G-CSF-induced myeloid cells stimulated by TLR2 enhance engraftment after allogeneic hematopoietic stem cell transplantation

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• 作者：Won-Sik Lee^a ; ¹ ; Young-Don Joo^b ; ¹ ; Kyeong-Hee Oh^c ; Hae-Jeong Won^c ; Sun-Mi Lee^c ; Moon-Young Choi^a ; Gi-Ho Han^d ; Sae-Gwang Park^c ; Il-Whan Choi^c ; Inhack Choi^c ; ^e ; Su-Kil Seo^c ; ^e ; ^{sseo@inje.ac.kr}
• 关键词：G-CSF ; Peripheral blood stem cell transplantation ; Engraftment ; Myeloid cells ; TLR2
• 刊名：Immunology Letters
• 出版年：2012
• 期刊代码：115_01652478
• 类别：med
• 出版时间：30 April, 2012
• 卷：143
• 期：2
• 页码：177-183
• 文件大小：871 K

摘要

A high frequency of G-CSF-mobilized myeloid cells (gMCs) in a donor graft accelerates hematopoietic recovery after peripheral blood stem cell transplantation (PBSCT). However, because of the limited functional efficacy of gMCs, repeated transfusions of gMCs are frequently required. In this study, we investigated a strategy to improve the functional capacity of gMCs during hematopoietic engraftment after allogeneic transplantation. We found that toll-like receptor 2 (TLR2) is constitutively expressed on gMCs. Treating gMCs with the synthetic TLR2 ligand Pam₃CSK₄ (PAM) dramatically enhanced IL-10 and TNF-伪 production. However, PAM treatment does not induce substantial cellular maturation. Moreover, PAM treatment significantly improved gMC survival. PAM treated gMCs significantly promoted myeloid differentiation of donor hematopoietic stem cells (HSCs), resulting in accelerated engraftment after allogeneic transplantation. Our data suggest that TLR2-stimulated gMCs may be a novel cellular therapeutic for increasing the efficiency of allogeneic hematopoietic stem cell transplantation (HSCT) by reducing infectious complications associated with delayed engraftment.