Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery
Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneous wound healing; however, it is unknown whether the regenerative properties of this cell type can be applied to diabetic ulcers. ASCs collected from elective surgic...
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| Veröffentlicht in: | Tissue engineering. Part A 2010-05, Vol.16 (5), p.1595-1606 |
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| creator | Amos, Peter J. Kapur, Sahil K. Stapor, Peter C. Shang, Hulan Bekiranov, Stefan Khurgel, Moshe Rodeheaver, George T. Peirce, Shayn M. Katz, Adam J. |
| description | Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneous wound healing; however, it is unknown whether the regenerative properties of this cell type can be applied to diabetic ulcers. ASCs collected from elective surgical procedures were used to treat full-thickness dermal wounds in leptin receptor-deficient (
db/db
) mice. Cells were delivered either as multicellular aggregates or as cell suspensions to determine the impact of cell formulation and delivery methods on biological activity and
in vivo
therapeutic effect. After treatment with ASCs that were formulated as multicellular aggregates, diabetic wounds experienced a significant increase in the rate of wound closure compared to wounds treated with an equal number of ASCs delivered in suspension. Analysis of culture supernatant and gene arrays indicated that ASCs formulated as three-dimensional aggregates produce significantly more extracellular matrix proteins (e.g., tenascin C, collagen VI α3, and fibronectin) and secreted soluble factors (e.g., hepatocyte growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-14) compared to monolayer culture. From these results, it is clear that cell culture, formulation, and delivery method have a large impact on the
in vitro
and
in vivo
biology of ASCs. |
| doi_str_mv | 10.1089/ten.tea.2009.0616 |
| format | Article |
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db/db
) mice. Cells were delivered either as multicellular aggregates or as cell suspensions to determine the impact of cell formulation and delivery methods on biological activity and
in vivo
therapeutic effect. After treatment with ASCs that were formulated as multicellular aggregates, diabetic wounds experienced a significant increase in the rate of wound closure compared to wounds treated with an equal number of ASCs delivered in suspension. Analysis of culture supernatant and gene arrays indicated that ASCs formulated as three-dimensional aggregates produce significantly more extracellular matrix proteins (e.g., tenascin C, collagen VI α3, and fibronectin) and secreted soluble factors (e.g., hepatocyte growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-14) compared to monolayer culture. From these results, it is clear that cell culture, formulation, and delivery method have a large impact on the
in vitro
and
in vivo
biology of ASCs.</description><identifier>ISSN: 1937-3341</identifier><identifier>EISSN: 1937-335X</identifier><identifier>DOI: 10.1089/ten.tea.2009.0616</identifier><identifier>PMID: 20038211</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Adipocytes - cytology ; Adipocytes - metabolism ; Adipocytes - transplantation ; Adipose Tissue - cytology ; Animals ; Cell Aggregation ; Cell Culture Techniques ; Connective tissue cells ; Diabetes Mellitus - pathology ; Drug Delivery Systems - methods ; Enzyme-Linked Immunosorbent Assay ; Extracellular Matrix Proteins - chemistry ; Extracellular Matrix Proteins - metabolism ; Gene Expression Regulation ; Health aspects ; Humans ; Leptin ; Male ; Mass Spectrometry ; Mice ; Original ; Original Articles ; Physiological aspects ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Spheroids, Cellular - cytology ; Stromal Cells - cytology ; Stromal Cells - metabolism ; Stromal Cells - transplantation ; Time Factors ; Wound Healing</subject><ispartof>Tissue engineering. Part A, 2010-05, Vol.16 (5), p.1595-1606</ispartof><rights>2010, Mary Ann Liebert, Inc.