Transplantation of Human Placenta Derived Mitochondria Promotes Cell Communication in Endometrium in a Murine Model of Disturbed Endometrium
Objectives Herein, we investigated the regenerative potential of functional mitochondria to restore endometrial injury. Methods The endometrium was disturbed with an intrauterine injection of 95% ethanol. Regeneration of the disturbed endometrium was achieved by transplantation of human placenta der...
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| Veröffentlicht in: | Stem cell reviews and reports 2023-07, Vol.19 (5), p.1384-1401 |
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| creator | Kshersagar, Jeevitaa Pulgam, Lavanya Damle, Mrunal N. Tardalkar, Kishore Sharma, Rakesh Joshi, Meghnad G. |
| description | Objectives
Herein, we investigated the regenerative potential of functional mitochondria to restore endometrial injury.
Methods
The endometrium was disturbed with an intrauterine injection of 95% ethanol. Regeneration of the disturbed endometrium was achieved by transplantation of human placenta derived mitochondria followed by thrombin activated platelet rich plasma (hMTx). The transplantation method provided a biomimetic gel layer that stabilized and supported the functionality of the transplanted mitochondria to flourish regeneration of the disturbed endometrium. The presence of engrafted Rhodamine B labelled mitochondria was quantified at 12, 24, 48, and 72 h after transplantation.
Results
Detection of human-specific mitochondria mRNA in recipient rat uterus showed significant up-regulation of MT ATP-8, MT COX-1, MT COX -3, MT COX -2, MT ATP-6 (p = 0.009) in the hMTx treated group compared to the disturbed endometrium group. The hMTx group demonstrated showed regeneration through increased expressions of α-SMA, CK-18, CK-19, Connexin-40, E Cadherin, Claudin-1, Zona Occludin as compared with disturbed endometrium group. Experimental hMTx endometrial cells had significantly higher values of activities of NADH, NADPH, Cytochrome B5, Cytochrome P450, Complex I, Complex II, Complex III, Complex IV compared with disturbed endometrium indicating the regeneration of damaged endometrial cells at 72 h.
Conclusions
Intrauterine hMTx was accounted to improve endometrial junction protein thus regeneration in the disturbed endometrium. Our Data provide the first evidence that hMTx promotes endometrial regeneration in the disturbed endometrium, paving the way for the development of a novel approach to human endometrial regeneration.
Graphical Abstract |
| doi_str_mv | 10.1007/s12015-023-10516-2 |
| format | Article |
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Herein, we investigated the regenerative potential of functional mitochondria to restore endometrial injury.
Methods
The endometrium was disturbed with an intrauterine injection of 95% ethanol. Regeneration of the disturbed endometrium was achieved by transplantation of human placenta derived mitochondria followed by thrombin activated platelet rich plasma (hMTx). The transplantation method provided a biomimetic gel layer that stabilized and supported the functionality of the transplanted mitochondria to flourish regeneration of the disturbed endometrium. The presence of engrafted Rhodamine B labelled mitochondria was quantified at 12, 24, 48, and 72 h after transplantation.
Results
Detection of human-specific mitochondria mRNA in recipient rat uterus showed significant up-regulation of MT ATP-8, MT COX-1, MT COX -3, MT COX -2, MT ATP-6 (p = 0.009) in the hMTx treated group compared to the disturbed endometrium group. The hMTx group demonstrated showed regeneration through increased expressions of α-SMA, CK-18, CK-19, Connexin-40, E Cadherin, Claudin-1, Zona Occludin as compared with disturbed endometrium group. Experimental hMTx endometrial cells had significantly higher values of activities of NADH, NADPH, Cytochrome B5, Cytochrome P450, Complex I, Complex II, Complex III, Complex IV compared with disturbed endometrium indicating the regeneration of damaged endometrial cells at 72 h.
Conclusions
Intrauterine hMTx was accounted to improve endometrial junction protein thus regeneration in the disturbed endometrium. Our Data provide the first evidence that hMTx promotes endometrial regeneration in the disturbed endometrium, paving the way for the development of a novel approach to human endometrial regeneration.
