Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment
Abstract Background Cell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and...
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| Veröffentlicht in: | Biomaterials 2015-12, Vol.73, p.1-11 |
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| creator | Chan, Angel T Karakas, Mehmet F Vakrou, Styliani Afzal, Junaid Rittenbach, Andrew Lin, Xiaoping Wahl, Richard L Pomper, Martin G Steenbergen, Charles J Tsui, Benjamin M.W Elisseeff, Jennifer H Abraham, M. Roselle |
| description | Abstract Background Cell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and anoikis, which contribute to low engraftment. Objective We tissue engineered scaffolds with the goal of rapidly restoring metabolism, promoting viability, proliferation and engraftment of encapsulated stem cells. Methods The carboxyl groups of HA were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS) groups that react with free amine groups to form amide bonds. HA-NHS was cross-linked by serum to generate HA:Serum (HA:Ser) hydrogels. Physical properties of HA:Ser hydrogels were measured. Effect of encapsulating cardiosphere-derived cells (CDCs) in HA:Ser hydrogels on viability, proliferation, glucose uptake and metabolism was assessed in vitro. In vivo acute intra-myocardial cell retention of18 FDG-labeled CDCs encapsulated in HA:Ser hydrogels was quantified. Effect of CDC encapsulation in HA:Ser hydrogels on in vivo metabolism and engraftment at 7 days was assessed by serial, dual isotope SPECT-CT and bioluminescence imaging of CDCs expressing the Na-iodide symporter and firefly luciferase genes respectively. Effect of HA:Ser hydrogels ± CDCs on cardiac function was assessed at 7 days & 28 days post-infarct. Results HA:Ser hydrogels are highly bio-adhesive, biodegradable, promote rapid cell adhesion, glucose uptake and restore bioenergetics of encapsulated cells within 1 h of encapsulation, both in vitro and in vivo. These metabolic scaffolds can be applied epicardially as a patch to beating hearts or injected intramyocardially. HA:Ser hydrogels markedly increase acute intramyocardial retention (∼6 fold), promote in vivo viability, proliferation, engraftment of encapsulated stem cells and angiogenesis. Conclusion HA:Ser hydrogels serve as ‘synthetic stem cell niches’ that rapidly restore metabolism of encapsulated stem cells, promote stem cell engraftment and angiogenesis. These first ever, tissue engineered metabolic scaffolds hold promise for clinical translation in conjunction with CDCs and possibly other stem cell types. |
| doi_str_mv | 10.1016/j.biomaterials.2015.09.001 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4980097</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>1_s2_0_S0142961215007383</els_id><sourcerecordid>1762111541</sourcerecordid><originalsourceid>FETCH-LOGICAL-c641t-27f3439434d6c928533f50061a0bf501892e9e3a09db6e4a579cf3a408d04dc43</originalsourceid><addsrcrecordid>eNqNkk9v1DAQxSMEokvhK6CIE5eE8Z_EMYdKqAWKVIkDcLa89mTrJY4XO6mUb4-jLVXhwp5syW_ezPj9iuINgZoAad_t660LXk8YnR5STYE0NcgagDwpNqQTXdVIaJ4WGyCcVrIl9Kx4kdI-Czhw-rw4oy0TnRTtpvDXix7mGEZnSm2crRLG2Ze3i41hh0Mqoz44OyxlxDSFiKXHSW_D4JIvQ1_iaPQhzUMexpZpQl8aHHKVHm15iMGHCbNmF3U_eRynl8WzPo-Mr-7P8-LHp4_fL6-rm6-fv1x-uKlMy8lUUdEzziRn3LZG0q5hrG8AWqJhmy-kkxQlMg3SblvkuhHS9Exz6Cxwazg7Ly6Ovod569Ga3DrqQR2i8zouKmin_n4Z3a3ahTvFZQcgRTZ4e28Qw685r668S-tqesQwJ0UBgDZCAPuvlIiWEkIaTk6QUtHKnMwprpTmqBsis_T9UWpiSCli_7AnAbUCo_bqMTBqBUaBVJmHXPz68U89lP4hJAuujoIMA945jCoZl2NH6yKaSdngTutz8Y-NGVyGTg8_ccG0D3Mc1xqiElWgvq3oruSSnLtgHWO_Afew70Q</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1722187519</pqid></control><display><type>article</type><title>Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals Complete</source><creator>Chan, Angel T ; Karakas, Mehmet F ; Vakrou, Styliani ; Afzal, Junaid ; Rittenbach, Andrew ; Lin, Xiaoping ; Wahl, Richard L ; Pomper, Martin G ; Steenbergen, Charles J ; Tsui, Benjamin M.W ; Elisseeff, Jennifer H ; Abraham, M. Roselle</creator><creatorcontrib>Chan, Angel T ; Karakas, Mehmet F ; Vakrou, Styliani ; Afzal, Junaid ; Rittenbach, Andrew ; Lin, Xiaoping ; Wahl, Richard L ; Pomper, Martin G ; Steenbergen, Charles J ; Tsui, Benjamin M.W ; Elisseeff, Jennifer H ; Abraham, M. Roselle</creatorcontrib><description>Abstract Background Cell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and anoikis, which contribute to low engraftment. Objective We tissue engineered scaffolds with the goal of rapidly restoring metabolism, promoting viability, proliferation and engraftment of encapsulated stem cells. Methods The carboxyl groups of HA were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS) groups that react with free amine groups to form amide bonds. HA-NHS was cross-linked by serum to generate HA:Serum (HA:Ser) hydrogels. Physical properties of HA:Ser hydrogels were measured. Effect of encapsulating cardiosphere-derived cells (CDCs) in HA:Ser hydrogels on viability, proliferation, glucose uptake and metabolism was assessed in vitro. In vivo acute intra-myocardial cell retention of18 FDG-labeled CDCs encapsulated in HA:Ser hydrogels was quantified. Effect of CDC encapsulation in HA:Ser hydrogels on in vivo metabolism and engraftment at 7 days was assessed by serial, dual isotope SPECT-CT and bioluminescence imaging of CDCs expressing the Na-iodide symporter and firefly luciferase genes respectively. Effect of HA:Ser hydrogels ± CDCs on cardiac function was assessed at 7 days & 28 days post-infarct. Results HA:Ser hydrogels are highly bio-adhesive, biodegradable, promote rapid cell adhesion, glucose uptake and restore bioenergetics of encapsulated cells within 1 h of encapsulation, both in vitro and in vivo. These metabolic scaffolds can be applied epicardially as a patch to beating hearts or injected intramyocardially. HA:Ser hydrogels markedly increase acute intramyocardial retention (∼6 fold), promote in vivo viability, proliferation, engraftment of encapsulated stem cells and angiogenesis. Conclusion HA:Ser hydrogels serve as ‘synthetic stem cell niches’ that rapidly restore metabolism of encapsulated stem cells, promote stem cell engraftment and angiogenesis. These first ever, tissue engineered metabolic scaffolds hold promise for clinical translation in conjunction with CDCs and possibly other stem cell types.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2015.09.001</identifier><identifier>PMID: 26378976</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Advanced Basic Science ; Angiogenesis ; Animals ; Biocompatibility ; Biocompatible Materials - chemistry ; biodegradability ; bioluminescence ; Biomedical materials ; blood serum ; cardiac output ; Cell Adhesion ; Cell Proliferation ; Cell Survival ; Cell Transplantation ; crosslinking ; Dentistry ; dissociation ; Echocardiography ; Elastic Modulus ; Embryonic Stem Cells - cytology ; Encapsulation ; energy metabolism ; Engraftment ; Female ; Fluorodeoxyglucose F18 - chemistry ; genes ; glucose ; Glucose - chemistry ; HA:Serum hydrogels ; heart ; Heart - drug effects ; Heart - physiology ; Humans ; Hyaluronic Acid - chemistry ; hydrocolloids ; Hydrogels ; Hydrogels - chemistry ; image analysis ; in vitro studies ; In vivo testing ; Intercellular Signaling Peptides and Proteins - metabolism ; isotopes ; luciferase ; Male ; Mesenchymal Stromal Cells - cytology ; Metabolism ; Mice ; Molecular imaging ; Multimodal Imaging ; Myocardium - metabolism ; necrosis ; Neovascularization, Pathologic ; niches ; physical properties ; Rats ; Rats, Inbred WKY ; Stem Cell Transplantation - instrumentation ; Stem Cell