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

Published

Journal Article

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 x 10(6) 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.

Full Text

Cited Authors

  • Araki, H; Chute, JP; Petro, B; Halliday, L; Hoffman, R; Mahmud, N

Published Date

  • June 2010

Published In

Volume / Issue

  • 51 / 6

Start / End Page

  • 1121 - 1127

PubMed ID

  • 20470216

Pubmed Central ID

  • 20470216

Electronic International Standard Serial Number (EISSN)

  • 1029-2403

International Standard Serial Number (ISSN)

  • 1042-8194

Digital Object Identifier (DOI)

  • 10.3109/10428191003786774

Language

  • eng