Recombinant human thrombopoietin promotes hematopoietic reconstruction after severe whole body irradiation.

Chao Wang,Sihan Wang,Yang Lv,Xuetao Pei,Jingxue Wang,Lin Chen,Huanzhang Xia,Lijuan He,Zeng Fan,Yiming Liu,Yanhua Li,Bowen Zhang,Xiuyuan Zhang,Jing Zhang

doi:10.1038/srep12993

Abstract

Recombinant human thrombopoietin (rHuTPO) is a drug that is used clinically to promote megakaryocyte and platelet generation. Here, we report the mitigative effect of rHuTPO (administered after exposure) against severe whole body irradiation in mice. Injection of rHuTPO for 14 consecutive days following exposure significantly improved the survival rate of lethally irradiated mice. RHuTPO treatment notably increased bone marrow cell density and LSK cell numbers in the mice after sub-lethal irradiation primarily by promoting residual HSC proliferation. In lethally irradiated mice with hematopoietic cell transplantation, rHuTPO treatment increased the survival rate and enhanced hematopoietic cell engraftment compared with the placebo treatment. Our observations indicate that recombinant human TPO might have a therapeutic role in promoting hematopoietic reconstitution and HSC engraftment.

Highlights

TPO is an important regulator and clinical drug for promoting megakaryopoiesis and platelet production[21,22]
We initially selected the survival rate criteria to evaluate the effectiveness of Recombinant human thrombopoietin (rHuTPO) in alleviating injury to the hematopoietic system and other tissues following radiation
All of the irradiated mice that received PBS injections died within 17 days (Fig. 1A), which indicated that consecutive injections of rHuTPO were effective in elevating the survival rates of the mice following severe whole body irradiation

Summary

Introduction

TPO is an important regulator and clinical drug for promoting megakaryopoiesis and platelet production[21,22]. The interaction of TPO with its receptor MPL exhibits important roles in hematopoiesis, HSC self-renewal and quiescence[23,24,25,26] Both TPO and MPL knockout mice display reduced numbers of HSCs in the bone marrow, significantly fewer megakaryocytes and platelets[27,28], and exogenous TPO transiently increases the proportions of quiescent HSCs in the niche[29]. These data further support the role of TPO in hematopoietic recovery[30]. Our observations indicate that rHuTPO might have a therapeutic role in promoting HSPC regeneration and hematopoietic reconstitution

Methods

Results

Discussion

Conclusion