StemRegenin 1

芳烃受体(AHR)拮抗剂

产品号 #(选择产品)

产品号 #72342_C

芳烃受体(AHR)拮抗剂

总览

StemRegenin1 (SR1) 是芳烃受体 (AHR) 的拮抗剂。它能够促进 CD34+ 人造血干细胞体外扩增,并促进非人灵长类动物诱导多能干细胞生成 CD34+ 造血祖细胞。SR1 已被证明可与 UM729 协同作用,在培养中阻止急性髓性白血病(AML)细胞的分化。SR1 还能刺激 CD34+ 造血祖细胞增殖并分化为树突状细胞。

维持和自我更新
·促进培养的人造血干细胞的维持和扩增(Boitano et al., Csaszar et al.)。

分化
·刺激CD34+造血祖细胞分化为功能性人树突状细胞(Thordardottir et al.)。
促进诱导多能干细胞(iPS)的造血分化。(Gori et al.)。

癌症研究
·与UM729协同作用,抑制培养的 AML 细胞分化(Pabst et al.)。

细胞类型
癌细胞及细胞系,树突状细胞(DCs),造血干/祖细胞,白血病/淋巴瘤细胞,多能干细胞
 
种属
人,小鼠,非人灵长类,其它细胞系,大鼠
 
应用
分化,扩增
 
研究领域
癌症,干细胞生物学
 
CAS 编号
1227633-49-9
 
化学式
C₂₄H₂₃N₅OS
 
纯度
≥98%
 
通路
AHR
 
靶点
AHR
 

Protocols and Documentation

Find supporting information and directions for use in the Product Information Sheet or explore additional protocols below.

Document Type
Product Name
Catalog #
Lot #
Language
Product Name
StemRegenin 1
Catalog #
72342, 72344
Lot #
All
Language
English
Document Type
Safety Data Sheet
Product Name
StemRegenin 1
Catalog #
72342, 72344
Lot #
All
Language
English

Applications

This product is designed for use in the following research area(s) as part of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we offer to support each research area.

Resources and Publications

Educational Materials (3)

Publications (4)

The aryl hydrocarbon receptor antagonist StemRegenin 1 promotes human plasmacytoid and myeloid dendritic cell development from CD34+ hematopoietic progenitor cells. Thordardottir S et al. Stem cells and development 2014 MAY

Abstract

The superiority of dendritic cells (DCs) as antigen-presenting cells has been exploited in numerous clinical trials, where generally monocyte-derived DCs (Mo-DCs) are injected to induce immunity in patients with cancer or infectious diseases. Despite promising expansion of antigen-specific T cells, the clinical responses following vaccination have been limited, indicating that further improvements of DC vaccine potency are necessary. Pre-clinical studies suggest that vaccination with combination of primary DC subsets, such as myeloid and plasmacytoid blood DCs (mDCs and pDCs, respectively), may result in stronger clinical responses. However, it is a challenge to obtain high enough numbers of primary DCs for immunotherapy, since their frequency in blood is very low. We therefore explored the possibility to generate them from hematopoietic progenitor cells (HPCs). Here, we show that by inhibiting the aryl hydrocarbon receptor with its antagonist StemRegenin 1 (SR1), clinical-scale numbers of functional BDCA2(+)BDCA4(+) pDCs, BDCA1(+) mDCs, and BDCA3(+)DNGR1(+) mDCs can be efficiently generated from human CD34(+) HPCs. The ex vivo-generated DCs were phenotypically and functionally comparable to peripheral blood DCs. They secreted high levels of pro-inflammatory cytokines such as interferon (IFN)-α, interleukin (IL)-12, and tumor necrosis factor (TNF)-α and upregulated co-stimulatory molecules and maturation markers following stimulation with Toll-like receptor (TLR) ligands. Further, they induced potent allogeneic T-cell responses and activated antigen-experienced T cells. These findings demonstrate that SR1 can be exploited to generate high numbers of functional pDCs and mDCs from CD34(+) HPCs, providing an alternative option to Mo-DCs for immunotherapy of patients with cancer or infections.
Efficient generation, purification, and expansion of CD34(+) hematopoietic progenitor cells from nonhuman primate-induced pluripotent stem cells. Gori JL et al. Blood 2012 SEP

Abstract

Induced pluripotent stem cell (iPSC) therapeutics are a promising treatment for genetic and infectious diseases. To assess engraftment, risk of neoplastic formation, and therapeutic benefit in an autologous setting, testing iPSC therapeutics in an appropriate model, such as the pigtail macaque (Macaca nemestrina; Mn), is crucial. Here, we developed a chemically defined, scalable, and reproducible specification protocol with bone morphogenetic protein 4, prostaglandin-E2 (PGE2), and StemRegenin 1 (SR1) for hematopoietic differentiation of Mn iPSCs. Sequential coculture with bone morphogenetic protein 4, PGE2, and SR1 led to robust Mn iPSC hematopoietic progenitor cell formation. The combination of PGE2 and SR1 increased CD34(+)CD38(-)Thy1(+)CD45RA(-)CD49f(+) cell yield by 6-fold. CD34(+)CD38(-)Thy1(+)CD45RA(-)CD49f(+) cells isolated on the basis of CD34 expression and cultured in SR1 expanded 3-fold and maintained this long-term repopulating HSC phenotype. Purified CD34(high) cells exhibited 4-fold greater hematopoietic colony-forming potential compared with unsorted hematopoietic progenitors and had bilineage differentiation potential. On the basis of these studies, we calculated the cell yields that must be achieved at each stage to meet a threshold CD34(+) cell dose that is required for engraftment in the pigtail macaque. Our protocol will support scale-up and testing of iPSC-derived CD34(high) cell therapies in a clinically relevant nonhuman primate model.
Rapid expansion of human hematopoietic stem cells by automated control of inhibitory feedback signaling. Csaszar E et al. Cell stem cell 2012 FEB

Abstract

Clinical hematopoietic transplantation outcomes are strongly correlated with the numbers of cells infused. Anticipated novel therapeutic implementations of hematopoietic stem cells (HSCs) and their derivatives further increase interest in strategies to expand HSCs ex vivo. A fundamental limitation in all HSC-driven culture systems is the rapid generation of differentiating cells and their secreted inhibitory feedback signals. Herein we describe an integrated computational and experimental strategy that enables a tunable reduction in the global levels and impact of paracrine signaling factors in an automated closed-system process by employing a controlled fed-batch media dilution approach. Application of this system to human cord blood cells yielded a rapid (12-day) 11-fold increase of HSCs with self-renewing, multilineage repopulating ability. These results highlight the marked improvements that control of feedback signaling can offer primary stem cell culture and demonstrate a clinically relevant rapid and relatively low culture volume strategy for ex vivo HSC expansion.

更多信息

更多信息
Species Human, Mouse, Non-Human Primate, Other, Rat
Cas Number 1227633-49-9
Chemical Formula C₂₄H₂₃N₅OS
Purity ≥ 98%
Target AHR
Pathway AHR
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