Vascular endothelium as a novel source of stem cells for bioengineering

Susienka, Michael; Medici, Damian

doi:10.4161/biom.24647

Cited by 12 publications

(5 citation statements)

References 35 publications

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“…As the failure of the BBB is a crucial early occurrence in MS pathogenesis, any therapy that overcomes BBB dysfunction and reestablishes functional ability without the risk of collateral long-term immunotoxic effects may well offer a new paradigm as a first-line treatment for MS patients. [41] Given the clinically significant improvement in participant performance in this study, it is plausible that the BM-MNSCs replaced and repaired degenerated endothelial tissue associated with dysfunction of the blood-brain barrier (through an angiogenic mechanism) [42] , counteracted nerve damage and promoted rapid neurogenesis (e.g., by propelling oligodendrocyte progenitor cells [OPCs]), which is consistent with previous research. [2,36,[43][44][45][46] Double-blind, placebo-controlled clinical trials are needed to support the efficacy of any new treatment.…”

Section: Discussionsupporting

confidence: 88%

The Effectiveness of Selective Stem Cell Placement on Gait Performance in Patients with Multiple Sclerosis: a Phase I Clinical Trial

Cohen

Broeska

2019

Int. J. Pharm. Sci. Drug Res.

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Multiple sclerosis (MS) is a chronic and oftentimes disabling disease of the central nervous system. It affects almost 1 million people living in the United States and about 2.5 million people globally. Though the cause is not fully understood, MS occurs through an inflammatory process in the brain. This inflammation results in the destruction of the myelin sheath surrounding the nerves that enable conduction of nerve impulses within the brain and spinal cord. To overcome symptoms, MS patients are usually prescribed disease modifying drug therapies or immunosuppressive drugs for prolonged periods resulting in only temporary clinical improvement. In a large subset of patients, disease progression is measured by the continuing deterioration of physical ability. One of the most reliable measures of disease progression in MS is gait performance. Previous studies have demonstrated that clinically significant gait deviations occur at all stages of MS that involve walking. This report describes a Phase I clinical trial of a novel targeted delivery technique, selectively placing autologous bone marrow mononuclear stem cells into the central vein of multiple sclerosis patients, with post-operative functional changes measured by gait performance. To determine the functional benefit of selective stem cell placement, the timed 25-foot walk was administered to 31 MS patients before and after therapy. The time and number of steps taken to complete the test significantly decreased post-intervention. Currently, disease-modifying and immunosuppressive drugs are the only approved treatments for MS. Comparative trials between disease-modifying and immunosuppressive drugs measure benefit as a slowing of multiple sclerosis manifestations, not an improvement. This trial demonstrated an immediate global improvement in the level of disability as measured by the timed 25-foot walk. This suggests that recovery of function in MS patients is possible. Where pharmaceutical agents only mitigate symptoms and potentially slow disease progression, selective stem cell placement of autologous bone marrow mononuclear stem cells should be considered as a possible treatment for MS due to measured improvement in post-therapy functional ability. Further research is required to validate our findings.

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Section: Discussionsupporting

confidence: 88%

The Effectiveness of Selective Stem Cell Placement on Gait Performance in Patients with Multiple Sclerosis: a Phase I Clinical Trial

Cohen

Broeska

2019

Int. J. Pharm. Sci. Drug Res.

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“…Other conditions in which EndoMT has been implicated are sporadic (Sun et al, ) and hereditary heterotopic ossification (Medici et al, ), Kawasaki disease (He et al, ) and vein graft rejections (Cooley et al, ). In addition to a pathological role, the therapeutic potential of EndoMT has been explored as part of tissue engineering in regenerative medicine (Susienka and Medici, ; Medici, ).…”

Section: Discussionmentioning

confidence: 99%

Endothelial‐to‐mesenchymal transition in cardiovascular diseases: Developmental signaling pathways gone awry

Sánchez‐Duffhues

Vinuesa

Dijke

2017

Developmental Dynamics

128

113

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The process named endothelial-to-mesenchymal transition (EndMT) was observed for the first time during the development of the chicken embryo several decades ago. Of interest, accumulating evidence suggests that EndMT plays a critical role in the onset and progression of multiple postnatal cardiovascular diseases. EndMT is controlled by a set of developmental signaling pathways, very similar to the process of epithelial-to-mesenchymal transition, which determine the activity of several EndMT transcriptional effectors. Once activated, these EndMT effectors regulate the expression of endothelial-and mesenchymalspecific genes, in part by interacting with specific motifs in promoter regions, eventually leading to the down-regulation of endothelial-specific features and acquisition of a fibroblast-like phenotype. Important technical advances in lineage tracing methods combined with experimental mouse models demonstrated the pathophysiological importance of EndMT for human diseases. In this review, we discuss the major signal transduction pathways involved in the activation and regulation of the EndMT program. Furthermore, we will review the latest discoveries on EndMT, focusing on cardiovascular diseases, and in particular on its role in vascular calcification, pulmonary arterial hypertension, and organ fibrosis. Developmental Dynamics 247:492-508,

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“…In fact, blood vessels are believed to originate from endothelial precursors (Carmeliet, 2005). Another important characteristic of ECs that contributes to tissue engineering is their plasticity and, consequently, their ability to dedifferentiate into stem cells when stimulated to undergo endothelial-mesenchymal transition, which makes them a potential cell source for use in regenerative strategies, as reviewed elsewhere (Susienka and Medici, 2013).…”

Section: Endothelial Cells and Endothelial Progenitor Cell Populationsmentioning

confidence: 99%

Cellular strategies to promote vascularisation in tissue engineering applications

Costa‐Almeida

Granja²,

Soares³

et al. 2014

eCM

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Vascularisation is considered to be one of the greatest challenges in tissue engineering. Different strategies exist but cell-based approaches have emerged as a promising therapy to achieve successful vascularisation. The use of endothelial cells to engineer vascularised tissues has been extensively investigated. This field of research has evolved with the discovery of endothelial progenitor cells, a subpopulation with a high regenerative potential. However, the survival of endothelial cell populations alone seems to be impaired. To overcome this problem, co-culture systems, involving supporting cells, like mural cells, fibroblasts, or more tissue-specific cells have been developed. Endothelial cells benefit from the extracellular matrix components and growth factors produced by the supporting cells, which results in neovessel stabilisation and maturation. The use of endothelial progenitor cells in co-culture systems appears to be a promising strategy to promote vascularisation in approaches of increasing complexity. Herein, the authors provide an overview of the cellular strategies that can be used for increasing vascularisation in tissue engineering and regeneration.

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Vascular endothelium as a novel source of stem cells for bioengineering

Cited by 12 publications

References 35 publications

The Effectiveness of Selective Stem Cell Placement on Gait Performance in Patients with Multiple Sclerosis: a Phase I Clinical Trial

The Effectiveness of Selective Stem Cell Placement on Gait Performance in Patients with Multiple Sclerosis: a Phase I Clinical Trial

Endothelial‐to‐mesenchymal transition in cardiovascular diseases: Developmental signaling pathways gone awry

Cellular strategies to promote vascularisation in tissue engineering applications

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