Human mesenchymal stem cells (hMSCs) are excellent candidates for ex vivo gene transfer and cell therapy in various systems. However, hMSCs are mortal somatic cells, and thus invariably enter an irreversible growth arrest after a finite number of cell divisions in culture. It has been proposed that this is due to telomere shortening. In this study, pGRN145 plasmid containing human telomerase reverse transcriptase (hTRT) was introduced into fetal dermis-derived hMSCs. Single-cell clones positive for telomerase activity and hTRT mRNA were selected and expanded. Single-cell-derived hTRT(+) cells could be expanded rapidly in vitro and passaged up to 70 doublings without showing senescence. FACScan flow cytometer showed that hTRT(+) cells were positive for CD29, CD44, CD105, and CD166, while CD31, CD45, CD34, vWF, and HLA-DR were negative. Under suitable conditions, hTRT(+) cells have the ability of multiple lineage differentiation, including bone, fat, and nerve. Furthermore, transplantation of hTRT(+) cells could protect NOD/SCID mice from lethal irradiation. Thus, these cells may be an ideal cell source for promoting hematopoietic recovery after radiotherapy.
Bone Marrow Transplantation (2005) 36, 355-365.