid implants. Older donors are likely to produce grafts with fewer surviving DA neurons.</abstract>
<note type="content">Section title: Original contribution</note>
<subject>
<genre>Keywords</genre>
<topic>Parkinson's disease</topic>
<topic>Transplant</topic>
<topic>Fetal</topic>
<topic>Dopamine</topic>
<topic>Nigra</topic>
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<genre type="Journal">journal</genre>
<originInfo>
<dateIssued encoding="w3cdtf">199501</dateIssued>
</originInfo>
<identifier type="ISSN">0963-6897</identifier>
<identifier type="PII">S0963-6897(00)X0012-7</identifier>
<part>
<date>199501</date>
<detail type="issue">
<title>Neural Transplantation into the CNS</title>
</detail>
<detail type="volume">
<number>4</number>
<caption>vol.</caption>
</detail>
<detail type="issue">
<number>1</number>
<caption>no.</caption>
</detail>
<extent unit="issue pages">
<start>1</start>
<end>154</end>
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<extent unit="pages">
<start>141</start>
<end>154</end>
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<identifier type="DOI">10.1016/0963-6897(94)00048-O</identifier>
<identifier type="PII">0963-6897(94)00048-O</identifier>
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