Transplantation - methods ; Stem cells ; Stem Cells - cytology ; succinic acid ; Surgical implants ; symporters ; Tissue Engineering ; Tissue Scaffolds ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed ; viability</subject><ispartof>Biomaterials, 2015-12, Vol.73, p.1-11</ispartof><rights>Elsevier Ltd</rights><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c641t-27f3439434d6c928533f50061a0bf501892e9e3a09db6e4a579cf3a408d04dc43</citedby><cites>FETCH-LOGICAL-c641t-27f3439434d6c928533f50061a0bf501892e9e3a09db6e4a579cf3a408d04dc43</cites><orcidid>0000-0001-7928-5093</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0142961215007383$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26378976$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chan, Angel T</creatorcontrib><creatorcontrib>Karakas, Mehmet F</creatorcontrib><creatorcontrib>Vakrou, Styliani</creatorcontrib><creatorcontrib>Afzal, Junaid</creatorcontrib><creatorcontrib>Rittenbach, Andrew</creatorcontrib><creatorcontrib>Lin, Xiaoping</creatorcontrib><creatorcontrib>Wahl, Richard L</creatorcontrib><creatorcontrib>Pomper, Martin G</creatorcontrib><creatorcontrib>Steenbergen, Charles J</creatorcontrib><creatorcontrib>Tsui, Benjamin M.W</creatorcontrib><creatorcontrib>Elisseeff, Jennifer H</creatorcontrib><creatorcontrib>Abraham, M. Roselle</creatorcontrib><title>Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Abstract Background Cell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and anoikis, which contribute to low engraftment. Objective We tissue engineered scaffolds with the goal of rapidly restoring metabolism, promoting viability, proliferation and engraftment of encapsulated stem cells. Methods The carboxyl groups of HA were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS) groups that react with free amine groups to form amide bonds. HA-NHS was cross-linked by serum to generate HA:Serum (HA:Ser) hydrogels. Physical properties of HA:Ser hydrogels were measured. Effect of encapsulating cardiosphere-derived cells (CDCs) in HA:Ser hydrogels on viability, proliferation, glucose uptake and metabolism was assessed in vitro. In vivo acute intra-myocardial cell retention of18 FDG-labeled CDCs encapsulated in HA:Ser hydrogels was quantified. Effect of CDC encapsulation in HA:Ser hydrogels on in vivo metabolism and engraftment at 7 days was assessed by serial, dual isotope SPECT-CT and bioluminescence imaging of CDCs expressing the Na-iodide symporter and firefly luciferase genes respectively. Effect of HA:Ser hydrogels ± CDCs on cardiac function was assessed at 7 days & 28 days post-infarct. Results HA:Ser hydrogels are highly bio-adhesive, biodegradable, promote rapid cell adhesion, glucose uptake and restore bioenergetics of encapsulated cells within 1 h of encapsulation, both in vitro and in vivo. These metabolic scaffolds can be applied epicardially as a patch to beating hearts or injected intramyocardially. HA:Ser hydrogels markedly increase acute intramyocardial retention (∼6 fold), promote in vivo viability, proliferation, engraftment of encapsulated stem cells and angiogenesis. Conclusion HA:Ser hydrogels serve as ‘synthetic stem cell niches’ that rapidly restore metabolism of encapsulated stem cells, promote stem cell engraftment and angiogenesis. These first ever, tissue engineered metabolic scaffolds hold promise for clinical translation in conjunction with CDCs and possibly other stem cell types.