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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Main Authors: Takenobu Nii, Katsuhiro Konno, Masaki Matsumoto, Kanit Bhukhai, Suparerk Borwornpinyo, Kazuhiro Sakai, Suradej Hongeng, Daisuke Sugiyama
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/26/7/1995
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author Takenobu Nii
Katsuhiro Konno
Masaki Matsumoto
Kanit Bhukhai
Suparerk Borwornpinyo
Kazuhiro Sakai
Suradej Hongeng
Daisuke Sugiyama
author_facet Takenobu Nii
Katsuhiro Konno
Masaki Matsumoto
Kanit Bhukhai
Suparerk Borwornpinyo
Kazuhiro Sakai
Suradej Hongeng
Daisuke Sugiyama
author_sort Takenobu Nii
collection DOAJ
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 doaj.art-37f7a2ccf8844156b47423597bf7979e2023-11-21T13:46:25ZengMDPI AGMolecules1420-30492021-04-01267199510.3390/molecules26071995The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In VitroTakenobu Nii0Katsuhiro Konno1Masaki Matsumoto2Kanit Bhukhai3Suparerk Borwornpinyo4Kazuhiro Sakai5Suradej Hongeng6Daisuke Sugiyama7Incubation Center for Advanced Medical Science, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, JapanIncubation Center for Advanced Medical Science, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, JapanDivision of Cell Biology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, JapanDepartment of Physiology, Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchatewi, Bangkok 10400, ThailandDepartment of Biotechnology, Faculty of Science, Mahidol University, 272 Rama VI Road, Ratchatewi, Bangkok 10400, ThailandAngel Hospital, 1-11-1 Tomoda, Yahatanishiku, Kitakyushu 807-0828, JapanDepartment of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, 270 Rama VI Road, Ratchatewi, Bangkok 10400, ThailandIncubation Center for Advanced Medical Science, Kyushu University, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582, JapanHematopoietic 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.https://www.mdpi.com/1420-3049/26/7/1995umbilical cord bloodhematopoietic stem/progenitor cellpeptidecell culture
spellingShingle Takenobu Nii
Katsuhiro Konno
Masaki Matsumoto
Kanit Bhukhai
Suparerk Borwornpinyo
Kazuhiro Sakai
Suradej Hongeng
Daisuke Sugiyama
The Bioactive Peptide SL-13R Expands Human Umbilical Cord Blood Hematopoietic Stem and Progenitor Cells In Vitro
Molecules
umbilical cord blood
hematopoietic stem/progenitor cell
peptide
cell culture
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 umbilical cord blood
hematopoietic stem/progenitor cell
peptide
cell culture
url https://www.mdpi.com/1420-3049/26/7/1995
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