Enhanced engraftment of EPO-transduced human bone marrow stromal cells transplanted in a 3D matrix in non-conditioned NOD/SCID mice.
Intravenous infusion of bone marrow stromal cells (BMSCs) has been proposed as a means to support hematopoiesis in bone marrow transplantation or as a vehicle for gene therapy. However, it seems that this route of injection leads to engraftment of a small proportion of BMSCs, possibly because they are unable to cross the endothelial barrier. We have transplanted human BMSCs, ex vivo expanded and transduced with a retrovirus encoding the human erythropoietin gene, either intravenously or subcutaneously with or without a tridimensional scaffold in non-conditioned NOD/SCID mice. Efficiency of engraftment was evaluated monitoring the hematocrit levels. Systemic infusion never significantly increased hematocrit levels, whereas subcutaneous transplantation of the same number of cells induced an important increase of the hematocrit (approximately 70%) for at least 2 months. A substantial increase in the length of the response was observed when cells were subcutaneously transplanted in a tridimensional scaffold. To determine whether the transient effect was due to cell loss or to reduction in expression, the cells implanted into a tridimensional scaffold were recovered, expanded in vitro, and re-implanted in a new group of mice. Again the hematocrit levels rose 2 weeks after transplantation ( approximately 70%). These results demonstrate that ex vivo expanded human BMSCs are not quantitatively transplantable by systemic infusion in non-conditioned recipients, whereas the local implantation into a tridimensional scaffold allows long-term engraftment and efficient expression of a foreign gene.
Daga
A
A
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Muraglia
A
A
Quarto
R
R
Cancedda
R
R
Corte
G
G
D017667:Adipocytes; D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D001842:Bone and Bones / Q000166:cytology; D002454:Cell Differentiation; D019902:Chondrocytes; D004921:Erythropoietin / Q000235:genetics*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D051379:Mice; D016513:Mice, SCID; D012190:Retroviridae / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D014161:Transduction, Genetic / Q000379:methods*; D014184:Transplantation, Homologous
D004921:Erythropoietin