Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions
Amidst the global shortfalls in blood supply, storage limitations of donor blood and the availability of potential blood substitutes for transfusion applications, society has pivoted towards in vitro generation of red blood cells (RBCs) as a means to solve these issues. Many conventional research st...
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Veröffentlicht in: | International journal of molecular sciences 2021-09, Vol.22 (18), p.9808 |
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container_title | International journal of molecular sciences |
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creator | Lim, Zhong Ri Vassilev, Svetlan Leong, Yew Wai Hang, Jing Wen Rénia, Laurent Malleret, Benoit Oh, Steve Kah-Weng |
description | Amidst the global shortfalls in blood supply, storage limitations of donor blood and the availability of potential blood substitutes for transfusion applications, society has pivoted towards in vitro generation of red blood cells (RBCs) as a means to solve these issues. Many conventional research studies over the past few decades have found success in differentiating hematopoietic stem and progenitor cells (HSPCs) from cord blood, adult bone marrow and peripheral blood sources. More recently, techniques that involve immortalization of erythroblast sources have also gained traction in tackling this problem. However, the RBCs generated from human induced pluripotent stem cells (hiPSCs) still remain as the most favorable solution due to many of its added advantages. In this review, we focus on the breakthroughs for high-density cultures of hiPSC-derived RBCs, and highlight the major challenges and prospective solutions throughout the whole process of erythropoiesis for hiPSC-derived RBCs. Furthermore, we elaborate on the recent advances and techniques used to achieve cost-effective, high-density cultures of GMP-compliant RBCs, and on their relevant novel applications after downstream processing and purification. |
doi_str_mv | 10.3390/ijms22189808 |
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Many conventional research studies over the past few decades have found success in differentiating hematopoietic stem and progenitor cells (HSPCs) from cord blood, adult bone marrow and peripheral blood sources. More recently, techniques that involve immortalization of erythroblast sources have also gained traction in tackling this problem. However, the RBCs generated from human induced pluripotent stem cells (hiPSCs) still remain as the most favorable solution due to many of its added advantages. In this review, we focus on the breakthroughs for high-density cultures of hiPSC-derived RBCs, and highlight the major challenges and prospective solutions throughout the whole process of erythropoiesis for hiPSC-derived RBCs. Furthermore, we elaborate on the recent advances and techniques used to achieve cost-effective, high-density cultures of GMP-compliant RBCs, and on their relevant novel applications after downstream processing and purification.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22189808</identifier><identifier>PMID: 34575977</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Blood & organ donations ; Blood banks ; Blood substitutes ; Blood transfusion ; Blood transfusions ; Bone marrow ; Cell differentiation ; Clinical trials ; Cord blood ; Coronaviruses ; COVID-19 ; Erythrocytes ; Erythropoiesis ; FDA approval ; Hematopoietic stem cells ; Hemoglobin ; Immortalization ; Pandemics ; Perfluorocarbons ; Peripheral blood ; Pluripotency ; Progenitor cells ; Review ; Shortages ; Stem cells</subject><ispartof>International journal of molecular sciences, 2021-09, Vol.22 (18), p.9808</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-5fc8aac9dd5f6189fce78546a90d5dedc56da4362a14e05d49dc4032b68b39d93</citedby><cites>FETCH-LOGICAL-c389t-5fc8aac9dd5f6189fce78546a90d5dedc56da4362a14e05d49dc4032b68b39d93</cites><orcidid>0000-0001-9658-7528</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472628/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472628/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids></links><search><creatorcontrib>Lim, Zhong Ri</creatorcontrib><creatorcontrib>Vassilev, Svetlan</creatorcontrib><creatorcontrib>Leong, Yew Wai</creatorcontrib><creatorcontrib>Hang, Jing Wen</creatorcontrib><creatorcontrib>Rénia, Laurent</creatorcontrib><creatorcontrib>Malleret, Benoit</creatorcontrib><creatorcontrib>Oh, Steve Kah-Weng</creatorcontrib><title>Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions</title><title>International journal of molecular sciences</title><description>Amidst the global shortfalls in blood supply, storage limitations of donor blood and the availability of potential blood substitutes for transfusion applications, society has pivoted towards in vitro generation of red blood cells (RBCs) as a means to solve these issues. 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Furthermore, we elaborate on the recent advances and techniques used to achieve cost-effective, high-density cultures of GMP-compliant RBCs, and on their relevant novel applications after downstream processing and purification.</description><subject>Blood & organ donations</subject><subject>Blood banks</subject><subject>Blood substitutes</subject><subject>Blood transfusion</subject><subject>Blood transfusions</subject><subject>Bone marrow</subject><subject>Cell differentiation</subject><subject>Clinical trials</subject><subject>Cord blood</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>Erythrocytes</subject><subject>Erythropoiesis</subject><subject>FDA approval</subject><subject>Hematopoietic stem cells</subject><subject>Hemoglobin</subject><subject>Immortalization</subject><subject>Pandemics</subject><subject>Perfluorocarbons</subject><subject>Peripheral blood</subject><subject>Pluripotency</subject><subject>Progenitor cells</subject><subject>Review</subject><subject>Shortages</subject><subject>Stem cells</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkctO3TAQhi1EBRS66wNE6oYFKY7v7qJSG1pAQioCurZ8bOfgo8Q-eBIk3p5EoIqymhn93_yaC0KfG_yVUo1P42YAQhqlFVY76KBhhNQYC7n7Jt9HHwE2GBNKuN5D-5RxybWUB6i7TH6CsUTb909Vm4etHeOqD9VdsQm6CexSxOvbtj4LJT4GX938bOFbdV3yugSAk6q9n3tDWgeobPKLANvgxpmtbnM_jTEnOEIfOttD-PQaD9Hf37_u2ov66s_5ZfvjqnZU6bHmnVPWOu0978S8UueCVJwJq7HnPnjHhbeMCmIbFjD3THvHMCUroVZUe00P0fcX3-20GmY-pLHY3mxLHGx5MtlG87-S4r1Z50ejmCSCqNng-NWg5IcpwGiGCC70vU0hT2AIl5IJKjmf0S_v0E2eSprXWyjBaNOQhTp5odx8Fyih-zdMg83yQPP2gfQZrziO_w</recordid><startdate>20210910</startdate><enddate>20210910</enddate><creator>Lim, Zhong Ri</creator><creator>Vassilev, Svetlan</creator><creator>Leong, Yew Wai</creator><creator>Hang, Jing Wen</creator><creator>Rénia, Laurent</creator><creator>Malleret, Benoit</creator><creator>Oh, Steve Kah-Weng</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9658-7528</orcidid></search><sort><creationdate>20210910</creationdate><title>Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions</title><author>Lim, Zhong Ri ; 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subjects | Blood & organ donations Blood banks Blood substitutes Blood transfusion Blood transfusions Bone marrow Cell differentiation Clinical trials Cord blood Coronaviruses COVID-19 Erythrocytes Erythropoiesis FDA approval Hematopoietic stem cells Hemoglobin Immortalization Pandemics Perfluorocarbons Peripheral blood Pluripotency Progenitor cells Review Shortages Stem cells |
title | Industrially Compatible Transfusable iPSC-Derived RBCs: Progress, Challenges and Prospective Solutions |
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