</description><subject>Advanced Basic Science</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biocompatibility</subject><subject>Biocompatible Materials - chemistry</subject><subject>biodegradability</subject><subject>bioluminescence</subject><subject>Biomedical materials</subject><subject>blood serum</subject><subject>cardiac output</subject><subject>Cell Adhesion</subject><subject>Cell Proliferation</subject><subject>Cell Survival</subject><subject>Cell Transplantation</subject><subject>crosslinking</subject><subject>Dentistry</subject><subject>dissociation</subject><subject>Echocardiography</subject><subject>Elastic Modulus</subject><subject>Embryonic Stem Cells - cytology</subject><subject>Encapsulation</subject><subject>energy metabolism</subject><subject>Engraftment</subject><subject>Female</subject><subject>Fluorodeoxyglucose F18 - chemistry</subject><subject>genes</subject><subject>glucose</subject><subject>Glucose - chemistry</subject><subject>HA:Serum hydrogels</subject><subject>heart</subject><subject>Heart - drug effects</subject><subject>Heart - physiology</subject><subject>Humans</subject><subject>Hyaluronic Acid - chemistry</subject><subject>hydrocolloids</subject><subject>Hydrogels</subject><subject>Hydrogels - chemistry</subject><subject>image analysis</subject><subject>in vitro studies</subject><subject>In vivo testing</subject><subject>Intercellular Signaling Peptides and Proteins - metabolism</subject><subject>isotopes</subject><subject>luciferase</subject><subject>Male</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Molecular imaging</subject><subject>Multimodal Imaging</subject><subject>Myocardium - metabolism</subject><subject>necrosis</subject><subject>Neovascularization, Pathologic</subject><subject>niches</subject><subject>physical properties</subject><subject>Rats</subject><subject>Rats, Inbred WKY</subject><subject>Stem Cell Transplantation - instrumentation</subject><subject>Stem Cell Transplantation - methods</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>succinic acid</subject><subject>Surgical implants</subject><subject>symporters</subject><subject>Tissue Engineering</subject><subject>Tissue Scaffolds</subject><subject>Tomography, Emission-Computed, Single-Photon</subject><subject>Tomography, X-Ray Computed</subject><subject>viability</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk9v1DAQxSMEokvhK6CIE5eE8Z_EMYdKqAWKVIkDcLa89mTrJY4XO6mUb4-jLVXhwp5syW_ezPj9iuINgZoAad_t660LXk8YnR5STYE0NcgagDwpNqQTXdVIaJ4WGyCcVrIl9Kx4kdI-Czhw-rw4oy0TnRTtpvDXix7mGEZnSm2crRLG2Ze3i41hh0Mqoz44OyxlxDSFiKXHSW_D4JIvQ1_iaPQhzUMexpZpQl8aHHKVHm15iMGHCbNmF3U_eRynl8WzPo-Mr-7P8-LHp4_fL6-rm6-fv1x-uKlMy8lUUdEzziRn3LZG0q5hrG8AWqJhmy-kkxQlMg3SblvkuhHS9Exz6Cxwazg7Ly6Ovod569Ga3DrqQR2i8zouKmin_n4Z3a3ahTvFZQcgRTZ4e28Qw685r668S-tqesQwJ0UBgDZCAPuvlIiWEkIaTk6QUtHKnMwprpTmqBsis_T9UWpiSCli_7AnAbUCo_bqMTBqBUaBVJmHXPz68U89lP4hJAuujoIMA945jCoZl2NH6yKaSdngTutz8Y-NGVyGTg8_ccG0D3Mc1xqiElWgvq3oruSSnLtgHWO_Afew70Q</recordid><startdate>20151201</startdate><enddate>20151201</enddate><creator>Chan, Angel T</creator><creator>Karakas, Mehmet F</creator><creator>Vakrou, Styliani</creator><creator>Afzal, Junaid</creator><creator>Rittenbach, Andrew</creator><creator>Lin, Xiaoping</creator><creator>Wahl, Richard L</creator><creator>Pomper, Martin G</creator><creator>Steenbergen, Charles J</creator><creator>Tsui, Benjamin M.W</creator><creator>Elisseeff, Jennifer H</creator><creator>Abraham, M. Roselle</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>L7M</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7928-5093</orcidid></search><sort><creationdate>20151201</creationdate><title>Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment</title><author>Chan, Angel T ; Karakas, Mehmet F ; Vakrou, Styliani ; Afzal, Junaid ; Rittenbach, Andrew ; Lin, Xiaoping ; Wahl, Richard L ; Pomper, Martin G ; Steenbergen, Charles J ; Tsui, Benjamin M.W ; Elisseeff, Jennifer H ; Abraham, M. Roselle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641t-27f3439434d6c928533f50061a0bf501892e9e3a09db6e4a579cf3a408d04dc43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Advanced Basic