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The aim of this article was to investigate the effects of early and delayed transplantation of adipose tissue-derived mesenchymal stem cells (ADMSCs) on pulmonary vasomotion in monocrotaline (MCT)-induced pulmonary arterial hypertensive (PAH) rats. Adipose tissue-derived mesenchymal stem cells were isolated from inguinal subcutaneous adipose tissue of Sprague-Dawley (SD) rats. Eighty male SD rats were divided into four groups ( n = 20 per group): normal control (Ctr), PAH, early (at day 7, ADMSCs-7), and delayed (at day 14, ADMSCs-14) ADMSC intervention. PAH was induced by a single dose intraperitoneal injection of 40 mg/kg MCT. About 1 × 106 ADMSCs were delivered via left external jugular vein. Mean pulmonary arterial pressure (MPAP) was measured by catheterization at days 21 and 28 after MCT injection. Pulmonary arteriolar endothelium-dependent relaxation (EDdR), endothelium-independent relaxation (EDiR), and vasoconstriction function were evaluated by the physiological vascular ring tension recording system. Mean pulmonary arterial pressure (mmHg) was increased on days 21 (26.88 ± 0.86 vs. 14.88 ± 0.98, P u003c 0.05) and 28 (32.22 ± 0.71 vs. 15.16 ± 0.95, P u003c 0.05) after MCT administration; EDdR and EDiR were lower in PAH rats at the 21st day (pD2:EDdR: 4.85 ± 0.29 vs. 8.12 ± 0.48 and EDiR: 6.28 ± 0.38 vs. 8.64 ± 0.35; all P u003c 0.05) and 28th day (pD2:EDdR: 3.22 ± 0.61 vs. 7.93 ± 0.5 and pD2:EDiR: 5.4 ± 0.55 vs. 8.58 ± 0.41; all P u003c 0.05). Mean pulmonary arterial pressure in ADMSCs-7 was decreased on the 21st day (16.37 ± 0.94 vs. 26.88 ± 0.86 mmHg, P u003c 0.05) and 28th day (18.26 ± 1.41 vs. 32.22 ± 0.71 mmHg, P u003c 0.05). Similarly, MPAP in ADMSC-14 was also lowered on days 21 and 28. EDdR in ADMSCs-7 was increased on day 21 (pD2: 7.48 ± 0.31 vs. 4.85 ± 0.29, P u003c 0.05) and day 28 (6.29 ± 0.52 vs. 3.22 ± 0.61, P u003c 0.05). EDdR in ADMSCs-14 was also increased on day 21 (pD2: 8.08 ± 0.37 vs. 4.85 ± 0.29, P u003c 0.05) and day 28 (6.21 ± 0.67 vs. 3.22 ± 0.61, P u003c 0.05). EDiR in both ADMSCs-7 and ADMSCs-14 was increased on days 21 and 28. There was no significant difference in EDdR and EDiR between ADMSCs-EI and ADMSCs-DI. The impairment of EDdR and EdiR in PA was ameliorated, and PAH was reduced by both early and delayed transplantation of ADMSCs.

european heart journal supplements

Comparison of early and delayed transplantation of adipose tissue-derived mesenchymal stem cells on pulmonary arterial function in monocrotaline-induced pulmonary arterial hypertensive rats