stem cell law

Endogenous tags have become invaluable tools to visualize and study native proteins in live cells. However, generating human cell lines carrying endogenous tags is difficult due to the low efficiency of homology-directed repair. Recently, an engineered split mNeonGreen protein was used to generate a large-scale endogenous tag library in HEK293 cells. Using split mNeonGreen for large-scale endogenous tagging in human iPSCs would open the door to studying protein function in healthy cells and across differentiated cell types...

Treosulfan has shown promise in allogeneic hematopoietic cell transplantation (HCT) for its myeloablative properties and low toxicity. In this single-center retrospective propensity score-matched cohort study we compared treosulfan- and busulfan-based conditioning in allogeneic HCT for patients with myelodysplastic syndrome (MDS). This study included 138 adults who underwent allogeneic HCT for MDS or chronic myelomonocytic leukemia (CMML) at Princess Margaret Hospital, Toronto 2015-2022. Using propensity score matching, we compared transplant outcomes between two well-matched cohorts who received conditioning with either fludarabine-treosulfan (FT) (n=46) or fludarabine-busulfan with total body irradiation (FBT200) (n=92)...

Various groups including animal protection organizations, medical organizations, research centers, and even federal agencies such as the U.S. Food and Drug Administration, are working to minimize animal use in scientific experiments. This movement primarily stems from animal welfare and ethical concerns. However, recent advances in technology and new studies in medicine have contributed to an increase in animal experiments throughout the years. With the rapid increase in animal testing, concerns arise including ethical issues, high cost, complex procedures, and potential inaccuracies...

BACKGROUND AND OBJECTIVES: Stem cell banking (SCB) is a promising area of modern medicine with the potential to yield innovative treatments and cures. To effectively educate parents and implement laws and regulations that address parental concerns and encourage informed decision-making, it is imperative to emphasize parental viewpoints and their consequences for future healthcare. The study aims to establish the Saudi Arabian population's level of understanding regarding SCB and to comprehend the elements influencing parental knowledge, attitudes, and SCB decision-making processes...

The carboxy-terminus of the spliceosomal protein PRPF8, which regulates the RNA helicase Brr2, is a hotspot for mutations causing retinitis pigmentosa-type 13, with unclear role in human splicing and tissue-specificity mechanism. We used patient induced pluripotent stem cells-derived cells, carrying the heterozygous PRPF8 c.6926 A > C (p.H2309P) mutation to demonstrate retinal-specific endophenotypes comprising photoreceptor loss, apical-basal polarity and ciliary defects. Comprehensive molecular, transcriptomic, and proteomic analyses revealed a role of the PRPF8/Brr2 regulation in 5'-splice site (5'SS) selection by spliceosomes, for which disruption impaired alternative splicing and weak/suboptimal 5'SS selection, and enhanced cryptic splicing, predominantly in ciliary and retinal-specific transcripts...

Embryogenesis requires substantial coordination to translate genetic programs to the collective behavior of differentiating cells, but understanding how cellular decisions control tissue morphology remains conceptually and technically challenging. Here, we combine continuous Cas9-based molecular recording with a mouse embryonic stem cell-based model of the embryonic trunk to build single-cell phylogenies that describe the behavior of transient, multipotent neuro-mesodermal progenitors (NMPs) as they commit into neural and somitic cell types...

Measure declares that patients can be given unapproved treatments.

OBJECTIVE: To study the histopathological staging of atrophic lesions of the gastric mucosa. METHODS: Histology and immunohistochemistry were used to closely examine 2144 specimens of atrophic gastric mucosa that were taken from endoscopic biopsies. RESULTS: When the gastric mucosa epithelium is affected by infection, chemical stimulation, immune factors, genetic factors, and other factors, it may cause an atrophy of gastric mucosa epithelium and a decrease in the number of glands, intestinal metaplasia, hyperplasia of smooth muscle fibers, and atrophy of stem cells in the proliferative zone...

This is a consensus-based Canadian guideline whose primary purpose is to standardize and facilitate the management of chronic graft-versus-host disease (cGvHD) across the country. Creating uniform healthcare guidance in Canada is a challenge for a number of reasons including the differences in healthcare authority structure, funding and access to healthcare resources between provinces and territories, as well as the geographic size. These differences can lead to variable and unequal access to effective therapies for GvHD...

Introduction: Muscle and bone constitute the two main parts of the musculoskeletal system and generate an intricately coordinated motion system. The crosstalk between muscle and bone has been under investigation, leading to revolutionary perspectives in recent years. Method and results: In this review, the evolving concept of muscle-bone interaction from mechanical coupling, secretory crosstalk to stem cell exchange was explained in sequence. The theory of mechanical coupling stems from the observation that the development and maintenance of bone mass are largely dependent on muscle-derived mechanical loads, which was later proved by Wolff's law, Utah paradigm and Mechanostat hypothesis...

