<?xml version="1.0" encoding="UTF-8"?><?xml-stylesheet type="text/xsl" href="static/style.xsl"?><OAI-PMH xmlns="http://www.openarchives.org/OAI/2.0/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/ http://www.openarchives.org/OAI/2.0/OAI-PMH.xsd"><responseDate>2026-06-14T10:38:29Z</responseDate><request verb="GetRecord" identifier="oai:repisalud.isciii.es:20.500.12105/19036" metadataPrefix="mets">https://repisalud.isciii.es/rest/oai/request</request><GetRecord><record><header><identifier>oai:repisalud.isciii.es:20.500.12105/19036</identifier><datestamp>2024-09-28T03:16:17Z</datestamp><setSpec>com_20.500.12105_2052</setSpec><setSpec>com_20.500.12105_2051</setSpec><setSpec>col_20.500.12105_19617</setSpec></header><metadata><mets xmlns="http://www.loc.gov/METS/" xmlns:doc="http://www.lyncode.com/xoai" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" ID="&#xa;&#x9;&#x9;&#x9;&#x9;DSpace_ITEM_20.500.12105-19036" TYPE="DSpace ITEM" PROFILE="DSpace METS SIP Profile 1.0" xsi:schemaLocation="http://www.loc.gov/METS/ http://www.loc.gov/standards/mets/mets.xsd" OBJID="&#xa;&#x9;&#x9;&#x9;&#x9;hdl:20.500.12105/19036">
   <metsHdr CREATEDATE="2026-06-14T12:38:29Z">
      <agent ROLE="CUSTODIAN" TYPE="ORGANIZATION">
         <name>Repisalud</name>
      </agent>
   </metsHdr>
   <dmdSec ID="DMD_20.500.12105_19036">
      <mdWrap MDTYPE="MODS">
         <xmlData xmlns:mods="http://www.loc.gov/mods/v3" xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-1.xsd">
            <mods:mods xsi:schemaLocation="http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-1.xsd">
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">author</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>González-Sastre, Rosa</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">author</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Coronel Lopez, Raquel</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">author</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Bernabeu-Zornoza, Adela</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">author</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Mateos-Martínez, Patricia</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">author</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Rosca, Andreea</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">author</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>López-Alonso, Victoria</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">author</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Liste-Noya, Isabel</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">funder</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Agencia Estatal de Investigación (España)</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">funder</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Ministerio de Ciencia e Innovación (España)</mods:namePart>
               </mods:name>
               <mods:name>
                  <mods:role>
                     <mods:roleTerm type="text">funder</mods:roleTerm>
                  </mods:role>
                  <mods:namePart>Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)</mods:namePart>
               </mods:name>
               <mods:extension>
                  <mods:dateAccessioned encoding="iso8601">2024-03-21T14:27:31Z</mods:dateAccessioned>
               </mods:extension>
               <mods:extension>
                  <mods:dateAvailable encoding="iso8601">2024-03-21T14:27:31Z</mods:dateAvailable>
               </mods:extension>
               <mods:originInfo>
                  <mods:dateIssued encoding="iso8601">2024-02</mods:dateIssued>
               </mods:originInfo>
               <mods:identifier type="citation">J Tissue Eng. 2024 Feb 9:15:20417314231226027.</mods:identifier>
               <mods:identifier type="doi">10.1177/20417314231226027</mods:identifier>
               <mods:identifier type="issn">2041-7314</mods:identifier>
               <mods:identifier type="journal">Journal of tissue engineering</mods:identifier>
               <mods:identifier type="pubmedID">38343770</mods:identifier>
               <mods:identifier type="uri">http://hdl.handle.net/20.500.12105/19036</mods:identifier>
               <mods:abstract>Human cerebral organoids (hCOs) offer the possibility of deepening the knowledge of human brain development, as well as the pathologies that affect it. The method developed here describes the efficient generation of hCOs by going directly from two-dimensional (2D) pluripotent stem cell (PSC) cultures to three-dimensional (3D) neuroepithelial tissue, avoiding dissociation and aggregation steps. This has been achieved by subjecting 2D cultures, from the beginning of the neural induction step, to dual-SMAD inhibition in combination with CHIR99021. This is a simple and reproducible protocol in which the hCOs generated develop properly presenting proliferative ventricular zones (VZs) formed by neural precursor and radial glia (RG) that differentiate to give rise to mature neurons and glial cells. The hCOs present additional cell types such as oligodendrocyte precursors, astrocytes, microglia-like cells, and endothelial-like cells. This new approach could help to overcome some of the existing limitations in the field of organoid biotechnology, facilitating its execution in any laboratory setting.</mods:abstract>
               <mods:language>
                  <mods:languageTerm authority="rfc3066">eng</mods:languageTerm>
               </mods:language>
               <mods:accessCondition type="useAndReproduction"/>
               <mods:subject>