Graphical Abstract</description><identifier>ISSN: 2629-3269</identifier><identifier>EISSN: 2629-3277</identifier><identifier>DOI: 10.1007/s12015-023-10516-2</identifier><identifier>PMID: 36856954</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animal models ; Biomedical and Life Sciences ; Biomedical Engineering and Bioengineering ; Cell Biology ; Cell interactions ; Cytochrome ; Cytochrome b5 ; Cytochrome P450 ; Endometrium ; Life Sciences ; Mitochondria ; mRNA ; Placenta ; Regenerative Medicine/Tissue Engineering ; Rhodamine ; Stem Cells ; Thrombin ; Transplantation</subject><ispartof>Stem cell reviews and reports, 2023-07, Vol.19 (5), p.1384-1401</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c375t-9d7a35ea3bb89981a37264f8ed6b6660585a7b3b136d0591b4c0a9ce9b806d0a3</citedby><cites>FETCH-LOGICAL-c375t-9d7a35ea3bb89981a37264f8ed6b6660585a7b3b136d0591b4c0a9ce9b806d0a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12015-023-10516-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12015-023-10516-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36856954$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kshersagar, Jeevitaa</creatorcontrib><creatorcontrib>Pulgam, Lavanya</creatorcontrib><creatorcontrib>Damle, Mrunal N.</creatorcontrib><creatorcontrib>Tardalkar, Kishore</creatorcontrib><creatorcontrib>Sharma, Rakesh</creatorcontrib><creatorcontrib>Joshi, Meghnad G.</creatorcontrib><title>Transplantation of Human Placenta Derived Mitochondria Promotes Cell Communication in Endometrium in a Murine Model of Disturbed Endometrium</title><title>Stem cell reviews and reports</title><addtitle>Stem Cell Rev and Rep</addtitle><addtitle>Stem Cell Rev Rep</addtitle><description>Objectives
Herein, we investigated the regenerative potential of functional mitochondria to restore endometrial injury.
Methods
The endometrium was disturbed with an intrauterine injection of 95% ethanol. Regeneration of the disturbed endometrium was achieved by transplantation of human placenta derived mitochondria followed by thrombin activated platelet rich plasma (hMTx). The transplantation method provided a biomimetic gel layer that stabilized and supported the functionality of the transplanted mitochondria to flourish regeneration of the disturbed endometrium. The presence of engrafted Rhodamine B labelled mitochondria was quantified at 12, 24, 48, and 72 h after transplantation.
Results
Detection of human-specific mitochondria mRNA in recipient rat uterus showed significant up-regulation of MT ATP-8, MT COX-1, MT COX -3, MT COX -2, MT ATP-6 (p = 0.009) in the hMTx treated group compared to the disturbed endometrium group. The hMTx group demonstrated showed regeneration through increased expressions of α-SMA, CK-18, CK-19, Connexin-40, E Cadherin, Claudin-1, Zona Occludin as compared with disturbed endometrium group. Experimental hMTx endometrial cells had significantly higher values of activities of NADH, NADPH, Cytochrome B5, Cytochrome P450, Complex I, Complex II, Complex III, Complex IV compared with disturbed endometrium indicating the regeneration of damaged endometrial cells at 72 h.
Conclusions
Intrauterine hMTx was accounted to improve endometrial junction protein thus regeneration in the disturbed endometrium. Our Data provide the first evidence that hMTx promotes endometrial regeneration in the disturbed endometrium, paving the way for the development of a novel approach to human endometrial regeneration.
Graphical Abstract</description><subject>Animal models</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Cell Biology</subject><subject>Cell interactions</subject><subject>Cytochrome</subject><subject>Cytochrome b5</subject><subject>Cytochrome P450</subject><subject>Endometrium</subject><subject>Life Sciences</subject><subject>Mitochondria</subject><subject>mRNA</subject><subject>Placenta</subject><subject>Regenerative Medicine/Tissue Engineering</subject><subject>Rhodamine</subject><subject>Stem Cells</subject><subject>Thrombin</subject><subject>Transplantation</subject><issn>2629-3269</issn><issn>2629-3277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc9OHSEUxompUaO-gIuGpJtuxvJnYIZlc7W1iTd1oWsCM-dazAC3MDTpO_jQch21TRddAYff951z8iF0Rsk5JaT7lCkjVDSE8YYSQWXD9tARk0w1nHXdu7e7VIfoNOcHQipK2qo5QIdc9kIq0R6hx9tkQt5OJsxmdjHguMFXxZuAbyYzQK3iC0juF4x47eY4_IhhTM7gmxR9nCHjFUwTXkXvS3DDYuECvgxj9DAnV_zuafC6JBcAr-MI067HhctzSbba_oWeoP2NmTKcvpzH6O7L5e3qqrn-_vXb6vN1M_BOzI0aO8MFGG5tr1RPDe-YbDc9jNJKKYnohekst5TLkQhFbTsQowZQtie1Yvgx-rj4blP8WSDP2rs81EVMgFiyZl1PGeWqlRX98A_6EEsKdTrN-rZSjLW0UmyhhhRzTrDR2-S8Sb81JXoXl17i0jUD_RyXZlX0_sW6WA_jm-Q1nArwBcj1K9xD-tP7P7ZPlhig5A</recordid><startdate>20230701</startdate><enddate>20230701</enddate><creator>Kshersagar, Jeevitaa</creator><creator>Pulgam, Lavanya</creator><creator>Damle, Mrunal N.