</rights><rights>COPYRIGHT 2010 Mary Ann Liebert, Inc.</rights><rights>(©) Copyright 2010, Mary Ann Liebert, Inc.</rights><rights>Copyright 2010, Mary Ann Liebert, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c686t-3bba40ab069fa2952e7c34b92277c7af66a319c79b09adaf0203e4b5da9140853</citedby><cites>FETCH-LOGICAL-c686t-3bba40ab069fa2952e7c34b92277c7af66a319c79b09adaf0203e4b5da9140853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20038211$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Amos, Peter J.</creatorcontrib><creatorcontrib>Kapur, Sahil K.</creatorcontrib><creatorcontrib>Stapor, Peter C.</creatorcontrib><creatorcontrib>Shang, Hulan</creatorcontrib><creatorcontrib>Bekiranov, Stefan</creatorcontrib><creatorcontrib>Khurgel, Moshe</creatorcontrib><creatorcontrib>Rodeheaver, George T.</creatorcontrib><creatorcontrib>Peirce, Shayn M.</creatorcontrib><creatorcontrib>Katz, Adam J.</creatorcontrib><title>Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery</title><title>Tissue engineering. Part A</title><addtitle>Tissue Eng Part A</addtitle><description>Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneous wound healing; however, it is unknown whether the regenerative properties of this cell type can be applied to diabetic ulcers. ASCs collected from elective surgical procedures were used to treat full-thickness dermal wounds in leptin receptor-deficient (
db/db
) mice. Cells were delivered either as multicellular aggregates or as cell suspensions to determine the impact of cell formulation and delivery methods on biological activity and
in vivo
therapeutic effect. After treatment with ASCs that were formulated as multicellular aggregates, diabetic wounds experienced a significant increase in the rate of wound closure compared to wounds treated with an equal number of ASCs delivered in suspension. Analysis of culture supernatant and gene arrays indicated that ASCs formulated as three-dimensional aggregates produce significantly more extracellular matrix proteins (e.g., tenascin C, collagen VI α3, and fibronectin) and secreted soluble factors (e.g., hepatocyte growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-14) compared to monolayer culture. From these results, it is clear that cell culture, formulation, and delivery method have a large impact on the
in vitro
and
in vivo
biology of ASCs.</description><subject>Adipocytes - cytology</subject><subject>Adipocytes - metabolism</subject><subject>Adipocytes - transplantation</subject><subject>Adipose Tissue - cytology</subject><subject>Animals</subject><subject>Cell Aggregation</subject><subject>Cell Culture Techniques</subject><subject>Connective tissue cells</subject><subject>Diabetes Mellitus - pathology</subject><subject>Drug Delivery Systems - methods</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Extracellular Matrix Proteins - chemistry</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Leptin</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Mice</subject><subject>Original</subject><subject>Original Articles</subject><subject>Physiological aspects</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Spheroids, Cellular - cytology</subject><subject>Stromal Cells - cytology</subject><subject>Stromal Cells - metabolism</subject><subject>Stromal Cells - transplantation</subject><subject>Time Factors</subject><subject>Wound Healing</subject><issn>1937-3341</issn><issn>1937-335X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNksFrFDEYxQdRbK3-AV5k0IOnXZNJJpl4EJZd6xYKHlT0Fr7JfLOmZJJtJlPof2_GrYsVDyWEhOT3XsLjFcVLSpaUNOpdQr9MCMuKELUkgopHxSlVTC4Yq388Pu45PSmejeMVIYIIKZ8WJ1nAmorS08JvpwF8uersPoy42GC0N9iVX1IMA7hyjc6N5coYdBghYbmx0GKypvweJt-VWwRn_e59eTHswaQy9L8l5XmIw-Qg2eBLyNwGXfaNt8-LJz24EV_crWfFt_OPX9fbxeXnTxfr1eXCiEakBWtb4ARaIlQPlaorlIbxVlWVlEZCLwQwqoxULVHQQU8qwpC3dQeKctLU7Kz4cPDdT-2AnUGfIji9j3aAeKsDWH3_xtufehdu9PwYpTIbvL0ziOF6wjHpwY45BQcewzRqyWtVNax6AMmYYpxLlcnX_5BXYYo-56BrwoWgNWcZenOAduBQW9-H_D8zW-pVxRtOmJQiU8v_UHl0OFgTPPY2n98T0IPAxDCOEftjFpTouUw6lylP0HOZ9FymrHn1d4hHxZ_2ZEAegPkYvHcWW4zpAda_AOjp2Jg</recordid><startdate>20100501</startdate><enddate>20100501</enddate><creator>Amos, Peter J.