Adhesion to fibronectin maintains regenerative capacity during ex vivo culture and transduction of human hematopoietic stem and progenitor cells

Recent reports have indicated that there is poor engraftment from hematopoi etic stem cells (HSC) that have traversed cell cycle ex vivo, However, indu cing cells to cycle in culture is critical to the fields of ex vivo stem ce ll expansion and retroviral-mediated gene therapy. Through the use of a xen ograft model, the current data shows that human hematopoietic stem and prog enitor cells can traverse M phase ex vivo, integrate retroviral vectors, en graft, and sustain longterm hematopoiesis only if they have had the opportu nity to engage their integrin receptors to fibronectin during the culture p eriod. If cultured in suspension under the same conditions, transduction is undetectable and the long-term multilineage regenerative capacity of the p rimitive cells is severely diminished. (C) 1998 by The American Society of Hematology.