Transplantation of Human Umbilical Mesenchymal Stem Cells from Wharton's Jelly after Complete Transection of the Rat Spinal Cord

BACKGROUND: Human umbilical mesenchymal stem cells (HUMSCs) isolated from Wharton's jelly of the umbilical cord can be easily obtained and processed compared with embryonic or bone marrow stem cells. These cells may be a valuable source in the repair of spinal cord injury. METHODOLOGY/PRINCIPAL FINDINGS: We examine the effects of HUMSC transplantation after complete spinal cord transection in rats. Approximately 5x10(5) HUMSCs were transplanted into the lesion site. Three groups of rats were implanted with either untreated HUMSCs (referred to as the stem cell group), or HUMSCs treated with neuronal conditioned medium (NCM) for either three days or six days (referred to as NCM-3 and NCM-6 days, respectively). The control group received no HUMSCs in the transected spinal cord. Three weeks after transplantation, significant improvements in locomotion were observed in all the three groups receiving HUMSCs (stem cell, NCM-3 and NCM-6 days groups). This recovery was accompanied by increased numbers of regenerated axons in the corticospinal tract and neurofilament-positive fibers around the lesion site. There were fewer microglia and reactive astrocytes in both the rostral and caudal stumps of the spinal cord in the stem cell group than in the control group. Transplanted HUMSCs survived for 16 weeks and produced large amounts of human neutrophil-activating protein-2, neurotrophin-3, basic fibroblast growth factor, glucocorticoid induced tumor necrosis factor receptor, and vascular endothelial growth factor receptor 3 in the host spinal cord, which may help spinal cord repair. CONCLUSIONS/SIGNIFICANCE: Transplantation of HUMSCs is beneficial to wound healing after spinal cord injury in rats

Developments of electric cars and fuel cell hydrogen electric cars

The world continues to strive in the search for clean power sources to run the millions of different vehicles on the road on daily basis as they are the main contributors to toxic emissions releases from internal combustion engines to the atmosphere. These toxic emissions contribute to climate change and air pollution and impact negatively on people's health. Fuel cell devices are gradually replacing the internal combustion engines in the transport industry. Some notable challenges of the PEMFC technology are discussed in this paper. High costs, low durability and hydrogen storage problems are some of the major obstacles being examined in this investigation. The paper explores the latest advances in electric cars technology and their design specifications. The study also compares the characteristics and the technologies of the three types of electric cars now available in the market.interna

Islet-like clusters derived from mesenchymal stem cells in Wharton's Jelly of the human umbilical cord for transplantation to control type 1 diabetes.

BACKGROUND: There is a widespread interest in developing renewable sources of islet-replacement tissue for type I diabetes mellitus. Human mesenchymal cells isolated from the Wharton's jelly of the umbilical cord (HUMSCs), which can be easily obtained and processed compared with embryonic and bone marrow stem cells, possess stem cell properties. HUMSCs may be a valuable source for the generation of islets. METHODOLOGY AND PRINCIPAL FINDINGS: HUMSCs were induced to transform into islet-like cell clusters in vitro through stepwise culturing in neuron-conditioned medium. To assess the functional stability of the islet-like cell clusters in vivo, these cell clusters were transplanted into the liver of streptozotocin-induced diabetic rats via laparotomy. Glucose tolerance was measured on week 12 after transplantation accompanied with immunohistochemistry and electron microscopy analysis. These islet-like cell clusters were shown to contain human C-peptide and release human insulin in response to physiological glucose levels. Real-time RT-PCR detected the expressions of insulin and other pancreatic beta-cell-related genes (Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2) in these islet-like cell clusters. The hyperglycemia and glucose intolerance in streptozotocin-induced diabetic rats was significantly alleviated after xenotransplantation of islet-like cell clusters, without the use of immunosuppressants. In addition to the existence of islet-like cell clusters in the liver, some special fused liver cells were also found, which characterized by human insulin and nuclei-positive staining and possessing secretory granules. CONCLUSIONS AND SIGNIFICANCE: In this study, we successfully differentiate HUMSCs into mature islet-like cell clusters, and these islet-like cell clusters possess insulin-producing ability in vitro and in vivo. HUMSCs in Wharton's Jelly of the umbilical cord seem to be the preferential source of stem cells to convert into insulin-producing cells, because of the large potential donor pool, its rapid availability, no risk of discomfort for the donor, and low risk of rejection

Comparative Effects of Bone Marrow Mesenchymal Stem Cells on Lipopolysaccharide-Induced Microglial Activation

After injury to the CNS, microglia are rapidly activated and concentrated and trigger inflammatory reaction at the sites of injury. Bone marrow mesenchymal stem cells (BMMSC) represent attractive cell sources for treating CNS injury. Although anti-inflammatory and paracrine effects of grafted BMMSC have been shown, direct modulation of BMMSC on microglia in situ remains unclear. The present work employs in vitro transwell assay to characterize the effects of BMMSC on LPS-stimulated microglia. BMMSC are cultivated in serum and serum-free (sf) conditions, namely, BMMSC and BMMSC-sf. Both cultures express major surface markers specific for mesenchymal stem cells. However, the BMMSC-sf exhibit sphere-like structure with reduced expression of two adherent cell markers, CD29 and CD90. Compared to BMMSC-sf, BMMSC are fibroblast like and have faster differentiation potential into neural-like cells. Furthermore, BMMSC release significant levels of TIMP-1 and VEGF, regardless of being alone or in coculture. The downregulated MMP-9 mRNA may be caused by TIMP-1 secretion from BMMSC. Our cell culture system provides a powerful tool for investigating the molecular and cellular changes in microglia-BMMSC cocultures

