First Report of Histological Evaluation of Human Tissue-Engineered Vasculature

From September 2001 to December 2004, 25 patients underwent a Fontan procedure using tissue-engineered vasculature (TEV) under informed consent and institutional review board approval. Six of these 25 patients died, although no graft-related mortality occurred. The case presented herein is the first case in which the family agreed to the performance of an autopsy to elucidate the late-term histological characteristics of human TEV.

A 16-year-old girl had a history of heart murmur and cyanosis at birth, followed by diagnoses of heterotaxy syndrome (polysplenia), a single right ventricle, pulmonary stenosis, bilateral superior vena cava, a hemiazygos connection, and a common atrium with mild to moderate regurgitation from a common atrioventricular valve. She underwent a Fontan procedure with common atrioventricular valve plasty following staged operations at the age of 4 years. A 12-mm-diameter biodegradable scaffold seeded with mononuclear bone marrow cells was interposed between the hepatic vein and pulmonary artery to accomplish the Fontan procedure. At the age of 16 years, she died of multiple organ failure, low cardiac output syndrome, disseminated intravascular coagulation, pancytopenia, and brain abscessation. An autopsy of the patient was performed, and the tissue samples were evaluated either macroscopically or microscopically for histological analyses. Macroscopic examination showed well-formed tissueengineered vessels connected to the pulmonary artery.

The tissue samples were then fixed in 10% formaldehyde, embedded in paraffin, and sectioned at 4 to 5 μm. Some sections were subjected to hematoxylin and eosin, Masson’s trichrome, Victoria blue–van Gieson, or modified von Kossa staining, which showed components of the four basic vascular layers (endothelial cells, vascular smooth muscle cells, elastic fibers, and collagen fibers) 12 years after implantation of the TEV. Calcified lesions (black-spots lesions) were not observed in any samples. Immunostaining of the remaining sections was performed as previously described using antibodies to factor VIII, alpha smooth muscle actin, myosin heavy chain, smooth muscle myosin heavy chain 1, smooth muscle myosin heavy chain 2, and calponin. Endothelialization and mature vascular smooth muscle cell proliferation  were observed in the human TEV.

Safety of Mesenchymal Stem Cells Therapy in Patients with Inflammatory Bowel Diseases 5 Year Follow-Up

Mesenchymal stromal cells (mesenchymal stem cells; MSC) are a heterogeneous group of cells, that can be isolated from many tissues (bone marrow, adipose tissue, dental pulpe). First described in 1960-years of XX century, MSC have recently received attention in a number of different clinical fields for their potential therapeutic effects.

Although often described as «adult stem cells», MSC’s have limited cellular differentiation ability. Instead, pre-clinical evidence suggests that MSCs exert their beneficial effects largely through immunomodulatory and paracrine mechanisms. MSCs home to sites of inflammation and secrete bioactive molecules, and thus may be especially effective in different pro-inflammatory diseases.

There is a growing body of literature demonstrating the efficacy of MSC therapy in a variety ofpre-clinical models, including acute lung injury, septic shock, acutemyocardial infarction. Several small clinical trials have investigated efficacy and safety of MSCs in diseases including chronic heart failure, acute myocardial infarction, hematological malignancies, Crohn disease and graft-versus-host disease.