StemRegenin 1 (SR1) is a potent aromatic hydrocarbon receptor (AhR) antagonist (IC50 = 127nM) [1]. StemRegenin 1 promotes the self-renewal of human CD34⁺ hematopoietic stem cells (HSCs/HSPCs) by inhibiting aromatic receptors, and can also promote the differentiation of pluripotent stem cells (iPSCs) into hematogenous progenitor cells [2-3]. StemRegenin 1 can serve as a potential mitigator for radiation-induced hematopoietic system damage [4].
In multipotent hematopoietic progenitors, High-dose StemRegenin 1 (1-10µM; 7d) inhibits cell proliferation [5]. In human endothelial progenitor cells, StemRegenin 1 (1µM; 48h) delays endothelial progenitor cell senescence by regulating AhR pathway-mediated CYP1A1 and ROS generation [6].
In lethally irradiated mice model, treatment with StemRegenin 1 (30µg/kg; ip; 30d) significantly reduces mortality from total body irradiation [7]. In ovariectomized-induced bone loss mouse model, StemRegenin 1 (2.5mg/kg; ip; 42d) inhibits ovariectomy-induced bone loss in vivo [8].
References:
[1]. Boitano A E, Wang J, Romeo R, et al. Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells[J]. Science, 2010, 329(5997): 1345-1348.
[2]. Kanashiro M A, Paul S K, Sone M, et al. iPSC-Derived Mesenchymal Stem Cells Supports the Ex Vivo expansion of Human Hematopoietic Stem and Progenitor Cells Via Sterile Inflammation Pathway[J]. Blood, 2023, 142: 2680.
[3]. Singh J, Chen E L Y, Xing Y, et al. Generation and function of progenitor T cells from StemRegenin-1–expanded CD34+ human hematopoietic progenitor cells[J]. Blood advances, 2019, 3(20): 2934-2948.
[4]. Guan D, Yang Y, Pang M, et al. Indole-3-carboxaldehyde ameliorates ionizing radiation-induced hematopoietic injury by enhancing hematopoietic stem and progenitor cell quiescence[J]. Molecular and cellular biochemistry, 2024, 479(2): 313-323.
[5]. Tao L, Togarrati P P, Choi K D, et al. StemRegenin 1 selectively promotes expansion of multipotent hematopoietic progenitors derived from human embryonic stem cells[J]. Journal of Stem Cells & Regenerative Medicine, 2017, 13(2): 75.
[6]. Lim H J, Jang W B, Rethineswaran V K, et al. StemRegenin-1 attenuates endothelial progenitor cell senescence by regulating the AhR pathway-mediated CYP1A1 and ROS generation[J]. Cells, 2023, 12(15): 2005.
[7]. Hwang Y J, Shin D Y, Kim M J, et al. StemRegenin 1 mitigates radiation-mediated hematopoietic injury by modulating radioresponse of hematopoietic stem/progenitor cells[J]. Biomedicines, 2023, 11(3): 824.
[8]. Zhou S, Li J, Ying T, et al. StemRegenin 1 attenuates the RANKL-induced osteoclastogenesis via inhibiting AhR-c-src-NF-κB/p-ERK MAPK-NFATc1 signaling pathway[J]. Iscience, 2024, 27(5).
StemRegenin 1 (SR1)是一种强效芳香烃受体（AhR）拮抗剂（IC50 = 127nM） [1]。StemRegenin 1通过抑制芳香烃受体促进人类CD34⁺造血干细胞（HSC/HSPC）的自我更新，并能促进多能干细胞（iPSC）分化为造血祖细胞 [2-3]。StemRegenin 1可作为缓解辐射诱导的造血系统损伤的潜在药物 [4]。
在多能造血祖细胞中，高剂量StemRegenin 1（1-10µM；7d）可抑制细胞增殖 [5]。在人类内皮祖细胞中，StemRegenin 1（1µM；48h）通过调节AhR通路介导的CYP1A1和ROS生成来延缓内皮祖细胞衰老 [6]。
在致死性辐射小鼠模型中，StemRegenin 1（30µg/kg；ip；30d）治疗显著降低了全身辐射造成的死亡率 [7]。在卵巢切除诱发的骨质疏松小鼠模型中，StemRegenin 1（2.5mg/kg；ip；42d）可抑制卵巢切除诱发的体内骨质疏松 [8]。