Mild heat treatment primes human CD34<sup>+</sup> cord blood cells for migration toward SDF-1α and enhances engraftment in an NSG mouse model

Maegan L. Capitano, Giao Hangoc, Scott Cooper, Hal Broxmeyer

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Simple efforts are needed to enhance cord blood (CB) transplantation. We hypothesized that short-term exposure of CD34<sup>+</sup> CB cells to 39.5C would enhance their response to stromal-derived factor-1 (SDF-1), by increasing lipid raft aggregation and CXCR4 expression, thus leading to enhanced engraftment. Mild hyperthermia (39.5C) significantly increased the percent of CD34<sup>+</sup> CB that migrated toward SDF-1. This was associated with increased expression of CXCR4 on the cells. Mechanistically, mild heating increased the percent of CD34<sup>+</sup> cells with aggregated lipid rafts and enhanced colocalization of CXCR4 within lipid raft domains. Using methyl-β-cyclodextrin (MβCD), an agent that blocks lipid raft aggregation, it was determined that this enhancement in chemotaxis was dependent upon lipid raft aggregation. Colocalization of Rac1, a GTPase crucial for cell migration and adhesion, with CXCR4 to the lipid raft was essential for the effects of heat on chemotaxis, as determined with an inhibitor of Rac1 activation, NSC23766. Application-wise, mild heat treatment significantly increased the percent chimerism as well as homing and engraftment of CD34<sup>+</sup> CB cells in sublethally irradiated non-obese diabetic severe combined immunodeficiency IL-2 receptor gamma chain d (NSG) mice. Mild heating may be a simple and inexpensive means to enhance engraftment following CB transplantation in patients.

Original languageEnglish
Pages (from-to)1975-1984
Number of pages10
JournalStem Cells
Volume33
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Fetal Blood
Cell Movement
Blood Cells
Hot Temperature
Lipids
Chemotaxis
Heating
Therapeutics
Transplantation
Wiskott-Aldrich Syndrome
Severe Combined Immunodeficiency
Chimerism
Interleukin-2 Receptors
GTP Phosphohydrolases
Cyclodextrins
Cell Adhesion
Fever

Keywords

  • Chemotaxis
  • Cord blood transplantation
  • Hematopoietic progenitor cells
  • Hematopoietic stem cells
  • Lipid rafts
  • SDF-1/CXCL12

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Mild heat treatment primes human CD34<sup>+</sup> cord blood cells for migration toward SDF-1α and enhances engraftment in an NSG mouse model. / Capitano, Maegan L.; Hangoc, Giao; Cooper, Scott; Broxmeyer, Hal.

In: Stem Cells, Vol. 33, No. 6, 01.06.2015, p. 1975-1984.

Research output: Contribution to journalArticle

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