Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa

Tanhuad, Nopmullee; Thongsa-ad, Umnuaychoke; Sutjarit, Nareerat; Yoosabai, Ploychompoo; Panvongsa, Wittaya; Wongniam, Sirapope; Suksamrarn, Apichart; Piyachaturawat, Pawinee; Anurathapan, Usanarat; Borwornpinyo, Suparerk; Chairoungdua, Arthit; Hongeng, Suradej; Bhukhai, Kanit

doi:10.1016/j.biopha.2021.112102

Cited by 5 publications

(7 citation statements)

References 52 publications

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“…Unexpectedly, they also participate in the Hippo signaling pathway (Additional file 1 : Fig. S5D, Table S5), which has been consistently shown to play a role in the effect of ASPP 049 on expanded HSCs, as previously described [ 29 ]. The gene sets identified, consisting of 46 DEGs and 11 genes of interest, were analyzed using KEGG for signaling pathway predictions related to the rescue effects of ASPP 049 on mRNA profiles (Additional file 1 : Fig.…”

Section: Resultssupporting

confidence: 61%

“…Previous studies have revealed the constructive effects of ASPP 049, a diarylheptanoid isolated from Curcuma comosa [ 27 , 28 ], on an ex vivo CD34 + CD38 − CD90 + human HSC-culturing system. This compound potentially induces the cultured HSCs to have multi-lineage differentiation abilities in vitro, long-term reconstitution in vivo [ 29 ], as well as hematopoiesis improvement in an anemic mouse model [ 30 ]. However, the potential of HSC derivation from hiPSCs has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

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Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative

Thongsa-ad,

Wongpan,

Wongkummool

et al. 2024

Stem Cell Res Ther

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Background The diarylheptanoid ASPP 049 has improved the quality of adult hematopoietic stem cell (HSC) expansion ex vivo through long-term reconstitution in animal models. However, its effect on hematopoietic regeneration from human induced pluripotent stem cells (hiPSCs) is unknown. Method We utilized a defined cocktail of cytokines without serum or feeder followed by the supplementation of ASPP 049 to produce hematopoietic stem/progenitor cells (HSPCs). Flow cytometry and trypan blue exclusion analysis were used to identify nonadherent and adherent cells. Nonadherent cells were harvested to investigate the effect of ASPP 049 on multipotency using LTC-IC and CFU assays. Subsequently, the mechanism of action was explored through transcriptomic profiles, which were validated by qRT-PCR, immunoblotting, and immunofluorescence analysis. Result The supplementation of ASPP 049 increased the number of phenotypically defined primitive HSPCs (CD34+CD45+CD90+) two-fold relative to seeded hiPSC colonies, indicating enhanced HSC derivation from hiPSCs. Under ASPP 049-supplemented conditions, we observed elevated HSPC niches, including CD144+CD73− hemogenic- and CD144+CD73+ vascular-endothelial progenitors, during HSC differentiation. Moreover, harvested ASPP 049-treated cells exhibited improved self-renewal and a significantly larger proportion of different blood cell colonies with unbiased lineages, indicating enhanced HSC stemness properties. Transcriptomics and KEGG analysis of sorted CD34+CD45+ cells-related mRNA profiles revealed that the Hippo signaling pathway is the most significant in responding to WWTR1/TAZ, which correlates with the validation of the protein expression. Interestingly, ASPP 049-supplemented HSPCs upregulated 11 genes similarly to umbilical cord blood-derived HSPCs. Conclusion These findings suggest that ASPP 049 can improve HSC-generating protocols with proliferative potentials, self-renewal ability, unbiased differentiation, and a definable mechanism of action for the clinical perspective of hematopoietic regenerative medicine. Graphical abstract

