EPC infusions accelerate the recovery of BM sinusoidal vessels, BM cellularity, HSC regeneration, and mature blood counts. (A) EPC infusion for 5 days accelerates recovery of BM cellularity following total body irradiation. BM cross-sections (× 400) are shown from a normal BALB/c mouse and from BALB/c mice following 550 cGy TBI and treatment with PBS or EPCs for 5 days (“Methods”). BM hypocellularity and BM vasculature disruption were more pronounced in the PBS treatment group at all time points. Recovery of megakaryocytes (yellow arrows) occurred earlier in mice that received EPCs (day 15) compared with controls. (B) EPC infusions accelerate the recovery of BM sinusoidal vessels following TBI. Expression of MECA-32 was examined in BM sections from normal and irradiated BALB/c mice. BM from a normal mouse demonstrated narrow sinusoidal vessels (brown). Overt disruption of BM vasculature was evident in irradiated, PBS-treated mice at days 10 and 15 as compared with normal mice. Preservation of sinusoidal vessels (day 10) and assembly of nascent vessels (day 15; red arrows) was evident earlier in the EPC-treated mice compared with PBS-treated mice (day 20). The BM vasculature in EPC-treated mice approached normal appearance by day 20. (C) EPC infusions augment the recovery of phenotypic BM hematopoietic progenitor cells in irradiated mice. EPC-treated mice (■) demonstrated significantly increased percentages of BM c-kit⁺lin⁻ progenitors (top left) at days 10, 15, and 20 following 550 cGy irradiation (P = .004, P = .004, and P = .04, respectively) and BM KSL cells at days 10 and 15 after irradiation (right; P = .02 and P = .04) compared with controls (▩). The numbers of BM CFCs were also significantly increased at days 10 and 15 in EPC-treated mice compared with controls (bottom; P = .001 and P = .003). Data represent the mean plus SD of n = 6 experiments. *P < .05 for difference between EPC-treated mice and controls. (D) The scatterplot shows the percentage of CD45.1⁺ donor cell engraftment in the PB of CD45.2⁺ mice that received transplants of limiting doses of CD45.1⁺ BM cells collected at day 20 from mice irradiated with 700 cGy TBI followed by PBS treatments (control) or mice irradiated identically and then infused with EPCs. Mice that received transplants of BM cells from EPC-treated donors (□) demonstrated significantly higher donor CD45.1⁺ cell repopulation at 12 weeks after transplantation than mice that received transplants of BM from PBS-treated mice (■). Each dot represents a mouse that underwent transplantation (n = 76 mice). Donor BM cell doses transplanted per mouse are shown at the bottom of the figure. All mice received transplants of 10⁵ host BM cells for competition. Lines represent the mean levels of CD45.1⁺ cell engraftment in each group. (Ei) EPC-treated mice (blue line) demonstrated earlier recovery of WBCs compared with controls (black line). *P = .006 and P = .04 for difference in WBCs between EPC-treated mice and controls at days 16 and 18. (Eii) EPC-treated mice also demonstrated increased neutrophil counts compared with controls. *P = .04, P = .04, P < .001, P < .001, and P = .002 for differences between EPC-treated mice and controls at days 9, 11, 16, 18, and 21. (Eiii) Platelet recovery was also significantly accelerated in EPC-treated mice compared with controls. *P = .007, P = .006, P = .002, and P = .03 for differences between EPC-treated mice and controls at days 11, 14, 16, and 18. Data represent the means plus SEM of n = 10 to 12 mice PB samples per time point.