Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential

Yizhou Zheng, Nobukazu Watanabe, Tokiko Nagamura-Inoue, Koichi Igura, Hitomi Nagayama, Arinobu Tojo, Ryuji Tanosaki, Yoichi Takaue, Shinichiro Okamoto, Tsuneo A. Takahashi

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Objective. The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. Materials and Methods. A homing-related molecule repertoire expressed on HS/PCs from fresh and cryopreserved UCB, mobilized peripheral blood (mPB), and bone marrow (BM) were compared using sensitive, four-color fluorescence-activated cell sorting analysis. Purified CD34+ cells were subjected to ex vivo transmigration through double-coated transwell filter inserts, and an in vivo homing assay was performed in xenotransplanted NOD/SCID mice. Results. UCB-derived CD34bright cells expressed significantly lower levels of CD49e, CD49f, and CXCR-4 than their mPB and BM counterparts. CD34+ cells from UCB (and BM) exhibited significantly lower ex vivo transmigration than those from mPB, which were largely blocked by neutralizing antibodies to CD49e or CD49f. Recombinant human tumor necrosis factor-α treatment enhanced ex vivo transmigration of CD34+ cells from UCB and BM by inducing expression of the matrix metalloproteinases MMP-2/MMP-9. Short-term treatment of UCB-derived CD34+ cells with rHu-stem cell factor (rHuSCF) up-regulated levels of the homing-related molecules with their increased ex vivo transmigratory and in vivo homing potential. Conclusion. Our results indicate that disadvantageous transmigratory behavior of HS/PCs from UCB, which might partly explain the delayed reconstitution after UCBT, can be reversed by ex vivo manipulation with rHuSCF.

Original languageEnglish
Pages (from-to)1237-1246
Number of pages10
JournalExperimental Hematology
Volume31
Issue number12
DOIs
Publication statusPublished - 2003 Dec

Fingerprint

Stem Cell Factor
Hematopoietic Stem Cells
Fetal Blood
Up-Regulation
Matrix Metalloproteinases
Bone Marrow Cells
Transplantation
Bone Marrow
Inbred NOD Mouse
SCID Mice
Matrix Metalloproteinase 2
Neutralizing Antibodies
Flow Cytometry
Color

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

Cite this

Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential. / Zheng, Yizhou; Watanabe, Nobukazu; Nagamura-Inoue, Tokiko; Igura, Koichi; Nagayama, Hitomi; Tojo, Arinobu; Tanosaki, Ryuji; Takaue, Yoichi; Okamoto, Shinichiro; Takahashi, Tsuneo A.

In: Experimental Hematology, Vol. 31, No. 12, 12.2003, p. 1237-1246.

Research output: Contribution to journalArticle

Zheng, Yizhou ; Watanabe, Nobukazu ; Nagamura-Inoue, Tokiko ; Igura, Koichi ; Nagayama, Hitomi ; Tojo, Arinobu ; Tanosaki, Ryuji ; Takaue, Yoichi ; Okamoto, Shinichiro ; Takahashi, Tsuneo A. / Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential. In: Experimental Hematology. 2003 ; Vol. 31, No. 12. pp. 1237-1246.
@article{63efd70d96474f009aaae25ef048d04a,
title = "Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential",
abstract = "Objective. The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. Materials and Methods. A homing-related molecule repertoire expressed on HS/PCs from fresh and cryopreserved UCB, mobilized peripheral blood (mPB), and bone marrow (BM) were compared using sensitive, four-color fluorescence-activated cell sorting analysis. Purified CD34+ cells were subjected to ex vivo transmigration through double-coated transwell filter inserts, and an in vivo homing assay was performed in xenotransplanted NOD/SCID mice. Results. UCB-derived CD34bright cells expressed significantly lower levels of CD49e, CD49f, and CXCR-4 than their mPB and BM counterparts. CD34+ cells from UCB (and BM) exhibited significantly lower ex vivo transmigration than those from mPB, which were largely blocked by neutralizing antibodies to CD49e or CD49f. Recombinant human tumor necrosis factor-α treatment enhanced ex vivo transmigration of CD34+ cells from UCB and BM by inducing expression of the matrix metalloproteinases MMP-2/MMP-9. Short-term treatment of UCB-derived CD34+ cells with rHu-stem cell factor (rHuSCF) up-regulated levels of the homing-related molecules with their increased ex vivo transmigratory and in vivo homing potential. Conclusion. Our results indicate that disadvantageous transmigratory behavior of HS/PCs from UCB, which might partly explain the delayed reconstitution after UCBT, can be reversed by ex vivo manipulation with rHuSCF.",
author = "Yizhou Zheng and Nobukazu Watanabe and Tokiko Nagamura-Inoue and Koichi Igura and Hitomi Nagayama and Arinobu Tojo and Ryuji Tanosaki and Yoichi Takaue and Shinichiro Okamoto and Takahashi, {Tsuneo A.}",
year = "2003",
month = "12",
doi = "10.1016/j.exphem.2003.08.016",
language = "English",
volume = "31",
pages = "1237--1246",
journal = "Experimental Hematology",
issn = "0301-472X",
publisher = "Elsevier Inc.",
number = "12",

