Title: Development of a tissue-engineered vascular graft combining a biodegradable scaffold, muscle-derived stem cells and a rotational vacuum seeding technique.
Publication of the Month 2007
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Prospective Identification of Myogenic Endothelial Cells in Human Skeletal Muscle
Summary: This manuscript documents anatomic, molecular and developmental relationships between endothelial and myogenic cells within human skeletal muscle. Cells coexpressing myogenic and endothelial cell markers (CD56, CD34, CD144) were identified by immunohistochemistry and flow cytometry. These myoendothelial cells regenerate myofibers in the injured skeletal muscle of severe combined immunodeficiency mice more effectively than CD56+ myogenic progenitors. They proliferate long term, retain a normal karyotype, are not tumorigenic and survive better under oxidative stress than CD56+ myogenic cells. Clonally derived myoendothelial cells differentiate into myogenic, osteogenic and chondrogenic cells in culture. Myoendothelial cells are amenable to biotechnological handling, including purification by flow cytometry and long-term expansion in vitro, and may have potential for the treatment of human muscle disease.
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Agent-based model of inflammation and wound healing: insights into diabetic foot ulcer pathology and the role of transforming growth factor-b1
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Prospective identification of myogenic endothelial cells in human skeletal muscle.
Summary: Myoendothelial cells taken from the blood vessels are much more efficient at forming muscle than other sources of stem cells known as satellite and endothelial cells. A thousand myoendothelial cells transplanted into the injured skeletal muscle of immunodeficient mice produced, on average, 89 muscle fibers, compared with nine and five muscle fibers for endothelial and satellite cells, respectively. Myoendothelial cells also showed no propensity to form tumors, a concern with other stem cell therapies.
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: Comparisons to a 4 h (51)Cr-release assay.
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Stem and progenitor cells in skeletal muscle development, maintenance, and therapy
Summary: Satellite cells are dormant progenitors located at the periphery of skeletal myofibers that can be triggered to proliferate for both self-renewal and differentiation into myogenic cells. In addition to anatomic location, satellite cells are typified by markers such as M-cadherin, Pax7, Myf5, and neural cell adhesion molecule-1. The Pax3 and Pax7 transcription factors play essential roles in the early specification, migration, and myogenic differentiation of satellite cells. In addition to muscle-committed satellite cells, multi-lineage stem cells encountered in embryonic, as well as adult, tissues exhibit myogenic potential in experimental conditions. These multi-lineage stem cells include side-population cells, muscle-derived stem cells (MDSCs), and mesoangioblasts. Although the ontogenic derivation, identity, and localization of these non-conventional myogenic cells remain elusive, recent results suggest their ultimate origin in blood vessel walls. Indeed, purified pericytes and endothelium-related cells demonstrate high myogenic potential in culture and in vivo. Allogeneic myoblasts transplanted into Duchenne muscular dystrophy (DMD) patients have been, in early trials, largely inefficient owing to immune rejection, rapid death, and limited intramuscular migration–all obstacles that are now being alleviated, at least in part, by more efficient immunosuppression and escalated cell doses. As an alternative to myoblast transplantation, stem cells such as mesoangioblasts and CD133+ progenitors administered through blood circulation have recently shown great potential to regenerate dystrophic muscle.
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: An elastic, biodegradable cardiac patch induces contractile smooth muscle and improves cardiac remodeling and function in subacute myocardial infarction
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Demethylation of the E-cadherin promoter driven by hepatocytes allows for cell fate-determining signals in invasive breast cancer cells
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Stem and Progenitor Cells in Skeletal Muscle Development, Maintenance, and Therapy
Summary: Satellite cells are dormant progenitors located at the periphery of skeletal myofibers that can be triggered to proliferate for both self-renewal and differentiation into myogenic cells. In addition to anatomic location, satellite cells are typified by markers such as M-cadherin, Pax7, Myf5, and neural cell adhesion molecule-1. The Pax3 and Pax7 transcription factors play essential roles in the early specification, migration, and myogenic differentiation of satellite cells. In addition to muscle-committed satellite cells, multi-lineage stem cells encountered in embryonic, as well as adult, tissues exhibit myogenic potential in experimental conditions. These multi-lineage stem cells include side-population cells, muscle-derived stem cells (MDSCs), and mesoangioblasts. Although the ontogenic derivation, identity, and localization of these non-conventional myogenic cells remain elusive, recent results suggest their ultimate origin in blood vessel walls. Indeed, purified pericytes and endothelium-related cells demonstrate high myogenic potential in culture and in vivo. Allogeneic myoblasts transplanted into Duchenne muscular dystrophy (DMD) patients have been, in early trials, largely inefficient owing to immune rejection, rapid death, and limited intramuscular migration-all obstacles that are now being alleviated, at least in part, by more efficient immunosuppression and escalated cell doses. As an alternative to myoblast transplantation, stem cells such as mesoangioblasts and CD133+ progenitors administered through blood circulation have recently shown great potential to regenerate dystrophic muscle.