</creator><creator>Tardalkar, Kishore</creator><creator>Sharma, Rakesh</creator><creator>Joshi, Meghnad G.</creator><general>Springer US</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</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>FR3</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>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20230701</creationdate><title>Transplantation of Human Placenta Derived Mitochondria Promotes Cell Communication in Endometrium in a Murine Model of Disturbed Endometrium</title><author>Kshersagar, Jeevitaa ; Pulgam, Lavanya ; Damle, Mrunal N. ; Tardalkar, Kishore ; Sharma, Rakesh ; Joshi, Meghnad G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c375t-9d7a35ea3bb89981a37264f8ed6b6660585a7b3b136d0591b4c0a9ce9b806d0a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animal models</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Cell Biology</topic><topic>Cell interactions</topic><topic>Cytochrome</topic><topic>Cytochrome b5</topic><topic>Cytochrome P450</topic><topic>Endometrium</topic><topic>Life Sciences</topic><topic>Mitochondria</topic><topic>mRNA</topic><topic>Placenta</topic><topic>Regenerative Medicine/Tissue Engineering</topic><topic>Rhodamine</topic><topic>Stem Cells</topic><topic>Thrombin</topic><topic>Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kshersagar, Jeevitaa</creatorcontrib><creatorcontrib>Pulgam, Lavanya</creatorcontrib><creatorcontrib>Damle, Mrunal N.</creatorcontrib><creatorcontrib>Tardalkar, Kishore</creatorcontrib><creatorcontrib>Sharma, Rakesh</creatorcontrib><creatorcontrib>Joshi, Meghnad G.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Stem cell reviews and reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kshersagar, Jeevitaa</au><au>Pulgam, Lavanya</au><au>Damle, Mrunal N.</au><au>Tardalkar, Kishore</au><au>Sharma, Rakesh</au><au>Joshi, Meghnad G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transplantation of Human Placenta Derived Mitochondria Promotes Cell Communication in Endometrium in a Murine Model of Disturbed Endometrium</atitle><jtitle>Stem cell reviews and reports</jtitle><stitle>Stem Cell Rev and Rep</stitle><addtitle>Stem Cell Rev Rep</addtitle><date>2023-07-01</date><risdate>2023</risdate><volume>19</volume><issue>5</issue><spage>1384</spage><epage>1401</epage><pages>1384-1401</pages><issn>2629-3269</issn><eissn>2629-3277</eissn><abstract>Objectives
Herein, we investigated the regenerative potential of functional mitochondria to restore endometrial injury.
Methods
The endometrium was disturbed with an intrauterine injection of 95% ethanol. Regeneration of the disturbed endometrium was achieved by transplantation of human placenta derived mitochondria followed by thrombin activated platelet rich plasma (hMTx). The transplantation method provided a biomimetic gel layer that stabilized and supported the functionality of the transplanted mitochondria to flourish regeneration of the disturbed endometrium. The presence of engrafted Rhodamine B labelled mitochondria was quantified at 12, 24, 48, and 72 h after transplantation.
Results
Detection of human-specific mitochondria mRNA in recipient rat uterus showed significant up-regulation of MT ATP-8, MT COX-1, MT COX -3, MT COX -2, MT ATP-6 (p = 0.009) in the hMTx treated group compared to the disturbed endometrium group. The hMTx group demonstrated showed regeneration through increased expressions of α-SMA, CK-18, CK-19, Connexin-40, E Cadherin, Claudin-1, Zona Occludin as compared with disturbed endometrium group. Experimental hMTx endometrial cells had significantly higher values of activities of NADH, NADPH, Cytochrome B5, Cytochrome P450, Complex I, Complex II, Complex III, Complex IV compared with disturbed endometrium indicating the regeneration of damaged endometrial cells at 72 h.
Conclusions
Intrauterine hMTx was accounted to improve endometrial junction protein thus regeneration in the disturbed endometrium. Our Data provide the first evidence that hMTx promotes endometrial regeneration in the disturbed endometrium, paving the way for the development of a novel approach to human endometrial regeneration.
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| subjects | Animal models Biomedical and Life Sciences Biomedical Engineering and Bioengineering Cell Biology Cell interactions Cytochrome Cytochrome b5 Cytochrome P450 Endometrium Life Sciences Mitochondria mRNA Placenta Regenerative Medicine/Tissue Engineering Rhodamine Stem Cells Thrombin Transplantation |
| title | Transplantation of Human Placenta Derived Mitochondria Promotes Cell Communication in Endometrium in a Murine Model of Disturbed Endometrium |
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