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Title: Morphogen Delivery by Osteoconductive Nanoparticles Instructs Stromal Cell Spheroid Phenotype
Abstract

Mesenchymal stem/stromal cells (MSCs) exhibit a rapid loss in osteogenic phenotype upon removal of osteoinductive cues, as commonly occurs during transplantation. Osteogenic differentiation can be more effectively but not fully maintained by aggregating MSCs into spheroids. Therefore, the development of effective strategies that prolong the efficacy of inductive growth factors would be advantageous for advancing cell‐based therapies. To address this challenge, osteoinductive bone morphogenetic protein‐2 (BMP‐2) is adsorbed to osteoconductive hydroxyapatite (HA) nanoparticles for incorporation into MSC spheroids. MSC induction is evaluated in osteogenic conditions and retention of the osteogenic phenotype in the absence of other osteogenic cues. HA is more uniformly incorporated into spheroids at lower concentrations, while BMP‐2 dosage is dependent upon initial morphogen concentration. MSC spheroids containing BMP‐2‐loaded HA nanoparticles exhibit greater alkaline phosphatase activity and more uniform spatial expression of osteocalcin compared to spheroids with uncoated HA nanoparticles. Spheroids cultured in media containing soluble BMP‐2 demonstrate differentiation only at the spheroid periphery. Furthermore, the osteogenic phenotype of MSC spheroids is better retained with BMP‐2‐laden HA upon the removal of soluble osteogenic cues. These findings represent a promising strategy for simultaneous delivery of osteoconductive and osteoinductive signals for enhancing MSC participation in bone formation.

 
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NSF-PAR ID:
10460320
Author(s) / Creator(s):
 ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Advanced Biosystems
Volume:
3
Issue:
12
ISSN:
2366-7478
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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    </sec> </div> <a href='#' class='show open-abstract' style='margin-left:10px;'>more »</a> <a href='#' class='hide close-abstract' style='margin-left:10px;'>« less</a> </div><div class="clearfix"></div> </div> </li> </ol> <div class="push_top"></div> </div> </div> <div class="col-md-3"> <div id="citation-sidebar"> <ul class="nav nav-list" id="citation-fulltext-sidebar" style="font-size: 14px; font-family: Georgia Regular;"> <li class="divider"></li> <li style="font-weight: bold;font-size:13px;">Journal Article:</li> <li style="word-break:break-all" class="small"> <a href="https://doi.org/10.1002/adbi.201900141" target="_blank" rel="noopener noreferrer" title="Document DOI URL" class="external-link" data-ostiid="10460320" style="word-wrap: break-word;">https://doi.org/10.1002/adbi.201900141  <span class="fas fa-external-link-alt"></span></a></li> </ul> <div class="hidden-print"> <ul class="nav nav-list clearfix" id="sidebar-feedback" style="margin-top: 20px; margin-bottom: 20px; clear: both;"> <li style="position: relative;"> <div class="feedback-container"> <div style="font-family: Georgia Regular; font-size: 14px; color: #313b52; padding:20px;"> Have feedback or suggestions for a way to improve these results?<br/> <span style="text-decoration: underline;"> <script type="text/javascript" defer>/* <![CDATA[ */ user = "feedback"; site = "research.gov"; subject = "?subject=Comments or Suggestions"; content = "<span class='far fa-envelope'></span><span class='span-link' style='padding-left:5px'>Let us know</span>"; id = ""; document.write('<a itemprop="'+ id +'" href="mailto:' + user + '@' + site + subject + '">' + (content != '' ? content : (user + '@' + site)) + '</a>'); /* ]]> */</script> <noscript></noscript>!</span> </div> </li> </ul> <ul class="nav nav-list" style="font-size: 14px; font-family: Arial Regular;"> <li class="nav-header header-format">Citation Formats</li> <li class="links-format"><a href="#cite-mla" data-toggle="modal">MLA</a> <div id="cite-mla" class="modal" tabindex="-1" role="dialog" aria-labelledby="cite-mla_label" aria-hidden="true"> <div class="modal-dialog"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-hidden="true">×</button> <strong id="cite-mla_label">Cite: MLA Format</strong> </div> <div class="modal-body" >Whitehead, Jacklyn, Kothambawala, Alefia, and Kent Leach, J. <em>Morphogen Delivery by Osteoconductive Nanoparticles Instructs Stromal Cell Spheroid Phenotype</em>. <em>Advanced Biosystems</em> 3.12 Web. doi:10.1002/adbi.201900141. </div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="links-format"><a href="#cite-apa" data-toggle="modal">APA</a> <div id="cite-apa" class="modal" tabindex="-1" role="dialog" aria-labelledby="cite-apa_label" aria-hidden="true"> <div