Combining ex vivo gene therapy and vascular network bioengineering: schematic diagram. (A) ECFCs and MSCs are obtained from the patient's own blood and BM, respectively. A gene encoding for hEPO is inserted into culture-expanded ECFCs, and the transfected cells (epoECFCs) are then selected out from the nontransfected ones. Culture-expanded epoECFCs and MSCs are combined in a collagen/fibrin–based gel and prepared for subcutaneous injection into the patient. (B) After injection, the transplanted cells engraft, forming a network of functional blood vessels that are connected to the patient's vasculature. The EPO-producing cells, epoECFCs, line the lumens of these bioengineered vessels. Consequently, EPO is readily secreted into the bloodstream of the patient and distributed systemically.