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

Abstract

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 < 0.05) and 28 (32.22 ± 0.71 vs. 15.16 ± 0.95, P < 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 < 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 < 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 < 0.05) and 28th day (18.26 ± 1.41 vs. 32.22 ± 0.71 mmHg, P < 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 < 0.05) and day 28 (6.29 ± 0.52 vs. 3.22 ± 0.61, P < 0.05). EDdR in ADMSCs-14 was also increased on day 21 (pD2: 8.08 ± 0.37 vs. 4.85 ± 0.29, P < 0.05) and day 28 (6.21 ± 0.67 vs. 3.22 ± 0.61, P < 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.