Mesenchymal Stem Cell-Derived Microvesicles Support Ex Vivo Expansion of Cord Blood-Derived CD34(+) Cells.

Hui Xie,Liming Zhang,Ping Zou,Aiqi Zhao,Li Sun,Li Chen,Hongxiang Wang,Teng Liu,An-Yuan Guo,Qiubai Li,Qian Lei,Zhichao Chen,Fei Gao

doi:10.1155/2016/6493241

Abstract

Mesenchymal stem cells (MSCs) are known to support the characteristic properties of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow hematopoietic microenvironment. MSCs are used in coculture systems as a feeder layer for the ex vivo expansion of umbilical cord blood (CB) to increase the relatively low number of HSPCs in CB. Findings increasingly suggest that MSC-derived microvesicles (MSC-MVs) play an important role in the biological functions of their parent cells. We speculate that MSC-MVs may recapitulate the hematopoiesis-supporting effects of their parent cells. In the current study, we found MSC-MVs containing microRNAs that are involved in the regulation of hematopoiesis. We also demonstrated that MSC-MVs could improve the expansion of CB-derived mononuclear cells and CD34+ cells and generate a greater number of primitive progenitor cells in vitro. Additionally, when MSC-MVs were added to the CB-MSC coculture system, they could improve the hematopoiesis-supporting effects of MSCs. These findings highlight the role of MSC-MVs in the ex vivo expansion of CB, which may offer a promising therapeutic approach in CB transplantation.

Highlights

Hematopoietic stem cell transplantation (HSCT) has become a common procedure in the treatment of malignant hematologic diseases [1]
Assuming that Mesenchymal stem cells (MSCs)-MVs may mimic the hematopoiesis-supporting effects of MSCs, we investigated whether MSC-derived microvesicles (MSC-MVs) could improve the ex vivo expansion of cord blood (CB)
These results suggest that MSC-MVs may be one of the cues provided in vivo by MSCs in the hematopoietic microenvironment that help to maintain the characteristic functional properties of hematopoietic stem and progenitor cells (HSPCs)

Summary

Introduction

Hematopoietic stem cell transplantation (HSCT) has become a common procedure in the treatment of malignant hematologic diseases [1]. Compared with bone marrow or mobilized peripheral blood progenitor cells from adult donors, umbilical cord blood (CB) has emerged as an attractive source of hematopoietic stem and progenitor cells (HSPCs) for HSCT. They have several advantages, such as easy acquisition, ready availability, and reduced incidence and severity of graft versus host disease as well as less stringent requirements for human leukocyte antigen matches between donor and recipient [2]. This is thought to be the main reason for the delayed neutrophil and platelet engraftment and the high risk of engraftment failure, which are often associated with CB transplantation [4] To overcome this limitation, substantial effort has been dedicated to developing strategies to increase the number of HSPCs in CB prior to infusion. Researchers used MSCs as a feeder layer for the

Methods

Results

Conclusion