Extracellular vesicles from human iPSCs enhance reconstitution capacity of cord blood-derived hematopoietic stem and progenitor cells
Cord blood (CB) represents a source of hematopoietic stem and progenitor cells (CB-HSPCs) for bone marrow (BM) reconstitution, but clinical CB application is limited in adult patients due to the insufficient number of CB-HSCPCs and the lack of effective ex vivo approaches to increase CB-HSPC functio...
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| Veröffentlicht in: | Leukemia 2021-10, Vol.35 (10), p.2964-2977 |
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| creator | Karnas, Elżbieta Sekuła-Stryjewska, Małgorzata Kmiotek-Wasylewska, Katarzyna Bobis-Wozowicz, Sylwia Ryszawy, Damian Sarna, Michał Madeja, Zbigniew Zuba-Surma, Ewa K. |
| description | Cord blood (CB) represents a source of hematopoietic stem and progenitor cells (CB-HSPCs) for bone marrow (BM) reconstitution, but clinical CB application is limited in adult patients due to the insufficient number of CB-HSCPCs and the lack of effective ex vivo approaches to increase CB-HSPC functionality. Since human-induced pluripotent stem cells (hiPSCs) have been indicated as donor cells for bioactive extracellular vesicles (EVs) modulating properties of other cells, we are the first to employ hiPSC-derived EVs (hiPSC-EVs) to enhance the hematopoietic potential of CB-derived CD45
dim
Lin
-
CD34
+
cell fraction enriched in CB-HSPCs. We demonstrated that hiPSC-EVs improved functional properties of CB-HSPCs critical for their hematopoietic capacity including metabolic, hematopoietic and clonogenic potential as well as survival, chemotactic response to stromal cell-derived factor 1 and adhesion to the model components of hematopoietic niche in vitro. Moreover, hiPSC-EVs enhanced homing and engraftment of CB-HSPCs in vivo. This phenomenon might be related to activation of signaling pathways in CB-HSPCs following hiPSC-EV treatment, as shown on both gene expression and the protein kinases activity levels. In conclusion, hiPSC-EVs might be used as ex vivo modulators of CB-HSPCs capacity to enhance their functional properties and augment future practical applications of CB-derived cells in BM reconstitution. |
| doi_str_mv | 10.1038/s41375-021-01325-y |
| format | Article |
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dim
Lin
-
CD34
+
cell fraction enriched in CB-HSPCs. We demonstrated that hiPSC-EVs improved functional properties of CB-HSPCs critical for their hematopoietic capacity including metabolic, hematopoietic and clonogenic potential as well as survival, chemotactic response to stromal cell-derived factor 1 and adhesion to the model components of hematopoietic niche in vitro. Moreover, hiPSC-EVs enhanced homing and engraftment of CB-HSPCs in vivo. This phenomenon might be related to activation of signaling pathways in CB-HSPCs following hiPSC-EV treatment, as shown on both gene expression and the protein kinases activity levels. In conclusion, hiPSC-EVs might be used as ex vivo modulators of CB-HSPCs capacity to enhance their functional properties and augment future practical applications of CB-derived cells in BM reconstitution.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-021-01325-y</identifier><identifier>PMID: 34140648</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/100 ; 13/106 ; 13/2 ; 13/31 ; 14/3 ; 38/39 ; 38/77 ; 631/532/1542 ; 631/61/490 ; 631/80/86 ; 64/60 ; 692/700/565/2319 ; 96/95 ; Animals ; Antigens, CD34 - metabolism ; Blood ; Bone marrow ; Cancer Research ; CD34 antigen ; Chemotactic response ; Cord blood ; Cord Blood Stem Cell Transplantation - methods ; Critical Care Medicine ; Extracellular vesicles ; Extracellular Vesicles - transplantation ; Fetal Blood - cytology ; Gene expression ; Hematology ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - physiology ; Human influences ; Humans ; Induced Pluripotent Stem Cells - cytology ; Induced Pluripotent Stem Cells - physiology ; Intensive ; Internal Medicine ; Kinases ; Male ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Modulators ; Oncology ; Osteoprogenitor cells ; Pluripotency ; Progenitor cells ; Protein kinase ; SDF-1 protein ; Stem cell transplantation ; Stem cells ; Vesicles</subject><ispartof>Leukemia, 2021-10, Vol.35 (10), p.2964-2977</ispartof><rights>The Author(s) 2021</rights><rights>2021. The Author(s).</rights><rights>COPYRIGHT 2021 Nature Publishing Group</rights><rights>The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c572t-733aad91c341eb0b7959685724df8cbf9adc528526622e78280fc5c1a1eab5cf3</citedby><cites>FETCH-LOGICAL-c572t-733aad91c341eb0b7959685724df8cbf9adc528526622e78280fc5c1a1eab5cf3</cites><orcidid>0000-0001-9956-1593 ; 0000-0002-2200-6767 ; 0000-0001-6814-6127</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/s41375-021-01325-y$$EPDF$$P50$$Gspringer$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/s41375-021-01325-y$$EHTML$$P50$$Gspringer$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34140648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Karnas, Elżbieta</creatorcontrib><creatorcontrib>Sekuła-Stryjewska, Małgorzata</creatorcontrib><creatorcontrib>Kmiotek-Wasylewska, Katarzyna</creatorcontrib><creatorcontrib>Bobis-Wozowicz, Sylwia</creatorcontrib><creatorcontrib>Ryszawy, Damian</creatorcontrib><creatorcontrib>Sarna, Michał</creatorcontrib><creatorcontrib>Madeja, Zbigniew</creatorcontrib><creatorcontrib>Zuba-Surma, Ewa K.