PURPOSE: To guide the vaccination of adults with solid tumors or hematologic malignancies. METHODS: A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and nonrandomized studies on the efficacy and safety of vaccines used by adults with cancer or their household contacts. This review builds on a 2013 guideline by the Infectious Disease Society of America. PubMed and the Cochrane Library were searched from January 1, 2013, to February 16, 2023...

In order to study early human development while avoiding the burdens associated with human embryo research, scientists are redirecting their efforts towards so-called human embryo-like structures (hELS). hELS are created from clusters of human pluripotent stem cells and seem capable of mimicking early human development with increasing accuracy. Notwithstanding, hELS research finds itself at the intersection of historically controversial fields, and the expectation that it might be received as similarly sensitive is prompting proactive law reform in many jurisdictions, including the Netherlands...

Human pluripotent stem cells, such as human embryonic stem cells and human induced pluripotent stem cells, are used in basic research and various applied fields, including drug discovery and regenerative medicine. Stem cell technologies have developed rapidly in recent years, and the supply of culture materials has improved. This has facilitated the culture of human pluripotent stem cells and has enabled an increasing number of researchers and bioengineers to access this technology. At the same time, it is a challenge to share the basic concepts and techniques of this technology among researchers and technicians to ensure the reproducibility of research results...

The ideal immunosuppressive agents to complement post-transplant cyclophosphamide (PTCy) in PBSC-based haploidentical hematopoietic cell transplantation (haplo-HCT) remain debated. This study looks at our experience with ATG-PTCy-Cyclosporine (CsA) prophylaxis in PB haplo-HCT since 2015. Between October 2015 and December 2021, 157 adults underwent haploidentical hematopoietic cell transplantation (haplo-HCT) using a GVHD prophylaxis regimen comprising rabbit-ATG, PTCy, and CsA. Among these patients, 76.4% received a total ATG dose of 4...

The premature marketing of investigational stem cell interventions (SCIs) is a growing market in the US. Several US states have passed legislation to permit and promote unproven and experimental SCIs for individuals with terminal or chronic diseases. These SCI medical freedom laws, which are largely based on right-to-try legislation, increase access to experimental SCIs with little to no oversight. They undermine federal regulatory authority and can compromise patient safety and informed decision-making. SCI medical freedom laws have gone largely unnoticed by scientific societies interested in the responsible translation of stem cell medicine...

Fifty years ago, Dr. John Laragh brought forward the "vasoconstriction-volume hypothesis" of hypertension. This is Ohm's Law in blood pressure regulation, explicating hypertension as a consequence of increased peripheral vascular resistance, cardiac output, or both. Resistance vessels, those of a diameter less than 200 μm, determines mean arterial pressure by controlling peripheral vascular resistance. In comparison, large capacitance arteries, particularly the aorta, confines the systolic and diastolic blood pressure in physiological range through the "windkessel effect"...

BACKGROUND: Metabolic dysfunction is one of the main symptoms of Werner syndrome (WS); however, the underlying mechanisms remain unclear. Here, we report that loss of WRN accelerates adipogenesis at an early stage both in vitro (stem cells) and in vivo (zebrafish). Moreover, WRN depletion causes a transient upregulation of late-stage of adipocyte-specific genes at an early stage. METHODS: In an in vivo study, we generated wrn-/- mutant zebrafish and performed histological stain and Oil Red O staining to assess the fat metabolism...

Recent experimental evidence strongly supports that three-dimensional (3D) long-range enhancer-promoter (E-P) interactions have important influences on gene-expression dynamics, but it is unclear how the interaction information is translated into gene expression over time (4D). To address this question, we developed a general theoretical framework (named as a 4D nucleome equation), which integrates E-P interactions on chromatin and biochemical reactions of gene transcription. With this equation, we first present the distribution of mRNA counts as a function of the E-P genomic distance and then reveal a power-law scaling of the expression level in this distance...

The mechanical properties of cells are closely related to their physiological states and functions. Due to the limitations of conventional cell elasticity measurement technologies such as low throughput, cell-invasiveness, and high cost, microfluidic systems are emerging as powerful tools for high-throughput cell mechanical property studies. This paper introduces a microfluidic system to automatically measure the elastic modulus of single cells in real time. The system integrated a microfluidic chip with a microchannel for cell constriction, a pressure pump, a precision differential pressure sensor, and a program for online analysis of cell deformation...

Mounting evidence suggests metabolism instructs stem cell fate decisions. However, how fetal metabolism changes during development and how altered maternal metabolism shapes fetal metabolism remain unexplored. We present a descriptive atlas of in vivo fetal murine metabolism during mid-to-late gestation in normal and diabetic pregnancy. Using 13 C-glucose and liquid chromatography-mass spectrometry (LC-MS), we profiled the metabolism of fetal brains, hearts, livers, and placentas harvested from pregnant dams between embryonic days (E)10...