title: Effect of Tianshengyuan-1 (TSY-1) on telomerase activity and hematopoietic recovery - in vitro, ex vivo, and in vivo studies.
abstract: Aplastic anemia is a heterogeneous disorder of bone marrow failure syndrome. Accumulating evidence indicates that both acquired and congenital aplastic anemia is linked to telomerase activity and telomere length. Chinese herbal medicine Tianshengyuan-1 (TSY-1), a liquid extraction of multiple Chinese herbs, appears to stimulate hematopoiesis in patients with bone marrow deficiencies; however, the exact mechanism of action remains unclear. In this study, we investigated the effect of TSY-1 on telomere length and telomerase activity. We first investigated the effects of TSY on in vitro cultured cell lines including CD34+ hepatic stem cells and CD4+/CD8- Jurkat cells. An immune-mediated murine aplastic anemia model and human samples, including peripheral blood samples of 4 healthy donors and bone marrow hematopoietic cells from 4 patients with hypocellular myelodysplastic syndrome (MDS), were also used to test the efficacy of TSY on hematopoiesis, telomerase activity and telomere length. Our results indicated that TSY-1 increased the telomerase activity and telomere length in a dose-response manner in vitro, in vivo, and in human samples including 3 of 4 healthy individuals and 3 of 4 bone marrow samples from MDS patients. In immune-mediated murine aplastic anemia model, TSY-1 activity on Telomere length was parallel to the significant increasing of the RBC, hemoglobin, hematocrit, and platelet count in peripheral blood, increasing of CD34+ cell count and hematopoiesis, and decreasing of fatty infiltration in bone marrow samples. Our study demonstrated that TSY-1 may exert its effects by modulating telomerase activity of hematopoietic cells. Further studies are warranted to explore the precise molecular mechanisms of how TSY-1 regulates telomerase activity and telomere length, and also to test the TSY-1 in randomized control trials.
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA ; Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University and Tianjin Medical University Cancer Institute and Hospital Tianjin, China.
authors.forename: Su
authors.initials: S
authors.lastname: Lu
authors.affiliation: Beijing Tianyuyiming Biological Technology Co., Ltd (BTBTL) Beijing, China.
authors.forename: Xiaotian
authors.initials: X
authors.lastname: Qin
authors.affiliation: Institute of Materia Madica, Chinese Academy of Medical Sciencese Beijing, China.
authors.forename: Shaopeng
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Beijing Tianyuyiming Biological Technology Co., Ltd (BTBTL) Beijing, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA ; Department of Surgery, Cancer Hospital, Chinese Academy of Medical Science Beijing, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Urology, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zeng
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Yen
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Tracie
authors.initials: T
authors.lastname: Dang
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Sophie
authors.initials: S
authors.lastname: Song
authors.affiliation: Institute of Materia Madica, Chinese Academy of Medical Sciencese Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Hou
authors.affiliation: Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California at Los Angeles Los Angeles, CA, USA.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
keywords: TSY-1; hematopoietic cells; telomerase; telomere
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