</creatorcontrib><title>Extracellular vesicles from human iPSCs enhance reconstitution capacity of cord blood-derived hematopoietic stem and progenitor cells</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>Cord blood (CB) represents a source of hematopoietic stem and progenitor cells (CB-HSPCs) for bone marrow (BM) reconstitution, but clinical CB application is limited in adult patients due to the insufficient number of CB-HSCPCs and the lack of effective ex vivo approaches to increase CB-HSPC functionality. Since human-induced pluripotent stem cells (hiPSCs) have been indicated as donor cells for bioactive extracellular vesicles (EVs) modulating properties of other cells, we are the first to employ hiPSC-derived EVs (hiPSC-EVs) to enhance the hematopoietic potential of CB-derived CD45
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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Karnas, Elżbieta</au><au>Sekuła-Stryjewska, Małgorzata</au><au>Kmiotek-Wasylewska, Katarzyna</au><au>Bobis-Wozowicz, Sylwia</au><au>Ryszawy, Damian</au><au>Sarna, Michał</au><au>Madeja, Zbigniew</au><au>Zuba-Surma, Ewa K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Extracellular vesicles from human iPSCs enhance reconstitution capacity of cord blood-derived hematopoietic stem and progenitor cells</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2021-10-01</date><risdate>2021</risdate><volume>35</volume><issue>10</issue><spage>2964</spage><epage>2977</epage><pages>2964-2977</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><abstract>Cord blood (CB) represents a source of hematopoietic stem and progenitor cells (CB-HSPCs) for bone marrow (BM) reconstitution, but clinical CB application is limited in adult patients due to the insufficient number of CB-HSCPCs and the lack of effective ex vivo approaches to increase CB-HSPC functionality. Since human-induced pluripotent stem cells (hiPSCs) have been indicated as donor cells for bioactive extracellular vesicles (EVs) modulating properties of other cells, we are the first to employ hiPSC-derived EVs (hiPSC-EVs) to enhance the hematopoietic potential of CB-derived CD45
dim
Lin
-
CD34
+
cell fraction enriched in CB-HSPCs. We demonstrated that hiPSC-EVs improved functional properties of CB-HSPCs critical for their hematopoietic capacity including metabolic, hematopoietic and clonogenic potential as well as survival, chemotactic response to stromal cell-derived factor 1 and adhesion to the model components of hematopoietic niche in vitro. Moreover, hiPSC-EVs enhanced homing and engraftment of CB-HSPCs in vivo. This phenomenon might be related to activation of signaling pathways in CB-HSPCs following hiPSC-EV treatment, as shown on both gene expression and the protein kinases activity levels. In conclusion, hiPSC-EVs might be used as ex vivo modulators of CB-HSPCs capacity to enhance their functional properties and augment future practical applications of CB-derived cells in BM reconstitution.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>34140648</pmid><doi>10.1038/s41375-021-01325-y</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-9956-1593</orcidid><orcidid>https://orcid.org/0000-0002-2200-6767</orcidid><orcidid>https://orcid.org/0000-0001-6814-6127</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2021-10, Vol.35 (10), p.2964-2977 |
| issn | 0887-6924 1476-5551 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8478657 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | 13/100 13/106 13/2 13/31 14/3 38/39 38/77 631/532/1542 631/61/490 631/80/86 64/60 692/700/565/2319 96/95 Animals Antigens, CD34 - metabolism Blood Bone marrow Cancer Research CD34 antigen Chemotactic response Cord blood Cord Blood Stem Cell Transplantation - methods Critical Care Medicine Extracellular vesicles Extracellular Vesicles - transplantation Fetal Blood - cytology Gene expression Hematology Hematopoiesis Hematopoietic Stem Cell Transplantation - methods Hematopoietic stem cells Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - physiology Human influences Humans Induced Pluripotent Stem Cells - cytology Induced Pluripotent Stem Cells - physiology Intensive Internal Medicine Kinases Male Medicine Medicine & Public Health Mice Mice, Inbred NOD Mice, SCID Modulators Oncology Osteoprogenitor cells Pluripotency Progenitor cells Protein kinase SDF-1 protein Stem cell transplantation Stem cells Vesicles |
| title | Extracellular vesicles from human iPSCs enhance reconstitution capacity of cord blood-derived hematopoietic stem and progenitor cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T20%3A56%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Extracellular%20vesicles%20from%20human%20iPSCs%20enhance%20reconstitution%20capacity%20of%20cord%20blood-derived%20hematopoietic%20stem%20and%20progenitor%20cells&rft.jtitle=Leukemia&rft.au=Karnas,%20El%C5%BCbieta&rft.date=2021-10-01&rft.volume=35&rft.issue=10&rft.spage=2964&rft.epage=2977&rft.pages=2964-2977&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/s41375-021-01325-y&rft_dat=%3Cgale_pubme%3EA677107883%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2577215041&rft_id=info:pmid/34140648&rft_galeid=A677107883&rfr_iscdi=true |