}

TY - JOUR

T1 - Ex vivo manipulation of umbilical cord blood-derived hematopoietic stem/progenitor cells with recombinant human stem cell factor can up-regulate levels of homing-essential molecules to increase their transmigratory potential

AU - Zheng, Yizhou

AU - Watanabe, Nobukazu

AU - Nagamura-Inoue, Tokiko

AU - Igura, Koichi

AU - Nagayama, Hitomi

AU - Tojo, Arinobu

AU - Tanosaki, Ryuji

AU - Takaue, Yoichi

AU - Okamoto, Shinichiro

AU - Takahashi, Tsuneo A.

PY - 2003/12

Y1 - 2003/12

N2 - Objective. The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. Materials and Methods. A homing-related molecule repertoire expressed on HS/PCs from fresh and cryopreserved UCB, mobilized peripheral blood (mPB), and bone marrow (BM) were compared using sensitive, four-color fluorescence-activated cell sorting analysis. Purified CD34+ cells were subjected to ex vivo transmigration through double-coated transwell filter inserts, and an in vivo homing assay was performed in xenotransplanted NOD/SCID mice. Results. UCB-derived CD34bright cells expressed significantly lower levels of CD49e, CD49f, and CXCR-4 than their mPB and BM counterparts. CD34+ cells from UCB (and BM) exhibited significantly lower ex vivo transmigration than those from mPB, which were largely blocked by neutralizing antibodies to CD49e or CD49f. Recombinant human tumor necrosis factor-α treatment enhanced ex vivo transmigration of CD34+ cells from UCB and BM by inducing expression of the matrix metalloproteinases MMP-2/MMP-9. Short-term treatment of UCB-derived CD34+ cells with rHu-stem cell factor (rHuSCF) up-regulated levels of the homing-related molecules with their increased ex vivo transmigratory and in vivo homing potential. Conclusion. Our results indicate that disadvantageous transmigratory behavior of HS/PCs from UCB, which might partly explain the delayed reconstitution after UCBT, can be reversed by ex vivo manipulation with rHuSCF.

AB - Objective. The cause of delayed hematopoietic reconstitution after umbilical cord blood transplantation (UCBT) remains controversial. We hypothesized that hematopoietic stem/progenitor cells (HS/PCs) from UCB have some defects of the homing-related molecules responsible for their slow engraftment. Materials and Methods. A homing-related molecule repertoire expressed on HS/PCs from fresh and cryopreserved UCB, mobilized peripheral blood (mPB), and bone marrow (BM) were compared using sensitive, four-color fluorescence-activated cell sorting analysis. Purified CD34+ cells were subjected to ex vivo transmigration through double-coated transwell filter inserts, and an in vivo homing assay was performed in xenotransplanted NOD/SCID mice. Results. UCB-derived CD34bright cells expressed significantly lower levels of CD49e, CD49f, and CXCR-4 than their mPB and BM counterparts. CD34+ cells from UCB (and BM) exhibited significantly lower ex vivo transmigration than those from mPB, which were largely blocked by neutralizing antibodies to CD49e or CD49f. Recombinant human tumor necrosis factor-α treatment enhanced ex vivo transmigration of CD34+ cells from UCB and BM by inducing expression of the matrix metalloproteinases MMP-2/MMP-9. Short-term treatment of UCB-derived CD34+ cells with rHu-stem cell factor (rHuSCF) up-regulated levels of the homing-related molecules with their increased ex vivo transmigratory and in vivo homing potential. Conclusion. Our results indicate that disadvantageous transmigratory behavior of HS/PCs from UCB, which might partly explain the delayed reconstitution after UCBT, can be reversed by ex vivo manipulation with rHuSCF.

UR - http://www.scopus.com/inward/record.url?scp=10744232928&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10744232928&partnerID=8YFLogxK

U2 - 10.1016/j.exphem.2003.08.016

DO - 10.1016/j.exphem.2003.08.016

M3 - Article

C2 - 14662330

AN - SCOPUS:10744232928

VL - 31

SP - 1237

EP - 1246

JO - Experimental Hematology

JF - Experimental Hematology

SN - 0301-472X

IS - 12

ER -