Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue

BACKGROUND:Clinical sequelae of irradiation (ischemia, fibrosis, and atrophy) result in tissue devitalization, where wound healing capacity is impaired. Fat or fat-derived products may work to treat such pathology. METHODS:Non-lethal irradiation at various doses (5 Gy, 10 Gy, 15 Gy) and frequencies...

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Veröffentlicht in:Plastic and reconstructive surgery (1963) 2018-08, Vol.142 (2), p.383-391
Hauptverfasser: Wu, Szu-Hsien, Shirado, Takako, Mashiko, Takanobu, Feng, Jingwei, Asahi, Rintaro, Kanayama, Koji, Mori, Masanori, Chi, Daekwan, Sunaga, Ataru, Sarukawa, Shunji, Yoshimura, Kotaro
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container_issue 2
container_start_page 383
container_title Plastic and reconstructive surgery (1963)
container_volume 142
creator Wu, Szu-Hsien
Shirado, Takako
Mashiko, Takanobu
Feng, Jingwei
Asahi, Rintaro
Kanayama, Koji
Mori, Masanori
Chi, Daekwan
Sunaga, Ataru
Sarukawa, Shunji
Yoshimura, Kotaro
description BACKGROUND:Clinical sequelae of irradiation (ischemia, fibrosis, and atrophy) result in tissue devitalization, where wound healing capacity is impaired. Fat or fat-derived products may work to treat such pathology. METHODS:Non-lethal irradiation at various doses (5 Gy, 10 Gy, 15 Gy) and frequencies (1-3 times on sequential days) was delivered to dorsal skin of 7-week-old nude mice, evaluating subsequent gross and microscopic changes for up to 4 weeks. Cutaneous punch wounds were then created, to compare wound healing in irradiated and non-irradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells (ASCs), centrifuged fat tissue, or micronized cellular adipose matrix, monitoring therapeutic impact for up to 15 days. RESULTS:Nude mice given total doses >15 Gy spontaneously developed skin ulcers ~2 weeks after exposure and radiation damage was dose-dependent, but a fractionated irradiation protocol could reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5-15 Gy) impairment of wound healing was also evident. At highest dosage (15 Gy × 3), open wounds persisted on Day 15. However, wounds injected with cultured ASCs were nearly healed on Day 12, and those treated with injection of centrifuged fat or micronized connective tissue healed faster than untreated controls (p
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Fat or fat-derived products may work to treat such pathology. METHODS:Non-lethal irradiation at various doses (5 Gy, 10 Gy, 15 Gy) and frequencies (1-3 times on sequential days) was delivered to dorsal skin of 7-week-old nude mice, evaluating subsequent gross and microscopic changes for up to 4 weeks. Cutaneous punch wounds were then created, to compare wound healing in irradiated and non-irradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells (ASCs), centrifuged fat tissue, or micronized cellular adipose matrix, monitoring therapeutic impact for up to 15 days. RESULTS:Nude mice given total doses &gt;15 Gy spontaneously developed skin ulcers ~2 weeks after exposure and radiation damage was dose-dependent, but a fractionated irradiation protocol could reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5-15 Gy) impairment of wound healing was also evident. At highest dosage (15 Gy × 3), open wounds persisted on Day 15. However, wounds injected with cultured ASCs were nearly healed on Day 12, and those treated with injection of centrifuged fat or micronized connective tissue healed faster than untreated controls (p&lt;0.05). There was no significance between treated groups. CONCLUSIONS:Irradiation damage and tissue devitalization were dose-dependent, though fractionated protocols helped to reduce. ASCs and other fat-derived products harboring ASCs successfully revitalized irradiated tissues and accelerated wound healing.