class="modal-dialog"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-hidden="true">×</button> <strong id="cite-apa_label">Cite: APA Format</strong> </div> <div class="modal-body">Whitehead, Jacklyn, Kothambawala, Alefia, & Kent Leach, J. <em>Morphogen Delivery by Osteoconductive Nanoparticles Instructs Stromal Cell Spheroid Phenotype</em>. <em>Advanced Biosystems</em>, <em>3</em> (12). <a href="https://doi.org/10.1002/adbi.201900141">https://doi.org/10.1002/adbi.201900141</a> </div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="links-format"><a href="#cite-chi" data-toggle="modal">Chicago</a> <div id="cite-chi" class="modal" tabindex="-1" role="dialog" aria-labelledby="cite-chi_label" aria-hidden="true"> <div class="modal-dialog"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-hidden="true">×</button> <strong id="cite-chi_label">Cite: Chicago Format</strong> </div> <div class="modal-body">Whitehead, Jacklyn, Kothambawala, Alefia, and Kent Leach, J. "Morphogen Delivery by Osteoconductive Nanoparticles Instructs Stromal Cell Spheroid Phenotype". <em>Advanced Biosystems</em> 3 (12). Country unknown/Code not available: Wiley Blackwell (John Wiley & Sons). <a href="https://doi.org/10.1002/adbi.201900141">https://doi.org/10.1002/adbi.201900141.</a> <a href="https://par.nsf.gov/biblio/10460320">https://par.nsf.gov/biblio/10460320</a>. </div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="links-format"><a href="#cite-bib" data-toggle="modal">BibTeX</a> <div id="cite-bib" class="modal" tabindex="-1" role="dialog" aria-labelledby="cite-bib_label" aria-hidden="true"> <div class="modal-dialog"> <div class="modal-content"> <div class="modal-header"> <button type="button" class="close" data-dismiss="modal" aria-hidden="true">×</button> <strong id="cite-bib_label">Cite: BibTeX Format</strong> </div> <div class="modal-body"> @article{osti_10460320,<br/> place = {Country unknown/Code not available}, title = {Morphogen Delivery by Osteoconductive Nanoparticles Instructs Stromal Cell Spheroid Phenotype}, url = {https://par.nsf.gov/biblio/10460320}, DOI = {10.1002/adbi.201900141}, abstractNote = {Abstract Mesenchymal stem/stromal cells (MSCs) exhibit a rapid loss in osteogenic phenotype upon removal of osteoinductive cues, as commonly occurs during transplantation. Osteogenic differentiation can be more effectively but not fully maintained by aggregating MSCs into spheroids. Therefore, the development of effective strategies that prolong the efficacy of inductive growth factors would be advantageous for advancing cell‐based therapies. To address this challenge, osteoinductive bone morphogenetic protein‐2 (BMP‐2) is adsorbed to osteoconductive hydroxyapatite (HA) nanoparticles for incorporation into MSC spheroids. MSC induction is evaluated in osteogenic conditions and retention of the osteogenic phenotype in the absence of other osteogenic cues. HA is more uniformly incorporated into spheroids at lower concentrations, while BMP‐2 dosage is dependent upon initial morphogen concentration. MSC spheroids containing BMP‐2‐loaded HA nanoparticles exhibit greater alkaline phosphatase activity and more uniform spatial expression of osteocalcin compared to spheroids with uncoated HA nanoparticles. Spheroids cultured in media containing soluble BMP‐2 demonstrate differentiation only at the spheroid periphery. Furthermore, the osteogenic phenotype of MSC spheroids is better retained with BMP‐2‐laden HA upon the removal of soluble osteogenic cues. These findings represent a promising strategy for simultaneous delivery of osteoconductive and osteoinductive signals for enhancing MSC participation in bone formation.}, journal = {Advanced Biosystems}, volume = {3}, number = {12}, publisher = {Wiley Blackwell (John Wiley & Sons)}, author = {Whitehead, Jacklyn and Kothambawala, Alefia and Kent Leach, J.}, }</div> <div class="modal-footer"> <button class="btn btn-sm btn-default" data-dismiss="modal" aria-hidden="true">Close</button> </div> </div> </div> </div></li> <li class="divider"></li> </ul> <ul class="nav nav-list" style="font-size: 14px; font-family: Arial Regular;"> <li class="nav-header header-format">Export Metadata</li> <li class="links-format"><a href="https://par.nsf.gov/endnote?osti_id=10460320">EndNote</a></li> <li class="links-format"><a href="https://par.nsf.gov/export/format:excel/osti-id:10460320">Excel</a></li> <li class="links-format"><a href="https://par.nsf.gov/export/format:csv/osti-id:10460320">CSV</a></li> <li class="links-format"><a href="https://par.nsf.gov/export/format:xml/osti-id:10460320">XML</a></li> <li class="divider"></li> </ul> <ul class="nav nav-list" style="font-size: 14px; 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