Bone marrow CD34 cells expanded on human brain endothelial cells reconstitute lethally irradiated baboons in a variable manner

Hiroto Araki, John P. Chute, Benjamin Petro, Lisa Halliday, Ronald Hoffman, Nadim Mahmud

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Increased cell dose has a positive impact on the therapeutic outcome of bone marrow (BM) hematopoietic stem cell (HSC) transplant. However, methods to successfully expand BM HSCs have yet to be achieved. It has been shown previously that ex vivo expansion of BM cells using porcine microvascular endothelial cells can rescue a baboon from a lethal dose of radiation. However, in a prior study, baboons that received CD34 cell doses less than 4×106 cells/kg body weight failed to achieve hematopoietic reconstitution. In our present study we used human brain endothelial cells (HUBECs) and cytokines to expand BM cells, and examined their ability to provide hematopoietic reconstitution in three lethally irradiated baboons following autologous transplant as a surrogate preclinical model. After ex vivo culture, the grafts represented a 1.8- to 2.1-fold expansion of CD34 cells, a 3.7- to 13.2-fold increase of colony-forming cells, and a 1.9- to 3.2-fold increase of cobblestone area-forming cells, in comparison to the input cell numbers. Despite transplanting CD34 cell grafts displaying a comparable degree of expansion, there was an obvious variability in the kinetics of hematopoietic reconstitution. The variation in hematopoietic reconstitution cannot be fully explained by the properties tested in expanded CD34 cells, and warrant caution against taking into account such attributes as cell dose, expression of adhesion molecules, and migration as a measure of successful expansion of HSCs.

Original languageEnglish
Pages (from-to)1121-1127
Number of pages7
JournalLeukemia and Lymphoma
Volume51
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Baboon
  • Ex vivo expansion
  • Hematopoietic stem cells
  • Human brain endothelial cells
  • Microenvironment

Fingerprint

Dive into the research topics of 'Bone marrow CD34 cells expanded on human brain endothelial cells reconstitute lethally irradiated baboons in a variable manner'. Together they form a unique fingerprint.

Cite this