Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment

BACKGROUND Platelet engraftment following cord blood (CB) transplantation remains a significant hurdle to this day. The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. W...

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Veröffentlicht in:	Transfusion (Philadelphia, Pa.) Pa.), 2020-04, Vol.60 (4), p.769-778
Hauptverfasser:	Jahan, Suria, Adam, Madeleine K., Manesia, Javed K., Doxtator, Emily, Ben, Robert N., Pineault, Nicolas
Format:	Artikel
Sprache:	eng
Schlagworte:	Blood Blood platelets Bone marrow Cell self-renewal Chimerism Cord blood Cryopreservation Dimethyl sulfoxide Engraftment Erythrocytes Freeze-thaw durability Freezing Hematopoietic stem cells Ice Immunodeficiency Osteoprogenitor cells Peripheral blood Platelets Progenitor cells Recrystallization Stem cell transplantation Stem cells Thawing Transplantation Transplants & implants
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creator	Jahan, Suria Adam, Madeleine K. Manesia, Javed K. Doxtator, Emily Ben, Robert N. Pineault, Nicolas
description	BACKGROUND Platelet engraftment following cord blood (CB) transplantation remains a significant hurdle to this day. The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. We hypothesized that reducing cell damage induced by ice recrystallization in CB units (CBUs) would reduce losses of stem and progenitor cells and therefore improve engraftment. We previously demonstrated that the ice recrystallization inhibitor (IRI) N‐(2‐fluorophenyl)‐D‐gluconamide (IRI 2) increases the postthaw recovery of CB progenitors. Herein, we set out to ascertain whether IRI 2 can enhance platelet and bone marrow engraftment activity of hematopoietic stem cells (HSCs) in cryopreserved CBUs using a serial transplantation model. STUDY DESIGN AND METHODS CBUs were processed following standard volume/red blood cell reduction procedure and portions frozen with dimethyl sulfoxide (DMSO) supplemented or not with IRI 2. Thawed CB samples were serially transplanted into immunodeficient mice. RESULTS Our results show that supplementation of DMSO with IRI 2 had several beneficial effects. Specifically, higher levels of human platelets were observed in the peripheral blood (p
doi_str_mv	10.1111/trf.15759
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The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. We hypothesized that reducing cell damage induced by ice recrystallization in CB units (CBUs) would reduce losses of stem and progenitor cells and therefore improve engraftment. We previously demonstrated that the ice recrystallization inhibitor (IRI) N‐(2‐fluorophenyl)‐D‐gluconamide (IRI 2) increases the postthaw recovery of CB progenitors. Herein, we set out to ascertain whether IRI 2 can enhance platelet and bone marrow engraftment activity of hematopoietic stem cells (HSCs) in cryopreserved CBUs using a serial transplantation model. STUDY DESIGN AND METHODS CBUs were processed following standard volume/red blood cell reduction procedure and portions frozen with dimethyl sulfoxide (DMSO) supplemented or not with IRI 2. Thawed CB samples were serially transplanted into immunodeficient mice. RESULTS Our results show that supplementation of DMSO with IRI 2 had several beneficial effects. Specifically, higher levels of human platelets were observed in the peripheral blood (p < 0.05; n = 4) upon transplant of CBUs preserved with the IRIs. In addition, human BM chimerism and the number of human CFU progenitors in the bone marrow were superior in IRI 2 recipients compared to DMSO recipients. Moreover, IRI 2 had no negative impact on the multilineage differentiation and self‐renewal activities of HSCs. DISCUSSION Taken together, these results demonstrate that supplementation of a hematopoietic graft with IRI can improve the postthaw engraftment activities of HSCs.</description><identifier>ISSN: 0041-1132</identifier><identifier>EISSN: 1537-2995</identifier><identifier>DOI: 10.1111/trf.15759</identifier><identifier>PMID: 32187691</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Blood ; Blood platelets ; Bone marrow ; Cell self-renewal ; Chimerism ; Cord blood ; Cryopreservation ; Dimethyl sulfoxide ; Engraftment ; Erythrocytes ; Freeze-thaw durability ; Freezing ; Hematopoietic stem cells ; Ice ; Immunodeficiency ; Osteoprogenitor cells ; Peripheral blood ; Platelets ; Progenitor cells ; Recrystallization ; Stem cell transplantation ; Stem cells ; Thawing ; Transplantation ; Transplants & implants</subject><ispartof>Transfusion (Philadelphia, Pa.), 2020-04, Vol.60 (4), p.769-778</ispartof><rights>2020 AABB</rights><rights>2020 AABB.