Adelheid Weidinger

Ludwig Boltzmann Institute for Traumatology

Many preclinical studies have shown that birth-associated tissues, cells and their secreted factors, otherwise known as perinatal derivatives (PnD), possess various biological properties that make them suitable therapeutic candidates for the treatment of numerous pathological conditions. Nevertheless, in the field of PnD research, there is a lack o...

The human amniotic membrane (hAM) has been used in tissue regeneration. A promising alternative is the usage of cell-derived bioactive factors released from the viable native hAM. Regarding the EVs derived from hAM, only little information is available. The aim of this study is to characterize EVs derived from preconditioned human amniotic membrane...

Dopa-responsive dystonia (DRD) and Parkinson's disease (PD) are movement disorders caused by the dysfunction of nigrostriatal dopaminergic neurons. Identifying druggable pathways and biomarkers for guiding therapies is crucial due to the debilitating nature of these disorders. Recent genetic studies have identified variants of GTP cyclohydrolase-1...

Mitochondrial ROS (mitoROS) control many reactions in cells. Biological effects of mitoROS in vivo can be investigated by modulation via mitochondria-targeted antioxidants (mtAOX, mitoTEMPO). The aim of this study was to determine how mitoROS influence redox reactions in different body compartments in a rat model of endotoxemia. We induced inflamma...

The human amniotic membrane (hAM) has been recognized as promising source of therapeutic cells in tissue regeneration, namely human amniotic membrane mesenchymal stromal cells and human amniotic membrane epithelial cells, which have been attributed with stem cell characteristics. Procedures such as cell isolation and differentiation may lead to the...

Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases, represents an important goal in improving human health. Here, we show that the lipid synthesis enzyme phosphatidylethanolamine cytidyltransfer...

Brain injury is accompanied by neuroinflammation, accumulation of extracellular glutamate and mitochondrial dysfunction, all of which cause neuronal death. The aim of this study was to investigate the impact of these mechanisms on neuronal death. Patients from the neurosurgical intensive care unit suffering aneurysmal subarachnoid hemorrhage (SAH)...

Perinatal derivatives or PnDs refer to tissues, cells and secretomes from perinatal, or birth-associated tissues. In the past 2 decades PnDs have been highly investigated for their multimodal mechanisms of action that have been exploited in various disease settings, including in different cancers and infections. Indeed, there is growing evidence th...

Muscle degeneration is the most prevalent cause for frailty and dependency in inherited diseases and ageing, affecting hundreds of millions of people. Elucidation of pathophysiological mechanisms, as well as effective treatments for muscle diseases represents an important goal in improving human health. Here, we show that phosphatidylethanolamine c...

Mitochondria-targeted antioxidants (mtAOX) are a promising treatment strategy against reactive oxygen species-induced damage. Reports about harmful effects of mtAOX lead to the question of whether these could be caused by the carrier molecule triphenylphosphonium (TPP). The aim of this study was to investigate the biological effects of the mtAOX mi...

Facioscapulohumeral muscular dystrophy (FSHD) is characterised by descending skeletal muscle weakness and wasting. FSHD is caused by mis-expression of the transcription factor DUX4, which is linked to oxidative stress, a condition especially detrimental to skeletal muscle with its high metabolic activity and energy demands. Oxidative damage charact...

Design and development of novel nanobiomaterials with multifunctional properties hold the promise of new therapeutic strategies to improve the current clinical research in the field of tissue engineering and regenerative medicine. Here, we have successfully synthesized novel autofluorescent hydroxyapatite (HAP) using a template-assisted assembly pr...

Facioscapulohumeral muscular dystrophy (FSHD) is characterised by descending skeletal muscle weakness and wasting. FSHD is caused by mis-expression of the transcription factor DUX4, which is linked to oxidative stress, a condition especially detrimental to skeletal muscle with its high metabolic activity and energy demands. Oxidative damage charact...

For more than 100 years, the human amniotic membrane (hAM) has been used in multiple tissue regeneration applications. The hAM consists of cells with stem cell characteristics and a rich layer of extracellular matrix. Undoubtedly, the hAM with viable cells has remarkable properties such as the differentiation potential into all three germ layers, i...

Background Cerebral ischemia and neuroinflammation following aneurysmal subarachnoid hemorrhage (SAH) are major contributors to poor neurological outcome. Our study set out to investigate in an exploratory approach the interaction between NO and energy metabolism following SAH as both hypoxia and inflammation are known to affect nitric oxide (NO) m...

Reactive oxygen species (ROS) have recently been recognized as important signal transducers, particularly regulating proliferation and differentiation of cells. Diphenyleneiodonium (DPI) is known as an inhibitor of the nicotinamide adenine dinucleotide phosphate oxidase (NOX) and is also affecting mitochondrial function. The aim of this study was t...