Science</topic><topic>Angiogenesis</topic><topic>Animals</topic><topic>Biocompatibility</topic><topic>Biocompatible Materials - chemistry</topic><topic>biodegradability</topic><topic>bioluminescence</topic><topic>Biomedical materials</topic><topic>blood serum</topic><topic>cardiac output</topic><topic>Cell Adhesion</topic><topic>Cell Proliferation</topic><topic>Cell Survival</topic><topic>Cell Transplantation</topic><topic>crosslinking</topic><topic>Dentistry</topic><topic>dissociation</topic><topic>Echocardiography</topic><topic>Elastic Modulus</topic><topic>Embryonic Stem Cells - cytology</topic><topic>Encapsulation</topic><topic>energy metabolism</topic><topic>Engraftment</topic><topic>Female</topic><topic>Fluorodeoxyglucose F18 - chemistry</topic><topic>genes</topic><topic>glucose</topic><topic>Glucose - chemistry</topic><topic>HA:Serum hydrogels</topic><topic>heart</topic><topic>Heart - drug effects</topic><topic>Heart - physiology</topic><topic>Humans</topic><topic>Hyaluronic Acid - chemistry</topic><topic>hydrocolloids</topic><topic>Hydrogels</topic><topic>Hydrogels - chemistry</topic><topic>image analysis</topic><topic>in vitro studies</topic><topic>In vivo testing</topic><topic>Intercellular Signaling Peptides and Proteins - metabolism</topic><topic>isotopes</topic><topic>luciferase</topic><topic>Male</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Molecular imaging</topic><topic>Multimodal Imaging</topic><topic>Myocardium - metabolism</topic><topic>necrosis</topic><topic>Neovascularization, Pathologic</topic><topic>niches</topic><topic>physical properties</topic><topic>Rats</topic><topic>Rats, Inbred WKY</topic><topic>Stem Cell Transplantation - instrumentation</topic><topic>Stem Cell Transplantation - methods</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>succinic acid</topic><topic>Surgical implants</topic><topic>symporters</topic><topic>Tissue Engineering</topic><topic>Tissue Scaffolds</topic><topic>Tomography, Emission-Computed, Single-Photon</topic><topic>Tomography, X-Ray Computed</topic><topic>viability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chan, Angel T</creatorcontrib><creatorcontrib>Karakas, Mehmet F</creatorcontrib><creatorcontrib>Vakrou, Styliani</creatorcontrib><creatorcontrib>Afzal, Junaid</creatorcontrib><creatorcontrib>Rittenbach, Andrew</creatorcontrib><creatorcontrib>Lin, Xiaoping</creatorcontrib><creatorcontrib>Wahl, Richard L</creatorcontrib><creatorcontrib>Pomper, Martin G</creatorcontrib><creatorcontrib>Steenbergen, Charles J</creatorcontrib><creatorcontrib>Tsui, Benjamin M.W</creatorcontrib><creatorcontrib>Elisseeff, Jennifer H</creatorcontrib><creatorcontrib>Abraham, M. Roselle</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chan, Angel T</au><au>Karakas, Mehmet F</au><au>Vakrou, Styliani</au><au>Afzal, Junaid</au><au>Rittenbach, Andrew</au><au>Lin, Xiaoping</au><au>Wahl, Richard L</au><au>Pomper, Martin G</au><au>Steenbergen, Charles J</au><au>Tsui, Benjamin M.W</au><au>Elisseeff, Jennifer H</au><au>Abraham, M. Roselle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2015-12-01</date><risdate>2015</risdate><volume>73</volume><spage>1</spage><epage>11</epage><pages>1-11</pages><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Abstract Background Cell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and anoikis, which contribute to low engraftment. Objective We tissue engineered scaffolds with the goal of rapidly restoring metabolism, promoting viability, proliferation and engraftment of encapsulated stem cells. Methods The carboxyl groups of HA were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS) groups that react with free amine groups to form amide bonds. HA-NHS was cross-linked by serum to generate HA:Serum (HA:Ser) hydrogels. Physical properties of HA:Ser hydrogels were