Cocaine-Induced Microglial Impairment and Its Rehabilitation by PLX-PAD Cell Therapy.

Chronic cocaine use triggers inflammatory and oxidative processes in the central nervous system, resulting in impaired microglia. Mesenchymal stem cells, known for their immunomodulatory properties, have shown promise in reducing inflammation and enhancing neuronal survival. The study employed the cocaine self-administration model, focusing on ionized calcium-binding adaptor protein 1 (Iba-1) and cell morphology as markers for microglial impairment and PLX-PAD cells as a treatment for attenuating cocaine craving.

An Integrative Pediatric Oncology Program Addressing Parents' Quality of Life-Related Concerns.

Background: Parents of children with cancer face bio-psycho-social-spiritual concerns which can significantly reduce quality of life (QoL). We examined the impact of an integrative oncology (IO) intervention on QoL-related concerns among parents of children in a pediatric hematology-oncology department.

Measures: The study was prospective, controlled, nonrandomized and patient-preferenced.

PACE: randomized, controlled, multicentre, multinational, phase III study of PLX-PAD for critical limb ischaemia in patients unsuitable for revascularization: randomized clinical trial.

Background: Revascularization is the primary treatment modality for chronic limb-threatening ischaemia (CLTI), but is not feasible in all patients. PLX-PAD is an off-the-shelf, placental-derived, mesenchymal stromal cell-like cell therapy. This study aimed to evaluate whether PLX-PAD would increase amputation-free survival in people with CLTI who were not candidates for revascularization.

Gaps in pediatric oncologic end of life care as recounted by the bereaved parents in Isarel.

Purpose: This study investigated parents' perception of their needs and those of their children with cancer at the end-of-life period, including unmet needs and their expectations regarding providers.

Design And Methods: This cross-sectional study involved 26 parents recruited from three pediatric hematology-oncology wards in Israel who completed demographic and medical questionnaires of the child, and a parental needs questionnaire based on The Needs Assessment of Family Caregivers-Cancer questionnaire, following the death of their child.

Findings: Parents expressed needs related to medical care, including pain management, decision-making, and finding optimal treatment options for their children.

Challenges in Implementing Guideline on Integrative Oncology and Pain: The Israeli Perspective.

Context And Objectives: To explore the feasibility of implementing the joint guideline on integrative medicine for pain management in oncology, published by the Society for Integrative Oncology (SIO) and the American Society of Clinical Oncology (ASCO), for integrative oncology (IO) services in supportive and palliative care.

Methods: A qualitative research methodology was co-designed by the SIO-ASCO guideline committee, with the Society for Complementary Medicine, Israel Medical Association (IMA). A questionnaire with five open-ended questions exploring barriers and enablers to implementing the guideline was distributed to chairs and board members of nine IMA-affiliated medical societies; four deans of Israeli medical schools; and nurses from the Israeli Society for Oncology Nursing.

Special Issue "Stem Cell Biology & Regenerative Medicine".

More than 50% of pre-clinical studies fail despite a long and expensive journey of drug discovery using animal models [...

Functional defects in hiPSCs-derived cardiomyocytes from patients with a PLEKHM2-mutation associated with dilated cardiomyopathy and left ventricular non-compaction.

Dilated cardiomyopathy (DCM) is a primary myocardial disease, leading to heart failure and excessive risk of sudden cardiac death with rather poorly understood pathophysiology. In 2015, Parvari's group identified a recessive mutation in the autophagy regulator, PLEKHM2 gene, in a family with severe recessive DCM and left ventricular non-compaction (LVNC). Fibroblasts isolated from these patients exhibited abnormal subcellular distribution of endosomes, Golgi apparatus, lysosomes and had impaired autophagy flux.

Death spiral of the legacy grid: A game-theoretic analysis of modern grid defection processes.

Decreasing costs of distributed generation and storage, alongside increasing network charges, provide consumers with a growing incentive to defect from the main grid. On a large scale, this may lead to price inflation, hindrance of the energy transition, and even a "death spiral" - a domino effect of disconnections. Here, we develop a game-theoretic framework that demonstrates how conflicting interests among consumers - an aspect that previous studies overlooked - may lead to complex dynamics of grid defection.

hiPSC-Derived Cells as Models for Drug Discovery 2.0.

Human-induced pluripotent stem cells (hiPSCs) serve as a sustainable resource for studying the molecular foundation of disease development, including initiation and deterioration [...

On the gain of entrainment in the -dimensional ribosome flow model.

The ribosome flow model (RFM) is a phenomenological model for the flow of particles along a one-dimensional chain of sites. It has been extensively used to study ribosome flow along the mRNA molecule during translation. When the transition rates along the chain are time-varying and jointly -periodic the RFM entrains, i.

PLEKHM2 Loss of Function Impairs the Activity of iPSC-Derived Neurons via Regulation of Autophagic Flux.

Pleckstrin Homology And RUN Domain Containing M2 (PLEKHM2) [delAG] mutation causes dilated cardiomyopathy with left ventricular non-compaction (DCM-LVNC), resulting in a premature death of PLEKHM2[delAG] individuals due to heart failure. PLEKHM2 is a factor involved in autophagy, a master regulator of cellular homeostasis, decomposing pathogens, proteins and other cellular components. Autophagy is mainly carried out by the lysosome, containing degradation enzymes, and by the autophagosome, which engulfs substances marked for decomposition.

Pre-Administration of PLX-R18 Cells Protects Mice from Radiation-Induced Hematopoietic Failure and Lethality.