Progress in the understanding of the biology of perinatal tissues has contributed to the breakthrough revelation of the therapeutic effects of perinatal derivatives (PnD), namely birth-associated tissues, cells, and secreted factors. The significant knowledge acquired in the past two decades, along with the increasing interest in perinatal derivati...

Photobiomodulation (PBM), especially in the red wavelength range, has been demonstrated to be an effective treatment option for superficial and chronic wounds. However, ischemia and subsequent reperfusion can further challenge wound healing. Therefore, we investigated the effect of pulsed red LED light at 635 nm on cellular function in an in-vitro...

Amniotic cells show exciting stem cell features, which has led to the idea of using living cells of human amniotic membranes (hAMs) in toto for clinical applications. However, under common cell culture conditions, viability of amniotic cells decreases rapidly, whereby reasons for this decrease are unknown so far. Recently, it has been suggested tha...

Background Evidence suggests that early adaptive responses of hepatic mitochondria occur in experimentally induced sepsis. Little is known about both colonic mitochondrial function during abdominal infection and long-term changes in mitochondrial function under inflammatory conditions. We hypothesize that hepatic and colonic mitochondrial oxygen co...

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.

Despite great leaps in tissue engineering development, the human amniotic membrane (hAM), a natural biomaterial, is still in the race. The discovery that cells of the hAM possess stem cell characteristics created new options for the clinical use of hAM for tissue regeneration. Furthermore, cell organelles, such as mitochondria, have recently been r...

Despite great leaps in tissue engineering development, the human amniotic membrane (hAM), a natural biomaterial, is still in the race. The discovery that cells of the hAM possess stem cell characteristics created new options for the clinical use of hAM for tissue regeneration. Furthermore, cell organelles, such as mitochondria, have recently been r...

Osteoarthritis (OA) is one of the most common causes of disability and represents a major socio-economic burden. Despite intensive research, the molecular mechanisms responsible for the initiation and progression of OA remain inconclusive. In recent years experimental findings revealed elevated levels of reactive oxygen species (ROS) as a major fac...

Genetic regulators and environmental stimuli modulate T cell activation in autoimmunity and cancer. The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine neurotransmitters, the generation of nitric oxide, and pain1,2. Here we uncover a link between these processes, identifying a fundamental role for BH4 in T cell...

The human amniotic membrane (hAM) has been used for tissue regeneration for over a century. In vivo (in utero), cells of the hAM are exposed to low oxygen tension (1-4% oxygen), while the hAM is usually cultured in atmospheric, meaning high, oxygen tension (20% oxygen). We tested the influence of oxygen tensions on mitochondrial and inflammatory pa...

Background and purpose: Based on the fact that traumatic brain injury is associated with mitochondrial dysfunction we aimed at localization of mitochondrial defect and attempted to correct it by thiamine. Experimental approach: Interventional controlled experimental animal study was used. Adult male Sprague-Dawley rats were subjected to lateral...

Over a century ago, clinicians started to use the human amniotic membrane for coverage of wounds and burn injuries. To date, literally thousands of different clinical applications exist for this biomaterial almost exclusively in a decellularized or denuded form. Recent reconsiderations for the use of vital human amniotic membrane for clinical appli...

Background: Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino-acid, and innate immunity changes in children with sepsis. Methods: Sixty-eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy cont...

Supplemental Material - Cellular and Site-Specific Mitochondrial Characterization of Vital Human Amniotic Membrane

Increased levels of nitric oxide (NO) and peroxynitrite (ONOO‒), mitochondrial dysfunction at complex I, and excessive accumulation of glutamate have been suggested as the key pathophysiological events leading to brain damage upon traumatic brain injury (TBI). The aim of this study was to delineate the relationship between these three events and to...

Although mitochondrial dysfunction is commonly accepted to mediate organ failure induced by systemic inflammatory response (SIR) the data on impairment of mitochondrial respiration upon SIR are still controversial. The aim of this study was to understand the contribution of mitochondrial reactive oxygen species (mtROS) to liver failure induced by S...

Mitochondrial-derived reactive oxygen species have been deemed an important contributor in sepsis pathogenesis. We investigated whether two mitochondria-targeted antioxidants (mtAOX; SkQ1 and MitoTEMPO) improved long-term outcome, lessened inflammation, and improved organ homeostasis in polymicrobial murine sepsis. 3-month-old female CD-1 mice ( n=...

Liver failure induced by systemic inflammatory response (SIRS) is often associated with mitochondrial dysfunction but the mechanism linking SIRS and mitochondria-mediated liver failure is still a matter of discussion. Current hypotheses suggest that causative events could be a drop in ATP synthesis, opening of mitochondrial permeability transition...

