Effects of Transplanted Human Cord Blood-Mononuclear Cells on Pulmonary Hypertension in Immunodeficient Mice and Their Distribution

Abstract

There are many patients who are suffer from pulmonary artery hypertension (PAH) due to pulmonary vascular obstructive disease or limited pulmonary vasculature with or without congenital heart defects. Although there has been significant progress in the development of medication for PAH over the past two decades, most patients with severe PAH have shown little favorable response to any medication and their prognosis has been very poor.Results of recent studies using animal models with hypoxia-or monocrotaline (MCT) -induced pulmonary hypertension (PH) and results of a human pilot study have shown that cellular therapy using endothelial progenitor cells harvested from large quantities of peripheral blood or bone marrow (BM) blood contributed to pulmonary vascular remodeling, thus providing some useful clues for PAH treatment (1 -4). Also, our previous study showed that syngeneic BM mononuclear cells improved MCT-induced PH in mice model (5). However, harvesting these cells from large quantities of peripheral blood or BM blood is very invasive and dangerous for patients with severe PAH, especially for children.In a recent study, it was shown that a single low dose (10 6 cells) of human umbilical cord blood-derived mononuclear cells (hUCBMNCs) administered intravenously to G93A mice with amyotrophic lateral sclerosis delayed symptom progression and modestly prolonged lifespan (6). It has been shown that human umbilical cord blood contains abundant with hematopoietic stem cells, mesenchymal stem cells, and endothelial progenitor cells that are able to differentiate into nerve cells and endothelial cells (7 -10).Therefore, we hypothesized that hUCB-MNC transplantation may provide a new therapeutic potential for patients with severe PAH or limited pulmonary vasculature. The aims of this study were to investigate whether hUCB -MNCs themselves rather than hUCBplasma improve PH in MCT-treated nude mice and to reveal the locations of hUCB-MNCs in the lung. METHODS Animal PreparationBALB/c Slc-nu/nu female immunodeficient mice (Japan SLC, Tokyo, Japan) were used at 8 weeks of age. We anesthetized the mice with ketamine (100 mg/kg) and xylazine (10 mg/kg). Animal care and procedures were in accordance with the institutional guidelines. This study was approved by a university ethics review board (#912), and the animal procedures were conformed to the NIH guidelines (Guide for the care and use of laboratory animals). Pulmonary Hypertension ModelsMice received monocrotaline (MCT) (C16H26NO6 ; Sigma-Aldrich, Lyon, France) treatment. MCT treatment was previously demonstrated to be capable of inducing PH in mice (5, 11).MCT was suspended in 0.1 N HCl, which was adjusted to pH 7.0 with NaOH and diluted in phosphate-buffered saline (PBS). A single injection of MCT (80 mg Abstract : Objectives : To investigate the effects of human umbilical cord blood-derived mononuclear cell (hUCB-MNC) transplantation on pulmonary hypertension (PH) induced by monocrotaline (MCT) in immunodeficient mice and their distribution. Methods : MCT was admin...

Umbilical cord blood stem cells transplantation as an adjunctive treatment strategy for liver cirrhosis in Chinese population: a meta-analysis of effectiveness and safety

“… 4 , 12 However, the procedure of bone marrow aspiration was invasive, and quantity and quality of bone marrow stem cells (BMSCs) are age-dependent, which limit their clinical potentiality. 15 – 18 As an alternative source of BMSCs, umbilical cord blood stem cells (USCs) showed promising clinical application prospects. USCs are composed of immature immune cells and multipotent stem cells such as MSCs, endothelial progenitor cells (EPCs) and HSCs.…”