Female MSC have more marked effects on pulmonary hypertension.

<p>(a) Female MSC improve right ventricular systolic pressure (RVSP) to a greater degree than male MSC. The efficacy of MSC in improving RVSP in female (b) and male (c) animals is not dependent on the sex of the recipient. (*<i>P</i> < 0.05: RA vs hyperoxia-PL; † <i>P</i> <0.05: hyperoxia-PL vs hyperoxia male or female MSC; $ <i>P</i> <0.05: hyperoxia male MSC vs hyperoxia female MSC). White bars are RA and black bars are hyperoxia.</p

Female MSC exhibit greater anti-remodeling effects.

<p>(a) Lung sections stained with Von Willebrand Factor (green), α-smooth muscle actin (red), and DAPI (blue), demonstrating improved vascular remodeling in hyperoxia-exposed pups treated with male or female MSC. Original magnification X400. (b) Female MSC are superior to male MSC in reducing the percentage of fully muscularized blood vessels. (c) IT male or female MSC improved medial wall thickness of vessels (20–50 μm). In female pups, IT male or female MSC similarly improve the percentage of muscularized vessels (d), and the medial wall thickness (e). In male pups, IT female MSC are superior to male MSC in improving the percentage of muscularized blood vessels (f), while being as effective in reducing the medial wall thickness (g). (*<i>P</i> < 0.05: RA vs hyperoxia-PL; † hyperoxia-PL vs hyperoxia male or female MSC; $ <i>P</i> <0.05: hyperoxia male MSC vs hyperoxia female MSC). White bars are RA and black bars are hyperoxia unless otherwise specified.</p

Intra-tracheal (IT) administration of male or female MSC similarly improves alveolarization.

<p>(a) Hematoxylin and eosin stained lung sections demonstrating improved alveolar structure in hyperoxia-exposed pups treated with IT male or female MSC. Original magnification X 200. Bars = 100 μm. IT male or female MSC similarly increased mean linear intercept (b) and decreased radial alveolar count (c). IT male or female MSC similarly improve RAC in female (d) and male (e) animals. (*<i>P</i> < 0.05; Room air (RA) vs hyperoxia- placebo (PL), † <i>P</i> <0.05; hyperoxia -PL vs hyperoxia male or female MSC). White bars are RA and black bars are hyperoxia.</p

Female MSC produce more VEGF and IL-10 after 24 hours in culture.

<p>(a) VEGF concentration as measured by ELISA in male and female MSC (b) IL-10 concentration as measured by ELISA in male and female MSC (* <i>P</i> < 0.05; Male vs Female MSC, N = 3 experiments/group).</p

IT male or female MSC similarly improve lung angiogenesis.

<p>(a) Lung sections stained with Von Willebrand Factor (green) and 4’6-diamidino-2-phenylindole (DAPI: blue), demonstrating improved vascular density in hyperoxia-exposed pups treated with male and female MSC at P7. Original magnification X 100. Bars = 100 μm. (b) IT male and female MSC similarly increased lung vascular density in hyperoxic pups. (c) Female MSC normalizes lung VEGF concentration in hyperoxia. Female and male MSC exhibit similar efficacy in improving lung angiogenesis in female (d) and male (e) animals. (*<i>P</i> < 0.05: RA vs hyperoxia-PL; † <i>P</i> <0.05: hyperoxia-PL vs hyperoxia male or female MSC; $ <i>P</i> <0.05: hyperoxia male MSC vs hyperoxia female MSC). White bars are RA and black bars are hyperoxia.</p