Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa
Hematopoietic stem cells (HSCs, CD34+ cells) have shown therapeutic efficacy for transplantation in various hematological disorders. However, a large quantity of HSCs is required for transplantation. Therefore, strategies to increase HSC numbers and preserve HSC functions through ex vivo culture are...
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2021-11-01
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doaj-0a3de88084044f56bc26566c79a88a3d2021-10-11T04:14:33ZengElsevierBiomedicine & Pharmacotherapy0753-33222021-11-01143112102Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosaNopmullee Tanhuad0Umnuaychoke Thongsa-ad1Nareerat Sutjarit2Ploychompoo Yoosabai3Wittaya Panvongsa4Sirapope Wongniam5Apichart Suksamrarn6Pawinee Piyachaturawat7Usanarat Anurathapan8Suparerk Borwornpinyo9Arthit Chairoungdua10Suradej Hongeng11Kanit Bhukhai12Department of Physiology, Faculty of Science, Mahidol University, Bangkok, ThailandDepartment of Physiology, Faculty of Science, Mahidol University, Bangkok, ThailandGraduate Program in Nutrition, Faculty of Medicine Ramathibodi Hospital, Mahidol University, ThailandDepartment of Biotechnology, Faculty of Science, Mahidol University, Bangkok, ThailandToxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, ThailandCentral Instrument Facility Unit, Faculty of Science, Mahidol University, Bangkok, ThailandDepartment of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, ThailandDepartment of Physiology, Faculty of Science, Mahidol University, Bangkok, ThailandDepartment of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandDepartment of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery, Mahidol University, Bangkok, ThailandDepartment of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery, Mahidol University, Bangkok, ThailandDepartment of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; Excellent Center for Drug Discovery, Mahidol University, Bangkok, Thailand; Correspondence to: Department of Pediatrics Faculty of Medicine Ramathibodi Hospital, Mahidol University, Rama 6Rd., Ratchathewi, Bangkok 10400, Thailand.Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; Correspondence to: Department of Physiology Faculty of Science, Mahidol University, Rama 6Rd., Ratchathewi, Bangkok 10400, Thailand.Hematopoietic stem cells (HSCs, CD34+ cells) have shown therapeutic efficacy for transplantation in various hematological disorders. However, a large quantity of HSCs is required for transplantation. Therefore, strategies to increase HSC numbers and preserve HSC functions through ex vivo culture are critically required. Here, we report that expansion medium supplemented with ASPP 049, a diarylheptanoid isolated from Curcuma comosa, and a cocktail of cytokines markedly increased numbers of adult CD34+ cells. Interestingly, phenotypically defined primitive HSCs (CD34+CD38-CD90+) were significantly increased under ASPP 049 treatment relative to control. ASPP 049 treatment also improved two functional properties of HSCs, as evidenced by an increased number of CD34+CD38- cells in secondary culture (self-renewal) and the growth of colony-forming units as assessed by colony formation assay (multilineage differentiation). Transplantation of cultured CD34+ cells into immunodeficient mice demonstrated the long-term reconstitution and differentiation ability of ASPP 049-expanded cells. RNA sequencing and KEGG analysis revealed that Hippo signaling was the most likely pathway involved in the effects of ASPP 049. These results suggest that ASPP 049 improved ex vivo expansion and functional preservation of expanded HSCs. Our findings provide a rationale for the use of ASPP 049 to grow HSCs prior to hematological disease treatment.http://www.sciencedirect.com/science/article/pii/S0753332221008866Hematopoietic stem cells (HSCs)Ex vivo expansionPrimitive HSCsRepopulating HSCsDiarylheptanoid |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nopmullee Tanhuad Umnuaychoke Thongsa-ad Nareerat Sutjarit Ploychompoo Yoosabai Wittaya Panvongsa Sirapope Wongniam Apichart Suksamrarn Pawinee Piyachaturawat Usanarat Anurathapan Suparerk Borwornpinyo Arthit Chairoungdua Suradej Hongeng Kanit Bhukhai |
spellingShingle |
Nopmullee Tanhuad Umnuaychoke Thongsa-ad Nareerat Sutjarit Ploychompoo Yoosabai Wittaya Panvongsa Sirapope Wongniam Apichart Suksamrarn Pawinee Piyachaturawat Usanarat Anurathapan Suparerk Borwornpinyo Arthit Chairoungdua Suradej Hongeng Kanit Bhukhai Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa Biomedicine & Pharmacotherapy Hematopoietic stem cells (HSCs) Ex vivo expansion Primitive HSCs Repopulating HSCs Diarylheptanoid |
author_facet |
Nopmullee Tanhuad Umnuaychoke Thongsa-ad Nareerat Sutjarit Ploychompoo Yoosabai Wittaya Panvongsa Sirapope Wongniam Apichart Suksamrarn Pawinee Piyachaturawat Usanarat Anurathapan Suparerk Borwornpinyo Arthit Chairoungdua Suradej Hongeng Kanit Bhukhai |
author_sort |
Nopmullee Tanhuad |
title |
Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa |
title_short |
Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa |
title_full |
Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa |
title_fullStr |
Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa |
title_full_unstemmed |
Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa |
title_sort |
ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from curcuma comosa |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2021-11-01 |
description |
Hematopoietic stem cells (HSCs, CD34+ cells) have shown therapeutic efficacy for transplantation in various hematological disorders. However, a large quantity of HSCs is required for transplantation. Therefore, strategies to increase HSC numbers and preserve HSC functions through ex vivo culture are critically required. Here, we report that expansion medium supplemented with ASPP 049, a diarylheptanoid isolated from Curcuma comosa, and a cocktail of cytokines markedly increased numbers of adult CD34+ cells. Interestingly, phenotypically defined primitive HSCs (CD34+CD38-CD90+) were significantly increased under ASPP 049 treatment relative to control. ASPP 049 treatment also improved two functional properties of HSCs, as evidenced by an increased number of CD34+CD38- cells in secondary culture (self-renewal) and the growth of colony-forming units as assessed by colony formation assay (multilineage differentiation). Transplantation of cultured CD34+ cells into immunodeficient mice demonstrated the long-term reconstitution and differentiation ability of ASPP 049-expanded cells. RNA sequencing and KEGG analysis revealed that Hippo signaling was the most likely pathway involved in the effects of ASPP 049. These results suggest that ASPP 049 improved ex vivo expansion and functional preservation of expanded HSCs. Our findings provide a rationale for the use of ASPP 049 to grow HSCs prior to hematological disease treatment. |
topic |
Hematopoietic stem cells (HSCs) Ex vivo expansion Primitive HSCs Repopulating HSCs Diarylheptanoid |
url |
http://www.sciencedirect.com/science/article/pii/S0753332221008866 |
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