Human mesenchymal stem cells (hMSCs) expressing truncated soluble vascular endothelial growth factor receptor (tsFlk‐1) following lentiviral‐mediated gene transfer inhibit growth of Burkitt's lymphoma in a murine model

Abstract

Human MSC are easily transduced by pseudotyped lentiviral particles but there is inter-donor variation in transduction efficiency. Gene-modified MSC expressing a gene of therapeutic potential can moderate growth of haematological malignancies.

A new xenograft model of myeloma bone disease demonstrating the efficacy of human mesenchymal stem cells expressing osteoprotegerin by lentiviral gene transfer

“…MSC GPO expressed low levels of hOPG in culture at similar levels to untransduced MSC (data not shown). MSC transduced with lentiviral constructs retain their differentiating capacity and phenotype as reported previously, 26 with no significant differences seen between MSC OPG , MSC GPO and untransduced MSC (data not shown).…”

“…Human bone marrow-derived MSCs were isolated by standard means and characterized by the ability to differentiate into osteoblasts and adipocytes, and the retention of a stable immunophenotype (SH2 þ , SH4 þ , CD13 þ , CD49e þ , CD34À, CD45À) for up to 14 passages. Using conditions we have previously optimized, 26 early passage 2-4 hMSCs were transduced with a bicistronic lentiviral construct containing cDNA encoding OPG and eGFP (MSC OPG , Figure 4a). Control MSCs were derived from the same bone marrow donor, and transduced with a bicistronic lentiviral construct with the cDNA for OPG cloned in reverse (MSC GPO , Figure 4a).…”

Factors that influence short-term homing of human bone marrow-derived mesenchymal stem cells in a xenogeneic animal model

“…Human MSC were cultured from the adherent fraction of bone marrow mononuclear cells, and characterized for phenotype and differentiation function according to established protocols, 39,2 (see the Online Supplementary Methods).…”

“…2,3 Human MSC may prove useful for enhancing hematopoietic stem cell transplantation, 4 modulating graft-versus-host disease, 5 treating disorders of bone, cartilage 6 and muscle 7 and delivering therapeutic genes. 8 The successful employment of human MSC for these in vivo strategies relies upon the efficient localization and retention of cells within appropriate tissues.…”

The isolation and characterization of putative mesenchymal stem cells from the spiny mouse

“…They also exhibited characteristic morphological features of MSCs, such as plastic adherence and spindle-shaped fibroblastic morphology (Eslaminejad et al 2006;Izadpanah et al 2005;Lange et al 2005;Tang et al 2006). MSCs differentiate by default in vivo into cell lineages of mesenchymal tissues, including bone, cartilage, fat, muscle, and myelosupportive stroma (Kyriakou et al 2006). Similarly, isolated MSCs can be directed to differentiate in vitro, by culture with lineage specific differentiation medium, to differentiate down the osteogenic, adipogenic and chondrogenic lineages (Gregory et al 2005).…”