Progenitor Enrichment and Increased Residence Time Enhance Arteriogenic Response to Bone Marrow‐Derived Cells

Bone marrow has been used to treat ischemic disease by stimulating growth of capillaries and maturation of arterioles. It remains unclear whether the delivery of a purified progenitor population would elicit greater benefit compared to the delivery of a more heterogeneous cellular population, such as whole bone marrow (WBM). The microvascular impact of WBM and a Lin − Sca‐1 + progenitor subpopulation was observed in a mouse skinfold chamber. Progenitors were isolated from WBM and injected surrounding the chamber. Controls received injections of WBM or saline. Cells were quickly cleared from the tissue, but by day 10 arteriole diameter growth was 35% higher in progenitor recipients. Next, the delivery method was altered to increase tissue residence time of WBM cells, to determine whether prolonged application of a more heterogeneous population could elicit a similar response. An alginate bead of WBM was placed in the chamber. By day 10, arteriole diameters had enlarged 63% more compared to controls. Encapsulation allowed WBM to elicit an arteriogenic impact that is comparable to that of the injected progenitor recipients. These results indicate that temporary exposure to a progenitor subpopulation within WBM can have a significant impact on microvascular remodeling, while a more heterogeneous cell population requires prolonged tissue exposure to produce a comparable arteriogenic response. Support by NIH HL65958