Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783676972537217024 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8036704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT niitakenobu thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT konnokatsuhiro thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT matsumotomasaki thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT bhukhaikanit thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT borwornpinyosuparerk thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT sakaikazuhiro thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT hongengsuradej thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT sugiyamadaisuke thebioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT niitakenobu bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT konnokatsuhiro bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT matsumotomasaki bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT bhukhaikanit bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT borwornpinyosuparerk bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT sakaikazuhiro bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT hongengsuradej bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro AT sugiyamadaisuke bioactivepeptidesl13rexpandshumanumbilicalcordbloodhematopoieticstemandprogenitorcellsinvitro |