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3539-cdb872c8460d96b9469d1d719e424dee8fc046a922d13f6147243837cf806b433</citedby><cites>FETCH-LOGICAL-c3539-cdb872c8460d96b9469d1d719e424dee8fc046a922d13f6147243837cf806b433</cites><orcidid>0000-0002-0082-0944</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Ftrf.15759$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Ftrf.15759$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32187691$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jahan, Suria</creatorcontrib><creatorcontrib>Adam, Madeleine K.</creatorcontrib><creatorcontrib>Manesia, Javed K.</creatorcontrib><creatorcontrib>Doxtator, Emily</creatorcontrib><creatorcontrib>Ben, Robert N.</creatorcontrib><creatorcontrib>Pineault, Nicolas</creatorcontrib><title>Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment</title><title>Transfusion (Philadelphia, Pa.)</title><addtitle>Transfusion</addtitle><description>BACKGROUND Platelet engraftment following cord blood (CB) transplantation remains a significant hurdle to this day. The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. We hypothesized that reducing cell damage induced by ice recrystallization in CB units (CBUs) would reduce losses of stem and progenitor cells and therefore improve engraftment. We previously demonstrated that the ice recrystallization inhibitor (IRI) N‐(2‐fluorophenyl)‐D‐gluconamide (IRI 2) increases the postthaw recovery of CB progenitors. Herein, we set out to ascertain whether IRI 2 can enhance platelet and bone marrow engraftment activity of hematopoietic stem cells (HSCs) in cryopreserved CBUs using a serial transplantation model. STUDY DESIGN AND METHODS CBUs were processed following standard volume/red blood cell reduction procedure and portions frozen with dimethyl sulfoxide (DMSO) supplemented or not with IRI 2. Thawed CB samples were serially transplanted into immunodeficient mice. RESULTS Our results show that supplementation of DMSO with IRI 2 had several beneficial effects. Specifically, higher levels of human platelets were observed in the peripheral blood (p < 0.05; n = 4) upon transplant of CBUs preserved with the IRIs. In addition, human BM chimerism and the number of human CFU progenitors in the bone marrow were superior in IRI 2 recipients compared to DMSO recipients. Moreover, IRI 2 had no negative impact on the multilineage differentiation and self‐renewal activities of HSCs. DISCUSSION Taken together, these results demonstrate that supplementation of a hematopoietic graft with IRI can improve the postthaw engraftment activities of HSCs.</description><subject>Blood</subject><subject>Blood platelets</subject><subject>Bone marrow</subject><subject>Cell self-renewal</subject><subject>Chimerism</subject><subject>Cord blood</subject><subject>Cryopreservation</subject><subject>Dimethyl sulfoxide</subject><subject>Engraftment</subject><subject>Erythrocytes</subject><subject>Freeze-thaw durability</subject><subject>Freezing</subject><subject>Hematopoietic stem cells</subject><subject>Ice</subject><subject>Immunodeficiency</subject><subject>Osteoprogenitor cells</subject><subject>Peripheral blood</subject><subject>Platelets</subject><subject>Progenitor cells</subject><subject>Recrystallization</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Thawing</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>0041-1132</issn><issn>1537-2995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp10c9LHDEUB_AgLe529dB_oAR60cNoXpL5kWORaoUFoeh5yCRvNEtmsk1mLNu_3rirPRSaSyDvky-P9wj5DOwC8rmcYn8BZV2qI7KEUtQFV6r8QJaMSSgABF-QTyltGGNcMTgmC8GhqSsFSzLejk-uc5MLIw09dQZpRBN3adLeuz96X7BzdOMjzc9hGzFhfNbvH0yIlnY-BEsfo-6nRN2wjeEZE916PaHHieK4Lw04TifkY699wtO3e0Uerr_fX_0o1nc3t1ff1oURpVCFsV1Tc9PIillVdUpWyoKtQaHk0iI2vWGy0opzC6KvQNZcikbUpm9Y1UkhVuTskJt7-TVjmtrBJYPe6xHDnFou6jwJUUnI9Os_dBPmOObusmrKzDjwrM4PysSQUsS-3UY36LhrgbWvS2jzEtr9ErL98pY4dwPav_J96hlcHsBv53H3_6T2_uf1IfIFs9qSBA</recordid><startdate>202004</startdate><enddate>202004</enddate><creator>Jahan, Suria</creator><creator>Adam, Madeleine K.</creator><creator>Manesia, Javed K.</creator><creator>Doxtator, Emily</creator><creator>Ben, Robert N.