Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis.
Identifieur interne : 000047 ( Main/Exploration ); précédent : 000046; suivant : 000048Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis.
Auteurs : Rachel M. Wise [États-Unis] ; Mark A A. Harrison [États-Unis] ; Brianne N. Sullivan [États-Unis] ; Sara Al-Ghadban [États-Unis] ; Sarah J. Aleman [États-Unis] ; Amber T. Vinluan [États-Unis] ; Emily R. Monaco [États-Unis] ; Umberto M. Donato [États-Unis] ; India A. Pursell [États-Unis] ; Bruce A. Bunnell [États-Unis]Source :
- Cells [ 2073-4409 ] ; 2020.
Abstract
Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4+ T helper (Th) and T regulatory (Treg) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less Th and Treg cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.
DOI: 10.3390/cells9102218
PubMed: 33008073
PubMed Central: PMC7600854
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Wise</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Harrison, Mark A A" sort="Harrison, Mark A A" uniqKey="Harrison M" first="Mark A A" last="Harrison">Mark A A. 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Wise</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Harrison, Mark A A" sort="Harrison, Mark A A" uniqKey="Harrison M" first="Mark A A" last="Harrison">Mark A A. Harrison</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Sullivan, Brianne N" sort="Sullivan, Brianne N" uniqKey="Sullivan B" first="Brianne N" last="Sullivan">Brianne N. Sullivan</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Al Ghadban, Sara" sort="Al Ghadban, Sara" uniqKey="Al Ghadban S" first="Sara" last="Al-Ghadban">Sara Al-Ghadban</name><affiliation wicri:level="2"><nlm:affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Aleman, Sarah J" sort="Aleman, Sarah J" uniqKey="Aleman S" first="Sarah J" last="Aleman">Sarah J. Aleman</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Vinluan, Amber T" sort="Vinluan, Amber T" uniqKey="Vinluan A" first="Amber T" last="Vinluan">Amber T. Vinluan</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Monaco, Emily R" sort="Monaco, Emily R" uniqKey="Monaco E" first="Emily R" last="Monaco">Emily R. Monaco</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Donato, Umberto M" sort="Donato, Umberto M" uniqKey="Donato U" first="Umberto M" last="Donato">Umberto M. Donato</name><affiliation wicri:level="2"><nlm:affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Pursell, India A" sort="Pursell, India A" uniqKey="Pursell I" first="India A" last="Pursell">India A. Pursell</name><affiliation wicri:level="2"><nlm:affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author><author><name sortKey="Bunnell, Bruce A" sort="Bunnell, Bruce A" uniqKey="Bunnell B" first="Bruce A" last="Bunnell">Bruce A. Bunnell</name><affiliation wicri:level="2"><nlm:affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107</wicri:regionArea><placeName><region type="state">Texas</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112</wicri:regionArea><placeName><region type="state">Louisiane</region></placeName></affiliation></author></analytic><series><title level="j">Cells</title><idno type="eISSN">2073-4409</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4<sup>+</sup> T helper (T<sub>h</sub>) and T regulatory (T<sub>reg</sub>) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less T<sub>h</sub> and T<sub>reg</sub> cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">33008073</PMID><DateRevised><Year>2020</Year><Month>11</Month><Day>03</Day></DateRevised><Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2073-4409</ISSN><JournalIssue CitedMedium="Internet"><Volume>9</Volume><Issue>10</Issue><PubDate><Year>2020</Year><Month>Sep</Month><Day>30</Day></PubDate></JournalIssue><Title>Cells</Title><ISOAbbreviation>Cells</ISOAbbreviation></Journal><ArticleTitle>Short-Term Rapamycin Preconditioning Diminishes Therapeutic Efficacy of Human Adipose-Derived Stem Cells in a Murine Model of Multiple Sclerosis.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">E2218</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.3390/cells9102218</ELocationID><Abstract><AbstractText>Human adipose-derived stem cells (ASCs) show immense promise for treating inflammatory diseases, attributed primarily to their potent paracrine signaling. Previous investigations demonstrated that short-term Rapamycin preconditioning of bone marrow-derived stem cells (BMSCs) elevated secretion of prostaglandin E2, a pleiotropic molecule with therapeutic effects in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS), and enhanced immunosuppressive capacity in vitro. However, this has yet to be examined in ASCs. The present study examined the therapeutic potential of short-term Rapamycin-preconditioned ASCs in the EAE model. Animals were treated at peak disease with control ASCs (EAE-ASCs), Rapa-preconditioned ASCs (EAE-Rapa-ASCs), or vehicle control (EAE). Results show that EAE-ASCs improved clinical disease scores and elevated intact myelin compared to both EAE and EAE-Rapa-ASC animals. These results correlated with augmented CD4<sup>+</sup> T helper (T<sub>h</sub>) and T regulatory (T<sub>reg</sub>) cell populations in the spinal cord, and increased gene expression of interleukin-10 (IL-10), an anti-inflammatory cytokine. Conversely, EAE-Rapa-ASC mice showed no improvement in clinical disease scores, reduced myelin levels, and significantly less T<sub>h</sub> and T<sub>reg</sub> cells in the spinal cord. These findings suggest that short-term Rapamycin preconditioning reduces the therapeutic efficacy of ASCs when applied to late-stage EAE.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Wise</LastName><ForeName>Rachel M</ForeName><Initials>RM</Initials><AffiliationInfo><Affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Harrison</LastName><ForeName>Mark A A</ForeName><Initials>MAA</Initials><Identifier Source="ORCID">0000-0003-4685-3757</Identifier><AffiliationInfo><Affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sullivan</LastName><ForeName>Brianne N</ForeName><Initials>BN</Initials><AffiliationInfo><Affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Al-Ghadban</LastName><ForeName>Sara</ForeName><Initials>S</Initials><Identifier Source="ORCID">0000-0001-8544-5751</Identifier><AffiliationInfo><Affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aleman</LastName><ForeName>Sarah J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vinluan</LastName><ForeName>Amber T</ForeName><Initials>AT</Initials><AffiliationInfo><Affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Monaco</LastName><ForeName>Emily R</ForeName><Initials>ER</Initials><AffiliationInfo><Affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Donato</LastName><ForeName>Umberto M</ForeName><Initials>UM</Initials><AffiliationInfo><Affiliation>Neuroscience Program, Tulane Brain Institute, Tulane University School of Science & Engineering, New Orleans, LA 70118, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Pursell</LastName><ForeName>India A</ForeName><Initials>IA</Initials><Identifier Source="ORCID">0000-0002-7207-3589</Identifier><AffiliationInfo><Affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bunnell</LastName><ForeName>Bruce A</ForeName><Initials>BA</Initials><AffiliationInfo><Affiliation>Center for Stem Cell Research & Regenerative Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2020</Year><Month>09</Month><Day>30</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Cells</MedlineTA><NlmUniqueID>101600052</NlmUniqueID><ISSNLinking>2073-4409</ISSNLinking></MedlineJournalInfo><CitationSubset>IM</CitationSubset><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">Rapamycin</Keyword><Keyword MajorTopicYN="N">adipose tissue-derived stem cells 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