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Fiber Kinematics of Small Intestinal Submucosa Under Biaxial and Uniaxial Stretch
Summary: Improving our understanding of the design requirements of biologically derived collagenous scaffolds is necessary for their effective use in tissue reconstruction. In the present study, the collagen fiber kinematics of small intestinal submucosa (SIS) was quantified using small angle light scattering (SALS) while the specimen was subjected to prescribed uniaxial or biaxial strain paths. A modified biaxial stretching device based on Billiar and Sacks (J. Biomech., 30, pp. 753–7, 1997) was used, with a real-time analysis of the fiber kinematics made possible due to the natural translucency of SIS. Results indicated that the angular distribution of collagen fibers in specimens subjected to 10% equibiaxial strain was not significantly different from the initial unloaded condition, regardless of the loading path _p=0.31_. Both 10% strip biaxial stretch and uniaxial stretches of greater than 5% in the preferred fiber direction led to an increase in the collagen fiber alignment along the same direction, while 10% strip biaxial stretch in the cross preferred fiber direction led to a broadening of the distribution. While an affine deformation model accurately predicted the experimental findings for a biaxial strain state, uniaxial stretch paths were not accurately predicted. Nonaffine structural models will be necessary to fully predict the fiber kinematics under large uniaxial strains in SIS.
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: The Vascular Wall as a Source of Stem Cells
Summary: We have characterized the emerging hematopoietic system in the human embryo and fetus. Two embryonic organs, the yolk sac and aorta, support the primary emergence of hematopoietic stem cells (HSCs), but only the latter contributes lymphomyeloid stem cells for definitive, adult-type hematopoiesis. A common feature of intra- and extraembryonic hematopoiesis is that in both locations hematopoietic cells emerge in close vicinity to vascular endothelial cells. We have provided evidence that a population of angiohematopoietic mesodermal stem cells, marked by the expression of flk-1 and the novel BB9/ACE antigen, migrate from the paraaortic splanchnopleura into the ventral part of the aorta, where they give rise to hemogenic endothelial cells and, in turn, hematopoietic cells. HSCs also appear to develop from endothelium in the embryonic liver and fetal bone marrow, albeit at a much lower frequency. This would imply that the organism does not function during its whole life on a stock of hematopoietic stem cells established in the early embryo, as is usually accepted. We next examined whether the vessel wall can contribute stem cells for other cell lineages, primarily in the model of adult skeletal muscle regeneration. By immunohistochemistry and flow cytometry, we documented the existence in skeletal muscle, besides genuine endothelial and myogenic cells, of a subset of satellite cells that coexpress endothelial cell markers. This suggested the existence of a continuum of differentiation from vascular cells to endothelial cells that was confirmed in long-term culture. The regenerating capacity of these cells expressing both myogenic and endothelial markers is being investigated in skeletal and cardiac muscle, and the results are being compared with those generated by satellite cells. Altogether, these results point to a generalized progenitor potential of a subset of endothelial, or endothelium-like, cells in blood vessel walls, in pre- and postnatal life.
By The McGowan Institute For Regenerative Medicine | Publication of the Month 2007, Publication of the Month | July 30, 2015
Title: Carbon Monoxide Protects against Hyperoxia-induced Endothelial Cell Apoptosis by Inhibiting Reactive Oxygen Species Formation