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The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro

Hematopoietic stem and progenitor cell (HSPC) transplantation is a curative treatment of hematological disorders that has been utilized for several decades. Although umbilical cord blood (UCB) is a promising source of HSPCs, the low dose of HSPCs in these preparations limits their use, prompting nee...

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Autores principales: Nii, Takenobu, Konno, Katsuhiro, Matsumoto, Masaki, Bhukhai, Kanit, Borwornpinyo, Suparerk, Sakai, Kazuhiro, Hongeng, Suradej, Sugiyama, Daisuke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036704/
https://www.ncbi.nlm.nih.gov/pubmed/33915948
http://dx.doi.org/10.3390/molecules26071995
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author Nii, Takenobu
Konno, Katsuhiro
Matsumoto, Masaki
Bhukhai, Kanit
Borwornpinyo, Suparerk
Sakai, Kazuhiro
Hongeng, Suradej
Sugiyama, Daisuke
author_facet Nii, Takenobu
Konno, Katsuhiro
Matsumoto, Masaki
Bhukhai, Kanit
Borwornpinyo, Suparerk
Sakai, Kazuhiro
Hongeng, Suradej
Sugiyama, Daisuke
author_sort Nii, Takenobu
collection PubMed
description Hematopoietic stem and progenitor cell (HSPC) transplantation is a curative treatment of hematological disorders that has been utilized for several decades. Although umbilical cord blood (UCB) is a promising source of HSPCs, the low dose of HSPCs in these preparations limits their use, prompting need for ex vivo HSPC expansion. To establish a more efficient method to expand UCB HSPCs, we developed the bioactive peptide named SL-13R and cultured UCB HSPCs (CD34+ cells) with SL-13R in animal component-free medium containing a cytokine cocktail. Following 9 days of culture with SL-13R, the numbers of total cells, CD34+, CD38− cells, and hematopoietic stem cell (HSC)-enriched cells were significantly increased relative to control. Transplantation of cells cultured with SL-13R into immunodeficient NOD/Shi-scid/IL-2Rγ knockout mice confirmed that they possess long-term reconstitution and self-renewal ability. AHNAK, ANXA2, and PLEC all interact with SL-13R. Knockdown of these genes in UCB CD34+ cells resulted in reduced numbers of hematopoietic colonies relative to SL-13R-treated and non-knockdown controls. In summary, we have identified a novel bioactive peptide SL-13R promoting expansion of UCB CD34+ cells with long-term reconstitution and self-renewal ability, suggesting its clinical use in the future.
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spelling pubmed-80367042021-04-12 The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro Nii, Takenobu Konno, Katsuhiro Matsumoto, Masaki Bhukhai, Kanit Borwornpinyo, Suparerk Sakai, Kazuhiro Hongeng, Suradej Sugiyama, Daisuke Molecules Article Hematopoietic stem and progenitor cell (HSPC) transplantation is a curative treatment of hematological disorders that has been utilized for several decades. Although umbilical cord blood (UCB) is a promising source of HSPCs, the low dose of HSPCs in these preparations limits their use, prompting need for ex vivo HSPC expansion. To establish a more efficient method to expand UCB HSPCs, we developed the bioactive peptide named SL-13R and cultured UCB HSPCs (CD34+ cells) with SL-13R in animal component-free medium containing a cytokine cocktail. Following 9 days of culture with SL-13R, the numbers of total cells, CD34+, CD38− cells, and hematopoietic stem cell (HSC)-enriched cells were significantly increased relative to control. Transplantation of cells cultured with SL-13R into immunodeficient NOD/Shi-scid/IL-2Rγ knockout mice confirmed that they possess long-term reconstitution and self-renewal ability. AHNAK, ANXA2, and PLEC all interact with SL-13R. Knockdown of these genes in UCB CD34+ cells resulted in reduced numbers of hematopoietic colonies relative to SL-13R-treated and non-knockdown controls. In summary, we have identified a novel bioactive peptide SL-13R promoting expansion of UCB CD34+ cells with long-term reconstitution and self-renewal ability, suggesting its clinical use in the future. MDPI 2021-04-01 /pmc/articles/PMC8036704/ /pubmed/33915948 http://dx.doi.org/10.3390/molecules26071995 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Nii, Takenobu
Konno, Katsuhiro
Matsumoto, Masaki
Bhukhai, Kanit
Borwornpinyo, Suparerk
Sakai, Kazuhiro
Hongeng, Suradej
Sugiyama, Daisuke
The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro
title The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro
title_full The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro
title_fullStr The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro
title_full_unstemmed The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro
title_short The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro
title_sort bioactive peptide sl-13r expands human umbilical cord blood hematopoietic stem and progenitor cells in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036704/
https://www.ncbi.nlm.nih.gov/pubmed/33915948
http://dx.doi.org/10.3390/molecules26071995
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