Cell-Based Treatment of Ischemic Diseases: Rationale for Transplanting Human Adipose-Derived Progenitor Cells Instead of Freshly Isolated Stromal Cells

Human stromal cells are easily isolated from adipose in the clinic, secrete angiogenic proteins, and differentiate multi-lineage progenitor cells. Since angiogenesis and organogenesis are normally coupled, we hypothesized that human adipose-derived progenitor cells (huAPCs) modulate levels of Vascular Endothelial Growth Factor (VEGF), a key angiogenic protein, in a lineage-dependent manner. Human stromal cells were isolated from lipo-aspirate with a Reviticell kit, seeded in 6-well plates and incubated under normoxic conditions in lineage-specific differentiation media. Immuno-assay of conditioned media at 7 days from nearly (~80%) confluent monolayers confirmed that levels of VEGF (pg/ml) were lineage-dependent: undifferentiated = 73.8, osteogenic = 166.5, chondrogenic = 43.6, adipogenic = 78.7. The 2-fold increase in VEGF by osteogenic progenitors foreshadows bone’s highly vascular structure whereas the 1.7-fold decrease in VEGF by chondrogenic progenitors foreshadows cartilage’s avascular structure (note: 2-fold decrease of VEGF in mouse knock-out mutants is known to be embryonic lethal). Our data suggests that cardiomyogenic differentiation media would also increase VEGF secretion by huAPCs. Conclusion: Differentiation of huAPCs modulates levels of VEGF secretion and, in two extreme cases, foreshadows the extent of blood vessel formation in vivo. Programming angiogenic potential before heterologous cell transplantation could improve the success of therapeutic angiogenesis.