Acute Radiation Syndrome (ARS) is a syndrome involving damage to multiple organs caused by exposure to a high dose of ionizing radiation over a short period of time; even low doses of radiation damage the radiosensitive hematopoietic system and causes H-ARS. PLacenta eXpanded (PLX)-R18 is a 3D-expanded placenta-derived stromal cell product designated for the treatment of hematological disorders. These cells have been shown in vitro to secrete hematopoietic proteins, to stimulate colony formation, and to induce bone marrow migration.

Higher Loading of Gold Nanoparticles in PAD Mesenchymal-like Stromal Cells Leads to a Decreased Exocytosis.

Cell therapy is an important new method in medicine and is being used for the treatment of an increasing number of diseases. The challenge here is the precise tracking of cells in the body and their visualization. One method to visualize cells more easily with current methods is their labeling with nanoparticles before injection.

Placenta-Derived Mesenchymal-like Adherent Stromal Cells as an Effective Cell Therapy for Cocaine Addiction in a Rat Model.

Recent research points to mesenchymal stem cells' potential for treating neurological disorders, especially drug addiction. We examined the longitudinal effect of placenta-derived mesenchymal stromal-like cells (PLX-PAD) in a rat model for cocaine addiction. Sprague-Dawley male rats were trained to self-administer cocaine or saline daily until stable maintenance.

HIPGEN: a randomized, multicentre phase III study using intramuscular PLacenta-eXpanded stromal cells therapy for recovery following hip fracture arthroplasty : a study design.

Aims: The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

Methods: HIPGEN is a multicentre, multinational, randomized, double-blind, placebo-controlled trial. A total of 240 patients aged 60 to 90 years with low-energy femoral neck fractures (FNF) will be allocated to two arms and receive an intramuscular injection of either 150 × 10 PLX-PAD cells or placebo into the medial gluteal muscle after direct lateral implantation of total or hemi hip arthroplasty.

A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation.

Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nano-sized EVs from therapy-grade human placental-expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology.

Intramuscular and intratendinous placenta-derived mesenchymal stromal-like cell treatment of a chronic quadriceps tendon rupture.

Background: Quadriceps tendon ruptures (QTRs) are rare but debilitating injuries, often associated with chronic metabolic conditions or long-term steroid treatment. While the surgical treatment for acute QTRs is described thoroughly, no common strategy exists for the often frustrating treatment of chronic, reoccurring QTRs. The pro-angiogenic and immunomodulatory properties of placenta-derived adherent mesenchymal stromal-like (PLX-PAD) cells have been described to protect musculoskeletal tissues from inflammation and catabolic cytokine migration, yet little is known about the regenerative potential of PLX-PAD cells in repetitively damaged tendon tissue.

The Effect of Sera from Children with Obstructive Sleep Apnea Syndrome (OSAS) on Human Cardiomyocytes Differentiated from Human Embryonic Stem Cells.

Obstructive sleep apnea syndrome (OSAS) patients suffer from cardiovascular morbidity, which is the leading cause of death in this disease. Based on our previous work with transformed cell lines and primary rat cardiomyocytes, we determined that upon incubation with sera from pediatric OSAS patients, the cell's morphology changes, NF-κB pathway is activated, and their beating rate and viability decreases. These results suggest an important link between OSAS, systemic inflammatory signals and end-organ cardiovascular diseases.

RESTORE Survey on the Public Perception of Advanced Therapies and ATMPs in Europe-Why the European Union Should Invest More!

Advanced therapy medicinal products (ATMPs) are potential game changers in modern medical care with an anticipated major impact for patients and society. They are a new drug class often referred to as "living drugs," and are based on complex components such as vectors, cells and even tissues. The production of such ATMPs involves innovative biotechnological methods.

hiPSC-Derived Cells as Models for Drug Discovery.

More than 85% of pre-clinically tested drugs fail during clinical trials, which results in a long, inefficient and costly process, suggesting that animal models are often poor predictors of human biology [...

Generation and characterization of three human induced pluripotent stem cell lines (iPSC) from two family members with dilated cardiomyopathy and left ventricular noncompaction (DCM-LVNC) and one healthy heterozygote sibling.

Autophagy serves as a master regulator of cellular homeostasis. Hence, expectedly autophagic dysfunction has been documented in many diseases such as cancer, neurodegeneration and cardiovascular disorders. A novel homozygous mutation in PLEKHM2 gene (mPLEKHM2) resulted in dilated cardiomyopathy with left ventricular noncompaction (DCM-LVNC), probably as result of impaired autophagy due to disruption of lysosomal movement assisted by PLEKHM2.

Placenta-Expanded Stromal Cell Therapy in a Rodent Model of Simulated Weightlessness.

Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative.

Perinatal Cells: A Promising COVID-19 Therapy?

The COVID-19 pandemic has become a priority in the health systems of all nations worldwide. In fact, there are currently no specific drugs or preventive treatments such as vaccines. The numerous therapies available today aim to counteract the symptoms caused by the viral infection that in some subjects can evolve causing acute respiratory distress syndromes (ARDS) with consequent admission to intensive care unit.

Placenta-Derived Cell Therapy to Treat Patients With Respiratory Failure Due to Coronavirus Disease 2019.

Objectives: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019.

Design: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020.

Setting: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey.

Generation of iPSC lines from two (BGUi002-A and BGUi003-A) homozygous p450 oxidoreductase-deficient patients and from one (BGUi001-A) heterozygous healthy family relative.

p450 oxidoreductase (POR) cytochromes are enzymes involved in the metabolism of steroids and sex hormones, in which POR acts as an electron donor. Inactivating mutations in the POR gene cause diverse deficiencies. Access to patient samples carrying these POR mutations can contribute to the understanding of metabolic and developmental processes.