Adipose-Derived Stromal Cell Autologous Transplantation Ameliorates Pulmonary Arterial Hypertension Induced by Shunt Flow in Rat Models

Abstract

Hyperkinetic pulmonary arterial hypertension (PAH) severely influences the success of operation for congenital heart disease and deteriorates the prognosis of disease. Adipose-derived stromal cell (ADSC) is a good alternative multipotent stem cell for regeneration medicine. PAH rat models were established by arteriovenous shunt and ADSCs were isolated, cultured, and labeled in vitro. Twelve weeks after shunt operation, rats received an injection of 5 × 10(7) ADSCs. Two weeks after transplantation, hemodynamic abnormality induced by the shunt flow and the hypertrophy of right ventricle were reversed, which was confirmed by invasive measurement and echocardiography examination. The PAH rats receiving cell transplantation demonstrated decreased remodeling of small arteries in the lung; immunohistochemistry analysis showed augmented expression of hepatocyte growth factor (HGF) and increased number of pulmonary small arteries. Western blot and real-time reverse transcriptase-polymerase chain reaction indicated that the protein and mRNA levels of HGF and endothelial nitric oxide synthase increased, respectively, in the lung after cell transplantation. Our results suggested that ADSC transplantation can ameliorate PAH induced by shunt flow by enhancing the expression of HGF and subsequently promoting angiogenesis in the injured lung tissue.

Adipose‐derived stem cells improve erectile function partially through the secretion of IGF‐1, bFGF, and VEGF in aged rats

“…ADSCs were cultured from male Sprague–Dawley (SD) rats as previously described (Liu et al ., ). Briefly, inguinal adipose tissues isolated from rats were minced into small fragments and then were incubated with 0.075% collagenase type I (Sigma‐Aldrich, St. Louis, MO, USA) for 90 min at 37 °C with vigorous shaking for 20 sec at 15‐min interval.…”

“…Approximately 1 × 10 5 cells were incubated with antibodies against rat CD29, CD90, CD31, CD34, CD45, and CD106 (BD Biosciences, San Diego, CA, USA) for 30 min at 4 °C in the dark. To confirm the multipotency of ADSCs, the induction of adipocytes and osteoblasts was performed with adipogenic medium (DMEM containing 10% FBS, 0.5 mmol/L isobutylmethylxanthine, 200 μmol/L indomethacin, 10 μmol/L bovine insulin, and 1 μmol/L dexamethasone) and osteogenic medium (DMEM containing 10% FBS, 10 mmol/L β‐glycerophosphate, 0.1 μmol/L dexamethasone, and 50 μmol/L ascorbic acid), respectively (all the reagents were purchased from Sigma) (Liu et al ., ).…”

Adipose-Derived Stem Cells in Tissue Regeneration: A Review

“…In addition, multiple studies of ischemia describe increased vascularization following ASC administration [145,150,[297][298][299][300][301][302][303]. Hemodynamic abnormalities in pulmonary arterial hypertension may be reversed using ASCs-a finding thought to be attributable to their induction of angiogenesis and increased formation of small, ISRN Stem Cells pulmonary arteries [304]. Increased capillary densities and higher blood flow have been reported in several studies using ASCs for the healing of skin wounds and improvement of skin flap survival [305,306].…”

Vascular Repair and Regeneration as a Therapeutic Target for Pulmonary Arterial Hypertension

“…One frequently investigated cell population is constituted of BM-derived MSCs [23]. Several groups have shown that transplantation of BM-derived MSCs can reduce vascular remodeling and PAH in the monocrotaline (MCT) model [54–56], in a high flow-induced model of PAH [57, 58] and a model of bronchopulmonary dysplasia and associated PH [59]. It is interesting that even intratracheal administration of MSCs results in reduced PAH in the MCT model [60].…”