measured. Effect of encapsulating cardiosphere-derived cells (CDCs) in HA:Ser hydrogels on viability, proliferation, glucose uptake and metabolism was assessed in vitro. In vivo acute intra-myocardial cell retention of18 FDG-labeled CDCs encapsulated in HA:Ser hydrogels was quantified. Effect of CDC encapsulation in HA:Ser hydrogels on in vivo metabolism and engraftment at 7 days was assessed by serial, dual isotope SPECT-CT and bioluminescence imaging of CDCs expressing the Na-iodide symporter and firefly luciferase genes respectively. Effect of HA:Ser hydrogels ± CDCs on cardiac function was assessed at 7 days & 28 days post-infarct. Results HA:Ser hydrogels are highly bio-adhesive, biodegradable, promote rapid cell adhesion, glucose uptake and restore bioenergetics of encapsulated cells within 1 h of encapsulation, both in vitro and in vivo. These metabolic scaffolds can be applied epicardially as a patch to beating hearts or injected intramyocardially. HA:Ser hydrogels markedly increase acute intramyocardial retention (∼6 fold), promote in vivo viability, proliferation, engraftment of encapsulated stem cells and angiogenesis. Conclusion HA:Ser hydrogels serve as ‘synthetic stem cell niches’ that rapidly restore metabolism of encapsulated stem cells, promote stem cell engraftment and angiogenesis. These first ever, tissue engineered metabolic scaffolds hold promise for clinical translation in conjunction with CDCs and possibly other stem cell types.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>26378976</pmid><doi>10.1016/j.biomaterials.2015.09.001</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-7928-5093</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Biomaterials, 2015-12, Vol.73, p.1-11 |
| issn | 0142-9612 1878-5905 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Advanced Basic Science Angiogenesis Animals Biocompatibility Biocompatible Materials - chemistry biodegradability bioluminescence Biomedical materials blood serum cardiac output Cell Adhesion Cell Proliferation Cell Survival Cell Transplantation crosslinking Dentistry dissociation Echocardiography Elastic Modulus Embryonic Stem Cells - cytology Encapsulation energy metabolism Engraftment Female Fluorodeoxyglucose F18 - chemistry genes glucose Glucose - chemistry HA:Serum hydrogels heart Heart - drug effects Heart - physiology Humans Hyaluronic Acid - chemistry hydrocolloids Hydrogels Hydrogels - chemistry image analysis in vitro studies In vivo testing Intercellular Signaling Peptides and Proteins - metabolism isotopes luciferase Male Mesenchymal Stromal Cells - cytology Metabolism Mice Molecular imaging Multimodal Imaging Myocardium - metabolism necrosis Neovascularization, Pathologic niches physical properties Rats Rats, Inbred WKY Stem Cell Transplantation - instrumentation Stem Cell Transplantation - methods Stem cells Stem Cells - cytology succinic acid Surgical implants symporters Tissue Engineering Tissue Scaffolds Tomography, Emission-Computed, Single-Photon Tomography, X-Ray Computed viability |
| title | Hyaluronic acid-serum hydrogels rapidly restore metabolism of encapsulated stem cells and promote engraftment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T21%3A46%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hyaluronic%20acid-serum%20hydrogels%20rapidly%20restore%20metabolism%20of%20encapsulated%20stem%20cells%20and%20promote%20engraftment&rft.jtitle=Biomaterials&rft.au=Chan,%20Angel%20T&rft.date=2015-12-01&rft.volume=73&rft.spage=1&rft.epage=11&rft.pages=1-11&rft.issn=0142-9612&rft.eissn=1878-5905&rft_id=info:doi/10.1016/j.biomaterials.2015.09.001&rft_dat=%3Cproquest_pubme%3E1762111541%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1722187519&rft_id=info:pmid/26378976&rft_els_id=1_s2_0_S0142961215007383&rfr_iscdi=true |