</description><identifier>ISSN: 0032-1052</identifier><identifier>EISSN: 1529-4242</identifier><identifier>DOI: 10.1097/PRS.0000000000004609</identifier><identifier>PMID: 29787514</identifier><language>eng</language><publisher>United States: by the American Society of Plastic Surgeons</publisher><subject>Adipose Tissue - transplantation ; Animals ; Humans ; Male ; Mesenchymal Stem Cell Transplantation ; Mice ; Mice, Nude ; Radiation Injuries, Experimental - therapy ; Skin - pathology ; Skin - radiation effects ; Treatment Outcome ; Wound Healing</subject><ispartof>Plastic and reconstructive surgery (1963), 2018-08, Vol.142 (2), p.383-391</ispartof><rights>by the American Society of Plastic Surgeons</rights><rights>2018American Society of Plastic Surgeons</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5189-baea50f6117b5523ab89f524230df79e4d344e14a8c6304086c24db1c6ee4c183</citedby><cites>FETCH-LOGICAL-c5189-baea50f6117b5523ab89f524230df79e4d344e14a8c6304086c24db1c6ee4c183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29787514$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Szu-Hsien</creatorcontrib><creatorcontrib>Shirado, Takako</creatorcontrib><creatorcontrib>Mashiko, Takanobu</creatorcontrib><creatorcontrib>Feng, Jingwei</creatorcontrib><creatorcontrib>Asahi, Rintaro</creatorcontrib><creatorcontrib>Kanayama, Koji</creatorcontrib><creatorcontrib>Mori, Masanori</creatorcontrib><creatorcontrib>Chi, Daekwan</creatorcontrib><creatorcontrib>Sunaga, Ataru</creatorcontrib><creatorcontrib>Sarukawa, Shunji</creatorcontrib><creatorcontrib>Yoshimura, Kotaro</creatorcontrib><title>Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue</title><title>Plastic and reconstructive surgery (1963)</title><addtitle>Plast Reconstr Surg</addtitle><description>BACKGROUND:Clinical sequelae of irradiation (ischemia, fibrosis, and atrophy) result in tissue devitalization, where wound healing capacity is impaired. Fat or fat-derived products may work to treat such pathology. METHODS:Non-lethal irradiation at various doses (5 Gy, 10 Gy, 15 Gy) and frequencies (1-3 times on sequential days) was delivered to dorsal skin of 7-week-old nude mice, evaluating subsequent gross and microscopic changes for up to 4 weeks. Cutaneous punch wounds were then created, to compare wound healing in irradiated and non-irradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells (ASCs), centrifuged fat tissue, or micronized cellular adipose matrix, monitoring therapeutic impact for up to 15 days. RESULTS:Nude mice given total doses &gt;15 Gy spontaneously developed skin ulcers ~2 weeks after exposure and radiation damage was dose-dependent, but a fractionated irradiation protocol could reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5-15 Gy) impairment of wound healing was also evident. At highest dosage (15 Gy × 3), open wounds persisted on Day 15. However, wounds injected with cultured ASCs were nearly healed on Day 12, and those treated with injection of centrifuged fat or micronized connective tissue healed faster than untreated controls (p&lt;0.05). There was no significance between treated groups. CONCLUSIONS:Irradiation damage and tissue devitalization were dose-dependent, though fractionated protocols helped to reduce. ASCs and other fat-derived products harboring ASCs successfully revitalized irradiated tissues and accelerated wound healing.</description><subject>Adipose Tissue - transplantation</subject><subject>Animals</subject><subject>Humans</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Radiation Injuries, Experimental - therapy</subject><subject>Skin - pathology</subject><subject>Skin - radiation effects</subject><subject>Treatment Outcome</subject><subject>Wound Healing</subject><issn>0032-1052</issn><issn>1529-4242</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUF1LAzEQDKLYWv0HIvcHUpNccpd7LLXaQsGiFR-P3GXPRu-L5M7ivze1KuKDLizL7s4MzCB0TsmYkiS-XN3dj8mP4hFJDtCQCpZgzjg7RENCQoYpEWyATpx7JoTGYSSO0YAlsYwF5UOk1xuwqoW-M3kwKwrIOxc0RTDvK1UHE23axgG-AmteQQcr2-j-A1EHi6pVxvrjY9PXOpiDKk39FBj_sVZpozr_WxvnejhFR4UqHZx9zhF6uJ6tp3O8vL1ZTCdLnAsqE5wpUIIUEaVxJgQLVSaTQngrIdFFnADXIedAuZJ5FBJOZJQzrjOaRwA8pzIcIb7XzW3jnIUiba2plH1LKUl3oaU-tPR3aJ52sae1fVaB_iZ9peQBcg_YNmUH1r2U_RZsuvGWu81_2vwP6g4WiZBjRqgk0m_Yt3fyDtS7iIk</recordid><startdate>20180801</startdate><enddate>20180801</enddate><creator>Wu, Szu-Hsien</creator><creator>Shirado, Takako</creator><creator>Mashiko, Takanobu</creator><creator>Feng, Jingwei</creator><creator>Asahi, Rintaro</creator><creator>Kanayama, Koji</creator><creator>Mori, Masanori</creator><creator>Chi, Daekwan</creator><creator>Sunaga, Ataru</creator><creator>Sarukawa, Shunji</creator><creator>Yoshimura, Kotaro</creator><general>by