Supplementary Fig. 1. Score sheet for a custom-developed mouse clinical assessment scoring system. The well-being of mice is assessed based on six endpoints every 12 hours (beginning at 12h post-CLP); tree severity grades (i.e. 0, 1 or 2 points) are assigned. Euthanasia is indicated when: score ≥8 and/or by inability to trigger the startle reflex a...

Systemic inflammatory response (SIR) is a defense reaction of the body against pathogens, but it can also cause damage to host tissues. Recently we have shown that this damage can be effectively reduced by inhibition of mitochondrial reactive oxygen species (mtROS) generation. Specific aim of this study was to clarify whether or not acute phase inf...

Purpose: To develop an assay that can enable the quantification of intra- and extracellular nitric oxide (NO) levels in liver biopsies without application of potentially harmful exogenous NO traps. Theory: Electron paramagnetic resonance (EPR) spectroscopy is currently the most appropriate method of measuring NO in biological samples due to the...

Nitric oxide (NO) has frequently been associated with secondary damage after brain injury. However, average NO levels in different brain regions before and after traumatic brain injury (TBI) and its role in post-TBI mitochondrial dysfunction remain unclear. In this comprehensive profiling study, we demonstrate for the first time that basal NO level...

Nitrite protects various organs from ischemia-reperfusion injury by ameliorating mitochondrial dysfunction. Here we provide evidence that this protection is due to the inhibition of iron-mediated oxidative reactions caused by the release of iron ions upon hypoxia. We show in a model of isolated rat liver mitochondria that upon hypoxia mitochondria...

Nitrite protects various organs from ischemia-reperfusion injury by ameliorating mitochondrial dysfunction. Here we provide evidence that this protection is due to the inhibition of iron-mediated oxidative reactions caused by the release of iron ions upon hypoxia. We show in a model of isolated rat liver mitochondria that upon hypoxia, mitochondria...

Introduction: Systemic inflammatory response syndrome (SIRS) is a highly complex cascade of pro- and anti-inflammatory mechanisms, which results in a generalized activation of the immune system. Reactive oxygen species (ROS) and mitochondria, as one of the major sources of them play a key role in this process. Considering the deleterious effects o...

Introduction: Systemic inflammation is associated with an excessive production of nitric oxide (NO), which interferes with a number of metabolic pathways, including mitochondrial ATP synthesis. Methods: We examined seventy-eight adult patients (severe sepsis (SS)/22; non-infectious systemic inflammatory response (SIRS)/23; healthy (H)/33). Energ...

Introduction: Nitric oxide (NO) is a potent signaling molecule maintaining numerous physiological and pathophysiological processes. Because of its short lifespan, the detection of NO by electron paramagnetic resonance spectroscopy (EPR) in frozen tissues requires stabilization by specific exogenous NO-traps. Such NO-traps are unfeasible in clinica...

Introduction: Altered mitochondrial function by excessive production of reactive oxygen species (ROS) has been considered an important factor in pathogenesis of organ failure in sepsis. Methods: We investigated effects of two specific mitochondria-targeted antioxidants (SkQ1: lipophilic; MitoTEMPO: hydrophilic) on outcome, inflammatory response...

Mitochondrial dysfunction is assumed to be an important contributor to multi organ dysfunction syndrome. Here, the effects of varying degrees of sepsis on hepatic mitochondrial function were investigated. Moderate or more severe sepsis was induced in rats using a colon ascendens stent peritonitis (CASP)-model (16G and 14G stent respectively). Respi...

In the past, reactive oxygen and nitrogen species (RONS) were shown to cause oxidative damage to biomolecules, contributing to the development of a variety of diseases. However, recent evidence has suggested that intracellular RONS are an important component of intracellular signaling cascades. The aim of this review was to consolidate old and new...

The mechanisms of sepsis mortality remain undefined. While there is some evidence of organ damage, it is not clear whether this damage alone is sufficient to cause death. Therefore, we aimed to examine contribution of organ injury/dysfunction to early deaths in the mouse abdominal sepsis. Female OF-1 mice underwent either medium-severity cecal liga...

Aims: Increasing evidences suggest that, apart from activation of guanylyl cyclase, intracellular nitric oxide (NO) signaling is associated with an interaction between NO and reactive oxygen species (ROS) to modulate physiological or pathophysiological processes. The aim of this study was to understand the contribution of mitochondrial ROS (mtROS)...

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Background: Traumatic brain injury (TBI) is accompanied by increased glutamate excitotoxicity, nitric oxide levels, and mitochondrial dysfunction. The aim of this study was to clarify whether these events are