Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment
An attractive option for tissue engineering is to use of multicellular spheroids as microtissues, particularly with stem cell spheroids. Conventional approaches of fabricating spheroids suffer from low throughput and polydispersity in size and fail to supplement cues from extracellular matrix (ECM)...
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| Veröffentlicht in: | Scientific reports 2013-12, Vol.3 (1), p.3462-3462, Article 3462 |
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| creator | Chan, Hon Fai Zhang, Ying Ho, Yi-Ping Chiu, Ya-Ling Jung, Youngmee Leong, Kam W. |
| description | An attractive option for tissue engineering is to use of multicellular spheroids as microtissues, particularly with stem cell spheroids. Conventional approaches of fabricating spheroids suffer from low throughput and polydispersity in size and fail to supplement cues from extracellular matrix (ECM) for enhanced differentiation. In this study, we report the application of microfluidics-generated water-in-oil-in-water (w/o/w) double-emulsion (DE) droplets as pico-liter sized bioreactor for rapid cell assembly and well-controlled microenvironment for spheroid culture. Cells aggregated to form size-controllable (30–80 μm) spheroids in DE droplets within 150 min and could be retrieved via a droplet-releasing agent. Moreover, precursor hydrogel solution can be adopted as the inner phase to produce spheroid-encapsulated microgels after spheroid formation. As an example, the encapsulation of human mesenchymal stem cells (hMSC) spheroids in alginate and alginate-arginine-glycine-aspartic acid (-RGD) microgel was demonstrated, with enhanced osteogenic differentiation further exhibited in the latter case. |
| doi_str_mv | 10.1038/srep03462 |
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Conventional approaches of fabricating spheroids suffer from low throughput and polydispersity in size and fail to supplement cues from extracellular matrix (ECM) for enhanced differentiation. In this study, we report the application of microfluidics-generated water-in-oil-in-water (w/o/w) double-emulsion (DE) droplets as pico-liter sized bioreactor for rapid cell assembly and well-controlled microenvironment for spheroid culture. Cells aggregated to form size-controllable (30–80 μm) spheroids in DE droplets within 150 min and could be retrieved via a droplet-releasing agent. Moreover, precursor hydrogel solution can be adopted as the inner phase to produce spheroid-encapsulated microgels after spheroid formation. As an example, the encapsulation of human mesenchymal stem cells (hMSC) spheroids in alginate and alginate-arginine-glycine-aspartic acid (-RGD) microgel was demonstrated, with enhanced osteogenic differentiation further exhibited in the latter case.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep03462</identifier><identifier>PMID: 24322507</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 13/107 ; 13/62 ; 631/1647/277 ; 631/532/2074 ; 631/61/2035 ; 631/61/54/2295 ; Alginic acid ; Arginine ; Aspartic acid ; Biomedical materials ; Bioreactors ; Cell culture ; Cell Culture Techniques ; Emulsions ; Emulsions - chemistry ; Encapsulation ; Extracellular Matrix ; Glycine ; Humanities and Social Sciences ; Humans ; Hydrogels ; Mesenchymal Stromal Cells ; Mesenchyme ; Microfluidic Analytical Techniques ; Microfluidics ; Molecular weight ; multidisciplinary ; Oil ; Permeability ; Science ; Spheroids ; Spheroids, Cellular ; Stem cells ; Tissue Engineering</subject><ispartof>Scientific reports, 2013-12, Vol.3 (1), p.3462-3462, Article 3462</ispartof><rights>The Author(s) 2013</rights><rights>Copyright Nature Publishing Group Dec 2013</rights><rights>Copyright © 2013, Macmillan Publishers Limited. All rights reserved 2013 Macmillan Publishers Limited. All rights reserved</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-dc89e14a5539e4fe13ca3f567e4690e406bafd13b487b7c7f6fefbf8d0510c453</citedby><cites>FETCH-LOGICAL-c438t-dc89e14a5539e4fe13ca3f567e4690e406bafd13b487b7c7f6fefbf8d0510c453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857570/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857570/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24322507$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, Hon Fai</creatorcontrib><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Ho, Yi-Ping</creatorcontrib><creatorcontrib>Chiu, Ya-Ling</creatorcontrib><creatorcontrib>Jung, Youngmee</creatorcontrib><creatorcontrib>Leong, Kam W.</creatorcontrib><title>Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>An attractive option for tissue engineering is to use of multicellular spheroids as microtissues, particularly with stem cell spheroids. Conventional approaches of fabricating spheroids suffer from low throughput and polydispersity in size and fail to supplement cues from extracellular matrix (ECM) for enhanced differentiation. In this study, we report the application of microfluidics-generated water-in-oil-in-water (w/o/w) double-emulsion (DE) droplets as pico-liter sized bioreactor for rapid cell assembly and well-controlled microenvironment for spheroid culture. Cells aggregated to form size-controllable (30–80 μm) spheroids in DE droplets within 150 min and could be retrieved via a droplet-releasing agent. Moreover, precursor hydrogel solution can be adopted as the inner phase to produce spheroid-encapsulated microgels after spheroid formation. 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Conventional approaches of fabricating spheroids suffer from low throughput and polydispersity in size and fail to supplement cues from extracellular matrix (ECM) for enhanced differentiation. In this study, we report the application of microfluidics-generated water-in-oil-in-water (w/o/w) double-emulsion (DE) droplets as pico-liter sized bioreactor for rapid cell assembly and well-controlled microenvironment for spheroid culture. Cells aggregated to form size-controllable (30–80 μm) spheroids in DE droplets within 150 min and could be retrieved via a droplet-releasing agent. Moreover, precursor hydrogel solution can be adopted as the inner phase to produce spheroid-encapsulated microgels after spheroid formation. As an example, the encapsulation of human mesenchymal stem cells (hMSC) spheroids in alginate and alginate-arginine-glycine-aspartic acid (-RGD) microgel was demonstrated, with enhanced osteogenic differentiation further exhibited in the latter case.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24322507</pmid><doi>10.1038/srep03462</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Springer Nature Open Access Journals; Full-Text Journals in Chemistry (Open access); DOAJ Directory of Open Access Journals; PubMed Central; EZB Electronic Journals Library; Nature出版集团开放获取期刊 |
| subjects | 13/100 13/107 13/62 631/1647/277 631/532/2074 631/61/2035 631/61/54/2295 Alginic acid Arginine Aspartic acid Biomedical materials Bioreactors Cell culture Cell Culture Techniques Emulsions Emulsions - chemistry Encapsulation Extracellular Matrix Glycine Humanities and Social Sciences Humans Hydrogels Mesenchymal Stromal Cells Mesenchyme Microfluidic Analytical Techniques Microfluidics Molecular weight multidisciplinary Oil Permeability Science Spheroids Spheroids, Cellular Stem cells Tissue Engineering |
| title | Rapid formation of multicellular spheroids in double-emulsion droplets with controllable microenvironment |
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