Is the intravascular administration of mesenchymal stem cells safe? Mesenchymal stem cells and intravital microscopy.
ABSTRACT We investigated the kinetics of human mesenchymal stem cells (MSCs) after intravascular administration into SCID mouse cremaster vasculature by intravital microscopy. MSCs were injected into abdominal aorta through left femoral artery at two different concentrations (1 x 10(6) or 0.2 x 10(6) cell). Arterial blood velocity decrease by 60 and 18% 1 min after high/low dose MSCs injection respectively. The blood microcirculation was interrupted after 174+/-71 and 485+/-81 s. Intravital microscopy observation and histopathologic analysis of cremaster muscles indicated MSCs were entrapped in capillaries in both groups. 40 and 25% animals died of pulmonary embolism respectively in both high and low MSCs dose groups, which was detected by histopathologic analysis of the lungs. Intraarterial MSCs administration may lead to occlusion in the distal vasculature due to their relatively large cell size. Pulmonary sequestration may cause death in small laboratory animals. MSCs should be used cautiously for intravascular transplantation.
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ABSTRACT: Bioreactors have been widely acknowledged as valuable tools to provide a growth environment for engineering tissues and to investigate the effect of physical forces on cells and cell-scaffold constructs. However, evaluation of the bioreactor environment during culture is critical to defining outcomes. In this study, the performance of a hydrostatic force bioreactor was examined by experimental measurements of changes in dissolved oxygen (O2), carbon dioxide (CO2), and pH after mechanical stimulation and the determination of physical forces (pressure and stress) in the bioreactor through mathematical modeling and numerical simulation. To determine the effect of hydrostatic pressure on bone formation, chick femur skeletal cell-seeded hydrogels were subjected to cyclic hydrostatic pressure at 0-270 kPa and 1 Hz for 1 h daily (5 days per week) over a period of 14 days. At the start of mechanical stimulation, dissolved O2 and CO2 in the medium increased and the pH of the medium decreased, but remained within human physiological ranges. Changes in physiological parameters (O2, CO2, and pH) were reversible when medium samples were placed in a standard cell culture incubator. In addition, computational modeling showed that the distribution and magnitude of physical forces depends on the shape and position of the cell-hydrogel constructs in the tissue culture format. Finally, hydrostatic pressure was seen to enhance mineralization of chick femur skeletal cell-seeded hydrogels.Tissue Engineering Part C Methods 06/2014; · 4.64 Impact Factor
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ABSTRACT: Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. The only interventions that have proven beneficial are protective ventilation strategies and fluid conservation approaches. New therapies are needed to address this common clinical problem. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS. In the present study endotoxin was infused intravenously into 14 sheep from which 6 received different doses of adult stem cells by intrabronchial delivery to evaluate the effect of stem cell therapy. After administration of endotoxin, there was a rapid decline in oxygenation to hypoxemic values, indicative of severe-to-moderate ARDS. None of the animals treated with saline solution recovered to normal baseline values during the 6 hours that the animals were followed. In contrast, sheep treated with a dose of 40 million adult stem cells returned their levels of oxygen in their blood to baseline two hours after the cells were infused. Similarly, improvements in carbon dioxide (CO2) clearance, pulmonary vascular pressures and inflammation were observed and confirmed by histology and by the decrease in lung edema. We concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS.Stem Cell Research & Therapy 03/2014; 5(2):42. · 3.65 Impact Factor
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ABSTRACT: Hyposalivation is an intractable side‑effect of radiotherapy for head and neck cancer. It is caused by the irreversible loss of acinar cells and decreased saliva secretion. However, this situation severely compromises the quality of life of affected patients. Currently, there is no effective treatment for this condition. In the present study, we developed a novel approach to regenerate the function of the irradiation‑damaged salivary glands using human adipose tissue‑derived stem cell (hADSC) intraglandular transplantation. ZsGreen‑labeled hADSCs were adoptively transferred into Sprague‑Dawley (SD) rat submandibular glands immediately following exposure to 18 Gy irradiation. A higher salivary flow rate (SFR) was observed in the hADSC‑treated group. Tissue improvement, including angiogenesis, anti‑apoptosis and anti‑fibrosis, was detected in the hADSC‑treated glands as compared to the untreated glands. Quantitative reverse transcription PCR (RT-qPCR) revealed a significantly higher expression of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), cyclooxygenase‑2 (COX‑2) and matrix metalloproteinase‑2 (MMP‑2) in the hADSC‑treated rats. Furthermore, immunohistochemical analysis indicated that the hADSCs had differentiated into acinar and ductal cells in the rat submandibular glands. Thus, our results suggest that hADSCs are able to regenerate irradiation‑damaged salivary glands through glandular transplantation.International Journal of Molecular Medicine 07/2014; · 1.96 Impact Factor