                  <mods:topic>Human cerebral organoid</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Pluripotent stem cells</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Embryonic stem cells</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Neuroepithelium</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Ventricular zones</mods:topic>
               </mods:subject>
               <mods:subject>
                  <mods:topic>Embryoid  body</mods:topic>
               </mods:subject>
               <mods:titleInfo>
                  <mods:title>Efficient generation of human cerebral organoids directly from adherent cultures of pluripotent stem cells</mods:title>
               </mods:titleInfo>
               <mods:genre>research article</mods:genre>
            </mods:mods>
         </xmlData>
      </mdWrap>
   </dmdSec>
   <amdSec ID="TMD_20.500.12105_19036">
      <rightsMD ID="RIG_20.500.12105_19036">
         <mdWrap MIMETYPE="text/plain" MDTYPE="OTHER" OTHERMDTYPE="DSpaceDepositLicense">
            <binData>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</binData>
         </mdWrap>
      </rightsMD>
   </amdSec>
   <amdSec ID="FO_20.500.12105_19036_1">
      <techMD ID="TECH_O_20.500.12105_19036_1">
         <mdWrap MDTYPE="PREMIS">
            <xmlData xmlns:premis="http://www.loc.gov/standards/premis" xsi:schemaLocation="http://www.loc.gov/standards/premis http://www.loc.gov/standards/premis/PREMIS-v1-0.xsd">
               <premis:premis>
                  <premis:object>
                     <premis:objectIdentifier>
                        <premis:objectIdentifierType>URL</premis:objectIdentifierType>
                        <premis:objectIdentifierValue>https://repisalud.isciii.es/bitstreams/4a3a6c5b-5348-4435-a454-9c4498dff487/download</premis:objectIdentifierValue>
                     </premis:objectIdentifier>
                     <premis:objectCategory>File</premis:objectCategory>
                     <premis:objectCharacteristics>
                        <premis:fixity>
                           <premis:messageDigestAlgorithm>MD5</premis:messageDigestAlgorithm>
                           <premis:messageDigest>201ddd16e5f67cc3d11c233448e2aed2</premis:messageDigest>
                        </premis:fixity>
                        <premis:size>5013604</premis:size>
                        <premis:format>
                           <premis:formatDesignation>
                              <premis:formatName>application/pdf</premis:formatName>
                           </premis:formatDesignation>
                        </premis:format>
                     </premis:objectCharacteristics>
                     <premis:originalName>EfficientGenerationHumanCerebralOrganoids_2024.pdf</premis:originalName>
                  </premis:object>
               </premis:premis>
            </xmlData>
         </mdWrap>
      </techMD>
   </amdSec>
   <amdSec ID="FT_20.500.12105_19036_4">
      <techMD ID="TECH_T_20.500.12105_19036_4">
         <mdWrap MDTYPE="PREMIS">
            <xmlData xmlns:premis="http://www.loc.gov/standards/premis" xsi:schemaLocation="http://www.loc.gov/standards/premis http://www.loc.gov/standards/premis/PREMIS-v1-0.xsd">
               <premis:premis>
                  <premis:object>
                     <premis:objectIdentifier>
                        <premis:objectIdentifierType>URL</premis:objectIdentifierType>
                        <premis:objectIdentifierValue>https://repisalud.isciii.es/bitstreams/2b6c7208-518a-4ac4-9429-d1aea217bf7d/download</premis:objectIdentifierValue>
                     </premis:objectIdentifier>
                     <premis:objectCategory>File</premis:objectCategory>
                     <premis:objectCharacteristics>
                        <premis:fixity>
                           <premis:messageDigestAlgorithm>MD5</premis:messageDigestAlgorithm>
                           <premis:messageDigest>dc3066cf3a3883f2109cc298fe44d317</premis:messageDigest>
                        </premis:fixity>
                        <premis:size>55223</premis:size>
                        <premis:format>
                           <premis:formatDesignation>
                              <premis:formatName>text/plain</premis:formatName>
                           </premis:formatDesignation>
                        </premis:format>
                     </premis:objectCharacteristics>
                     <premis:originalName>EfficientGenerationHumanCerebralOrganoids_2024.pdf.txt</premis:originalName>
                  </premis:object>
               </premis:premis>
            </xmlData>
         </mdWrap>
      </techMD>
   </amdSec>
   <fileSec>
      <fileGrp USE="ORIGINAL">
         <file ID="BITSTREAM_ORIGINAL_20.500.12105_19036_1" MIMETYPE="application/pdf" SEQ="1" SIZE="5013604" CHECKSUM="201ddd16e5f67cc3d11c233448e2aed2" CHECKSUMTYPE="MD5" ADMID="FO_20.500.12105_19036_1" GROUPID="GROUP_BITSTREAM_20.500.12105_19036_1">
            <FLocat LOCTYPE="URL" xlink:type="simple" xlink:href="https://repisalud.isciii.es/bitstreams/4a3a6c5b-5348-4435-a454-9c4498dff487/download"/>
         </file>
      </fileGrp>
      <fileGrp USE="TEXT">
         <file ID="BITSTREAM_TEXT_20.500.12105_19036_4" MIMETYPE="text/plain" SEQ="4" SIZE="55223" CHECKSUM="dc3066cf3a3883f2109cc298fe44d317" CHECKSUMTYPE="MD5" ADMID="FT_20.500.12105_19036_4" GROUPID="GROUP_BITSTREAM_20.500.12105_19036_4">
            <FLocat LOCTYPE="URL" xlink:type="simple" xlink:href="https://repisalud.isciii.es/bitstreams/2b6c7208-518a-4ac4-9429-d1aea217bf7d/download"/>
         </file>
      </fileGrp>
   </fileSec>
   <structMap LABEL="DSpace Object" TYPE="LOGICAL">
      <div TYPE="DSpace Object Contents" ADMID="DMD_20.500.12105_19036">
         <div TYPE="DSpace BITSTREAM">
            <fptr FILEID="BITSTREAM_ORIGINAL_20.500.12105_19036_1"/>
         </div>
      </div>
   </structMap>
</mets></metadata></record></GetRecord></OAI-PMH>