Study on the mechanism of enhancing homing efficiency of human hematopoietic stem/progenitor cells into bone marrow after manipulation with tumor necrosis factor alpha in xenotransplanted BALB/c mouse model.
- Author:
Hong-sheng DAI
1
;
Jing-tao GAO
;
Tong-wen ZHANG
;
Zhou YANG
;
Yong-zhe CHE
;
Yi-zhou ZHENG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Antigens, CD34; Bone Marrow; Cell Movement; Cell Separation; Chemokine CXCL12; metabolism; Female; Fetal Blood; cytology; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; drug effects; immunology; metabolism; Humans; Mice; Mice, Inbred BALB C; Receptors, CXCR4; metabolism; Transplantation Conditioning; Transplantation, Heterologous; Tumor Necrosis Factor-alpha; pharmacology
- From: Chinese Journal of Hematology 2009;30(2):97-102
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the role of tumor necrosis factor (TNF) alpha on the homing efficiency of hematopoietic stem/progenitor cells (HS/PC) into bone marrow and its mechanism.
METHODSCFSE-labeled umbilical cord blood (UCB) CD34+ cells were transplanted into irradiated (control group) or combined with TNF alpha prepared (experimental group) BALB/c recipient mice. The distribution in peripheral blood, liver, lung and homing characteristics in bone marrow and spleen of UCB CD34+ cells, in BALB/c recipient mice were determined 20 hours after xenotransplantation by flow cytometry (FACS) and their homing efficiency was calculated. ELISA was used to measure serum SDF-1 alpha level. CXCR4 expression levels of on UCB CD34+ cells were assessed by FACS pre-/post-manipulation with TNF alpha. SDF-1 alpha expression level in bone marrow and spleen was tested by immunohistochemistry.
RESULTSUCB CD34+ cells mainly home into recipient mice bone marrow and spleen; The homing efficiency in experimental group bone marrow [(0.65 +/- 0.13)%] was significantly higher than that in control ones [(0.30 +/- 0.09)%, P < 0.01], whereas the homing efficiency in experimental group spleen was dramatically lower than that in control ones (P < 0.01); Treatment with TNF alpha did not affect recipient serum SDF-1 alpha level; After 18 hours co-cultured with TNF alpha, the CXCR4e expression level on UCB CD34+ cells was similar to that on fresh ones; TNF alpha treatment induced significantly higher SDF-1 alpha expression on osteoblastic and stromal cells in bone marrow, and reversed spleen SDF-1 alpha gradient that was originally favorable for CD34+ cells homing.
CONCLUSIONTNF alpha enhances the homing efficiency of HS/PC via up-regulating SDF-1 alpha gradient in bone marrow, and might be an useful enhancer for HS/PC homing in clinical practice.