Human Umbilical Mesenchymal Stem Cell Xenografts Repair UV-Induced Photokeratitis in a Rat Model

Most patients with a corneal injury are administered anti-inflammatory medications and antibiotics, but no other treatments are currently available. Thus, the corneal injury healing is unsatisfactory, affects the vision, and has a risk of blindness in severe cases. Human umbilical mesenchymal stem cells exhibit pluripotent and anti-inflammatory properties and do not cause immunological rejection in the host. Rats were irradiated with type B ultraviolet (UVB) light to generate a stable animal model of photokeratitis. After irradiation-induced photokeratitis, human umbilical mesenchymal stem cells were implanted into the subconjunctival space of the lateral sclera, and the changes in the corneal pathology were evaluated. Three weeks after implantation, many mesenchymal stem cells were visible in the subconjunctival space. These mesenchymal stem cells effectively reduced the extent of injury to the adjacent corneal tissue. They accelerated the epithelial layer repair, reduced the inflammatory response and neovascularization, and improved the disorganization of collagen and fibronectin in the corneal stroma caused by the injury. In conclusion, xenografted human umbilical mesenchymal stem cells can survive in rat eye tissues for a long time, effectively support the structural integrity of injured corneal tissues, restore corneal permeability, and reduce abnormal neovascularization. This study provides a new approach to the treatment of photokeratitis

Reversal of Pulmonary Fibrosis: Human Umbilical Mesenchymal Stem Cells from Wharton’s Jelly versus Human-Adipose-Derived Mesenchymal Stem Cells

Pulmonary fibrosis (PF) is a progressive, non-reversible illness with various etiologies. Currently, effective treatments for fibrotic lungs are still lacking. Here, we compared the effectiveness of transplantation of human mesenchymal stem cells from umbilical cord Wharton’s jelly (HUMSCs) versus those from adipose tissue (ADMSCs) in reversing pulmonary fibrosis in rats. Bleomycin 5 mg was intratracheally injected to establish a severe, stable, single left lung animal model with PF. On Day 21 post-BLM administration, one single transplantation of 2.5 × 107 HUMSCs or ADMSCs was performed. Lung function examination of Injury and Injury+ADMSCs rats displayed significantly decreased blood oxygen saturation and increased respiratory rates, while Injury+HUMSCs rats showed statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Reduced cell number in the bronchoalveolar lavage and lower myofibroblast activation appeared in the rats transplanted with either ADMSCs or HUMSCS than that in the Injury group. However, ADMSC transplantation stimulated more adipogenesis. Furthermore, matrix-metallopeptidase-9 over-expression for collagen degradation, and the elevation of Toll-like receptor-4 expression for alveolar regeneration were observed only in the Injury+HUMSCs. In comparison with the transplantation of ADMSCs, transplantation of HUMSCs exhibited a much more effective therapeutic effect on PF, with significantly better results in alveolar volume and lung function

Changes of blood glucose and serum human insulin levels in STZ-diabetic rats after clusters transplantation.

<p>Blood glucose (A) and serum human insulin (B) detection 1-week after sham or stage 4 islet-like cell cluster transplantation in STZ-induced diabetic rats. Random-fed blood glucose levels were measured in all groups. In C, time-course changes of serum human insulin levels after transplantation. All data are presented as means±SEM (n = 6 in each group). * P<0.05 as compared with before STZ. ^# P<0.05 as compared with after STZ.</p

Detections of nestin, glucagons, insulin, and pancreatic β-cell-related genes in stage-specific cell cluster.

<p>In A, immunocytochemical detection of nestin, glucagon and insulin in stage 2 and stage 4 of differentiated human umbilical cord mesenchymal stem cells. Immunofluorescent images were obtained by confocal microscopy and are representative of at least 6 samples for each antibody. In g and h, DAB was a substrate for the immunostaining of insulin. Results shown are representative of three independent experiments. Original magnification: ×40. In B-a, real-time RT-PCR detected the mRNA expressions of insulin and other pancreatic β-cell-related genes, such as <i>Pdx-1</i>, <i>Hlxb9</i>, <i>Nkx2.2</i>, <i>Nkx6.1</i>, and <i>Glut-2</i> in these islet-like cell clusters. In B-b, real-time RT-PCR detected the insulin mRNA expressions in stage 4 cell clusters comparing to human islets or rat β-cell line RIN-m5F. Data are presented as means±SEM from three independent experiments.</p

Outline of differentiation protocol and stage-specific cell cluster morphology.

<p>Essential factor manipulations at each stage were also shown. Original magnification: ×40.</p