Communication of substance P, calcitonin-gene-related neuropeptides and chemokine receptor 4 (CXCR4) in cord blood hematopoietic stem cells

Shahrokhi, Somayeh; Ebtekar, Massoumeh; Alimoghaddam, Kamran; Sharifi, Zohreh; Ghaffari, Seyed Hamidolah; Pourfathollah, Ali Akbar; Kheirandish, Maryam; Mohseni, Mahboobeh; Ghavamzadeh, Ardeshir

doi:10.1016/j.npep.2010.06.002

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Volume 44, Issue 5 , Pages 385-389, October 2010

Communication of substance P, calcitonin-gene-related neuropeptides and chemokine receptor 4 (CXCR4) in cord blood hematopoietic stem cells

Somayeh Shahrokhi
- Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Massoumeh Ebtekar
- Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
- Corresponding author. Address: Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran, Iran. Tel./fax: +98 21 8288 3891.
Kamran Alimoghaddam
- Hematology, Oncology and Stem Cell Transplantation Research Center of Tehran University of Medical Sciences, Iran
- Cord Blood Bank of Iran, Tehran University of Medical Sciences, Iran
- Corresponding author at: Hematology, Oncology and Stem Cell Transplantation Research Center of Tehran University of Medical Sciences, P.O. Box 14114, Tehran, Iran. Tel.: +98 21 8490 2626; fax: +98 21 8800 4140.
Zohreh Sharifi
- Research Center, Department of Virology, Iranian Blood Transfusion Organization, Tehran, Iran
Seyed Hamidolah Ghaffari
- Hematology, Oncology and Stem Cell Transplantation Research Center of Tehran University of Medical Sciences, Iran
Ali Akbar Pourfathollah
- Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Maryam Kheirandish
- Research Center, Department of Immunology, Iranian Blood Transfusion Organization, Tehran, Iran
Mahboobeh Mohseni
- Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
Ardeshir Ghavamzadeh
- Hematology, Oncology and Stem Cell Transplantation Research Center of Tehran University of Medical Sciences, Iran

Received 5 April 2010; accepted 11 June 2010. published online 05 July 2010.

Abstract

Background

Modulation of the expression of CXCR4 as a critical adhesion molecule on cord blood (CB) CD34⁺ cells could overcome delay following cord blood transplantation. Identification of beneficial effects of growth factors including cytokines and neuropeptides on CXCR4 expression would enable our understanding of this complicated network. Therefore, we aimed to assess the role of substance P (SP) and Calcitonin gene related peptide (CGRP) on CXCR4 levels.

Material and methods

CD34⁺cells purified from CB were cultured in a serum-free liquid culture system. Different concentrations of SP and CGRP were used in combination with cytokine cocktail. Expression of CXCR4 at protein and genomic levels was assessed by flow cytometry and real time RT-PCR.

Results

Our results indicate increased CXCR4⁺ CD34⁺ cells after 7days cultivation with SP and/or CGRP. Increased gene expression of the CXCR4 molecule was observed at 10⁻⁹M either SP or CGRP individually, by day 11 as compared to control group.

Conclusions

Our study indicates that SP and CGRP induce CXCR4 protein expression in short term culture, and stimulate its expression. Consequently, the increased expression of CXCR4 could improve engraftment of CB CD34⁺ cells.

Keywords: CGRP, CXCR4, SP, Stem cell