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Section: Resultssupporting

confidence: 61%

Section: Introductionmentioning

confidence: 99%

Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative

Thongsa-ad,

Wongpan,

Wongkummool

et al. 2024

Stem Cell Res Ther

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“… Target/signaling Expansion effect Ref. Rapamycin mTOR ‒ 112 Garcinol/isogarcinol HATs 4.5-/7.4-fold HSCs 2.5-fold SRCs (garcinol) 118 TSA HDAC 2.5-fold CD34 + 40-fold CD34 + CD90 + 132 EchA ROS inhibition PI3K/AKT activation 1.33-fold CD34 + 1.7-fold CFUs 137 ASPP049 Hippo signaling ∼1.5-fold CD34 + CD38 − ∼2-fold hCD45 + 143 Chrysin p19, p57, MNDA, NR4A2, HOXB4 ∼1.5-fold HSCs 2.7-fold SRCs 145 Resveratol ‒ 1.84-fold CD34 + /CD133 + 138 , 139 , 140 CAPE HIF-1 α , SDF-1 α and VEGF-A 1.47-fold CFUs 1.77-fold SRCs 141 , 142 5-HT Apoptosis inhibition 1.73-fold CFU-F 12.2-fold CD34 + 146 α -Tocopherol ERK1/2 2-fold LSKs 147 ATRA RA receptor 4-fold CFUs 148 , 149 …”

Section: Small Molecules For Ex Vivo Hsc Expansionmentioning

confidence: 99%

“…Recently, researchers from Thailand reported a diarylheptanoid compound ASPP 049 ( 61 ) isolated from Curcuma comosa with ex vivo expansion activity and repopulating capacity in vivo 143 . RNA-seq analysis of expanded HSCs suggested Hippo pathway was most affected.…”

Section: Small Molecules For Ex Vivo Hsc Expansionmentioning

confidence: 99%

Development and clinical advancement of small molecules for ex vivo expansion of hematopoietic stem cell

Wang

Ding

et al. 2022

Acta Pharmaceutica Sinica B

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“…Previous phytochemical investigations of this plant revealed the presence of a rich source of diarylheptanoids [24]. Moreover, it has also been reported for various pharmacological activities including lipid-lowering, anti-adipogenic, bone sparing in ovariectomized rats, enhancing the expansion of hematopoietic stem cells for treatment of hematological disorders, antioxidant and anti-inflammatory activities [25][26][27][28][29][30][31].…”

Section: Introductionmentioning

confidence: 95%

Curcuma aromatica and Curcuma comosa Extracts and Isolated Constituents Provide Protection against UVB-Induced Damage and Attenuate Matrix Metalloproteinase-1 Expression in HaCaT Cells

et al. 2022

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Ultraviolet-B (UVB) exposure is one of the primary extrinsic factors causing skin photoaging. It stimulates inflammatory responses and arrests the cell cycle. Matrix metalloproteinase-1 (MMP-1) secreted by keratinocytes is one of the important extracellular matrixes to attenuate UVB-induced skin aging via collagen degradation. Curcuma aromatica (CA) and Curcuma comosa (CC), the herbaceous plants in the Zingiberaceae family, are commonly used in Thai traditional women’s medicines. The present work was aimed to investigate the potential of the CA and CC extracts and their isolated compounds to attenuate UVB-induced MMP-1 and cell cycle arrest in HaCaT keratinocytes. Total phenolic contents and antioxidant capacities of the extracts were determined. CC extract contains more phenolic components and provides more potent antioxidant activities than CA extract. HaCaTs were pretreated with the extracts or their isolated constituents 1–4 for 24 h and then repeatedly exposed to UVB at 100 mJ/cm2 10 times. Both extracts and compounds 1–4 effectively reduce UVB-induced MMP-1 levels in HaCaT cells and restore cell cycle arrest. This is the first report on the potential of CA and CC extracts in reducing UVB-induced MMP-1 expression and regulating cell proliferation in HaCaT cells. Thus, CA and CC extracts might be used as alternative natural agents to prevent UVB-induced skin photoaging.

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Ex vivo expansion and functional activity preservation of adult hematopoietic stem cells by a diarylheptanoid from Curcuma comosa

Cited by 5 publications

References 52 publications

Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative

Improving hematopoietic differentiation from human induced pluripotent stem cells by the modulation of Hippo signaling with a diarylheptanoid derivative

Development and clinical advancement of small molecules for ex vivo expansion of hematopoietic stem cell

Curcuma aromatica and Curcuma comosa Extracts and Isolated Constituents Provide Protection against UVB-Induced Damage and Attenuate Matrix Metalloproteinase-1 Expression in HaCaT Cells

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