</creator><creator>Kapur, Sahil K.</creator><creator>Stapor, Peter C.</creator><creator>Shang, Hulan</creator><creator>Bekiranov, Stefan</creator><creator>Khurgel, Moshe</creator><creator>Rodeheaver, George T.</creator><creator>Peirce, Shayn M.</creator><creator>Katz, Adam J.</creator><general>Mary Ann Liebert, Inc</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>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20100501</creationdate><title>Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery</title><author>Amos, Peter J. ; 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Part A</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Amos, Peter J.</au><au>Kapur, Sahil K.</au><au>Stapor, Peter C.</au><au>Shang, Hulan</au><au>Bekiranov, Stefan</au><au>Khurgel, Moshe</au><au>Rodeheaver, George T.</au><au>Peirce, Shayn M.</au><au>Katz, Adam J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery</atitle><jtitle>Tissue engineering. Part A</jtitle><addtitle>Tissue Eng Part A</addtitle><date>2010-05-01</date><risdate>2010</risdate><volume>16</volume><issue>5</issue><spage>1595</spage><epage>1606</epage><pages>1595-1606</pages><issn>1937-3341</issn><eissn>1937-335X</eissn><abstract>Human adipose-derived stromal cells (ASCs) have been shown to possess therapeutic potential in a variety of settings, including cutaneous wound healing; however, it is unknown whether the regenerative properties of this cell type can be applied to diabetic ulcers. ASCs collected from elective surgical procedures were used to treat full-thickness dermal wounds in leptin receptor-deficient (
db/db
) mice. Cells were delivered either as multicellular aggregates or as cell suspensions to determine the impact of cell formulation and delivery methods on biological activity and
in vivo
therapeutic effect. After treatment with ASCs that were formulated as multicellular aggregates, diabetic wounds experienced a significant increase in the rate of wound closure compared to wounds treated with an equal number of ASCs delivered in suspension. Analysis of culture supernatant and gene arrays indicated that ASCs formulated as three-dimensional aggregates produce significantly more extracellular matrix proteins (e.g., tenascin C, collagen VI α3, and fibronectin) and secreted soluble factors (e.g., hepatocyte growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-14) compared to monolayer culture. From these results, it is clear that cell culture, formulation, and delivery method have a large impact on the
in vitro
and
in vivo
biology of ASCs.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>20038211</pmid><doi>10.1089/ten.tea.2009.0616</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Tissue engineering. Part A, 2010-05, Vol.16 (5), p.1595-1606 |
| issn | 1937-3341 1937-335X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2952117 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adipocytes - cytology Adipocytes - metabolism Adipocytes - transplantation Adipose Tissue - cytology Animals Cell Aggregation Cell Culture Techniques Connective tissue cells Diabetes Mellitus - pathology Drug Delivery Systems - methods Enzyme-Linked Immunosorbent Assay Extracellular Matrix Proteins - chemistry Extracellular Matrix Proteins - metabolism Gene Expression Regulation Health aspects Humans Leptin Male Mass Spectrometry Mice Original Original Articles Physiological aspects RNA, Messenger - genetics RNA, Messenger - metabolism Spheroids, Cellular - cytology Stromal Cells - cytology Stromal Cells - metabolism Stromal Cells - transplantation Time Factors Wound Healing |
| title | Human Adipose-Derived Stromal Cells Accelerate Diabetic Wound Healing: Impact of Cell Formulation and Delivery |
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