the American Society of Plastic Surgeons</general><general>American Society of Plastic Surgeons</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></search><sort><creationdate>20180801</creationdate><title>Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue</title><author>Wu, Szu-Hsien ; Shirado, Takako ; Mashiko, Takanobu ; Feng, Jingwei ; Asahi, Rintaro ; Kanayama, Koji ; Mori, Masanori ; Chi, Daekwan ; Sunaga, Ataru ; Sarukawa, Shunji ; Yoshimura, Kotaro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5189-baea50f6117b5523ab89f524230df79e4d344e14a8c6304086c24db1c6ee4c183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adipose Tissue - transplantation</topic><topic>Animals</topic><topic>Humans</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Radiation Injuries, Experimental - therapy</topic><topic>Skin - pathology</topic><topic>Skin - radiation effects</topic><topic>Treatment Outcome</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Szu-Hsien</creatorcontrib><creatorcontrib>Shirado, Takako</creatorcontrib><creatorcontrib>Mashiko, Takanobu</creatorcontrib><creatorcontrib>Feng, Jingwei</creatorcontrib><creatorcontrib>Asahi, Rintaro</creatorcontrib><creatorcontrib>Kanayama, Koji</creatorcontrib><creatorcontrib>Mori, Masanori</creatorcontrib><creatorcontrib>Chi, Daekwan</creatorcontrib><creatorcontrib>Sunaga, Ataru</creatorcontrib><creatorcontrib>Sarukawa, Shunji</creatorcontrib><creatorcontrib>Yoshimura, Kotaro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Plastic and reconstructive surgery (1963)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Szu-Hsien</au><au>Shirado, Takako</au><au>Mashiko, Takanobu</au><au>Feng, Jingwei</au><au>Asahi, Rintaro</au><au>Kanayama, Koji</au><au>Mori, Masanori</au><au>Chi, Daekwan</au><au>Sunaga, Ataru</au><au>Sarukawa, Shunji</au><au>Yoshimura, Kotaro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue</atitle><jtitle>Plastic and reconstructive surgery (1963)</jtitle><addtitle>Plast Reconstr Surg</addtitle><date>2018-08-01</date><risdate>2018</risdate><volume>142</volume><issue>2</issue><spage>383</spage><epage>391</epage><pages>383-391</pages><issn>0032-1052</issn><eissn>1529-4242</eissn><abstract>BACKGROUND:Clinical sequelae of irradiation (ischemia, fibrosis, and atrophy) result in tissue devitalization, where wound healing capacity is impaired. Fat or fat-derived products may work to treat such pathology. METHODS:Non-lethal irradiation at various doses (5 Gy, 10 Gy, 15 Gy) and frequencies (1-3 times on sequential days) was delivered to dorsal skin of 7-week-old nude mice, evaluating subsequent gross and microscopic changes for up to 4 weeks. Cutaneous punch wounds were then created, to compare wound healing in irradiated and non-irradiated states. Wounds were also locally injected with vehicle, cultured adipose-derived stem cells (ASCs), centrifuged fat tissue, or micronized cellular adipose matrix, monitoring therapeutic impact for up to 15 days. RESULTS:Nude mice given total doses &gt;15 Gy spontaneously developed skin ulcers ~2 weeks after exposure and radiation damage was dose-dependent, but a fractionated irradiation protocol could reduce the damage. Histologic assessment revealed dose-dependent dermal fibrosis/thickening and subcutaneous atrophy. Dose-dependent (5-15 Gy) impairment of wound healing was also evident. 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subjects Adipose Tissue - transplantation
Animals
Humans
Male
Mesenchymal Stem Cell Transplantation
Mice
Mice, Nude
Radiation Injuries, Experimental - therapy
Skin - pathology
Skin - radiation effects
Treatment Outcome
Wound Healing
title Therapeutic Effects of Human Adipose-Derived Products on Impaired Wound Healing in Irradiated Tissue
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