</creator><creator>Pineault, Nicolas</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0082-0944</orcidid></search><sort><creationdate>202004</creationdate><title>Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment</title><author>Jahan, Suria ; Adam, Madeleine K. ; Manesia, Javed K. ; Doxtator, Emily ; Ben, Robert N. ; Pineault, Nicolas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3539-cdb872c8460d96b9469d1d719e424dee8fc046a922d13f6147243837cf806b433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Blood</topic><topic>Blood platelets</topic><topic>Bone marrow</topic><topic>Cell self-renewal</topic><topic>Chimerism</topic><topic>Cord blood</topic><topic>Cryopreservation</topic><topic>Dimethyl sulfoxide</topic><topic>Engraftment</topic><topic>Erythrocytes</topic><topic>Freeze-thaw durability</topic><topic>Freezing</topic><topic>Hematopoietic stem cells</topic><topic>Ice</topic><topic>Immunodeficiency</topic><topic>Osteoprogenitor cells</topic><topic>Peripheral blood</topic><topic>Platelets</topic><topic>Progenitor cells</topic><topic>Recrystallization</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Thawing</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jahan, Suria</creatorcontrib><creatorcontrib>Adam, Madeleine K.</creatorcontrib><creatorcontrib>Manesia, Javed K.</creatorcontrib><creatorcontrib>Doxtator, Emily</creatorcontrib><creatorcontrib>Ben, Robert N.</creatorcontrib><creatorcontrib>Pineault, Nicolas</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transfusion (Philadelphia, Pa.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jahan, Suria</au><au>Adam, Madeleine K.</au><au>Manesia, Javed K.</au><au>Doxtator, Emily</au><au>Ben, Robert N.</au><au>Pineault, Nicolas</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment</atitle><jtitle>Transfusion (Philadelphia, Pa.)</jtitle><addtitle>Transfusion</addtitle><date>2020-04</date><risdate>2020</risdate><volume>60</volume><issue>4</issue><spage>769</spage><epage>778</epage><pages>769-778</pages><issn>0041-1132</issn><eissn>1537-2995</eissn><abstract>BACKGROUND Platelet engraftment following cord blood (CB) transplantation remains a significant hurdle to this day. The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. We hypothesized that reducing cell damage induced by ice recrystallization in CB units (CBUs) would reduce losses of stem and progenitor cells and therefore improve engraftment. We previously demonstrated that the ice recrystallization inhibitor (IRI) N‐(2‐fluorophenyl)‐D‐gluconamide (IRI 2) increases the postthaw recovery of CB progenitors. Herein, we set out to ascertain whether IRI 2 can enhance platelet and bone marrow engraftment activity of hematopoietic stem cells (HSCs) in cryopreserved CBUs using a serial transplantation model. STUDY DESIGN AND METHODS CBUs were processed following standard volume/red blood cell reduction procedure and portions frozen with dimethyl sulfoxide (DMSO) supplemented or not with IRI 2. Thawed CB samples were serially transplanted into immunodeficient mice. RESULTS Our results show that supplementation of DMSO with IRI 2 had several beneficial effects. Specifically, higher levels of human platelets were observed in the peripheral blood (p < 0.05; n = 4) upon transplant of CBUs preserved with the IRIs. In addition, human BM chimerism and the number of human CFU progenitors in the bone marrow were superior in IRI 2 recipients compared to DMSO recipients. Moreover, IRI 2 had no negative impact on the multilineage differentiation and self‐renewal activities of HSCs. DISCUSSION Taken together, these results demonstrate that supplementation of a hematopoietic graft with IRI can improve the postthaw engraftment activities of HSCs.</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>32187691</pmid><doi>10.1111/trf.15759</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-0082-0944</orcidid></addata></record>
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subjects	Blood Blood platelets Bone marrow Cell self-renewal Chimerism Cord blood Cryopreservation Dimethyl sulfoxide Engraftment Erythrocytes Freeze-thaw durability Freezing Hematopoietic stem cells Ice Immunodeficiency Osteoprogenitor cells Peripheral blood Platelets Progenitor cells Recrystallization Stem cell transplantation Stem cells Thawing Transplantation Transplants & implants
title	Inhibition of ice recrystallization during cryopreservation of cord blood grafts improves platelet engraftment
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