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Adv Pharm Bull. 2020;10(2): 315-322.
doi: 10.34172/apb.2020.038
PMID: 32373502
PMCID: PMC7191234
Scopus ID: 85088695505
  Abstract View: 535
  PDF Download: 329

Research Article

Effect of Mesenchymal Stem Cell-derived Microvesicles on Megakaryocytic Differentiation of CD34+ Hematopoietic Stem Cells

Sara Aqmasheh 1 ORCID logo, Karim Shamsasenjan 1* ORCID logo, Elham Khalaf Adeli 2, Aliakbar Movassaghpourakbari 3, Parvin Akbarzadehlaleh 4, Davod Pashoutan Sarvar 5 ORCID logo, Hamzeh Timari 1

1 Umbilical Cord Blood Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
2 Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran.
3 Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
4 Department of Pharmaceutical Biotechnology, Tabriz University of Medical Science, Tabriz, Iran.
5 Asadabad School of Medical Sciences, Asadabad, Iran.v
*Corresponding Author: Karim Shamsasenjan, Tel: +98 41 33824536, Fax: +98 41 33824536, Email: k.shams@ibto.ir

Abstract

Purpose: Mesenchymal stem cells (MSCs) release hematopoietic cytokines, growth factors, and Microvesicles (MVs) supporting the hematopoietic stem cells (HSCs). MVs released from various cells, playing a crucial role in biological functions of their parental cells. MSC-derived MVs contain microRNAs and proteins with key roles in the regulation of hematopoiesis. Umbilical cord blood (UCB) is a source for transplantation but the long-term recovery of platelets is a main problem. Therefore, we intend to show that MSC-MVs are able to improve the differentiation of UCB-derived CD34+ cells to megakaryocyte lineage.

Methods: In this descriptive study, MSCs were cultured in DMEM to collect the culture supernatant, which was ultracentrifuged for the isolation of MVs. HSCs were isolated from UCB using MACS method and cultured in IMDM supplemented with cytokines and MVs in three different conditions. Megakaryocyte differentiation was evaluated through the expression of specific markers and genes after 72 hours, and the data was analyzed by t test (P<0.05).

Results: The expression of specific megakaryocyte markers (CD41 and CD61) in the presence of different concentrations of MSC-MVs did not show any significant difference. Also, the expression of specific genes of megakaryocyte lineage was compared with control group. The expression of GATA2 and c-Mpl was significantly increased, GATA1 was not significantly decreased, and FLI1 was significantly decreased.

Conclusion: MSC-MVs could improve the expression of specific megakaryocyte genes; however, there was no significant expression of CD markers. Further studies, including the evaluation of late stages of megakaryocyte differentiation, are required to evaluate platelet production and shedding

Keywords: Microvesicle, Hematopoietic stem/ progenitor cells, Mesenchymal stem cells, Megakaryocyte
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Submitted: 13 May 2019
Revision: 22 Aug 2019
Accepted: 30 Sep 2019
ePublished: 18 Feb 2020
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