Robust Expansion of Hematopoietic Stem Cells Ex Vivo Using Small Molecule Cocktails.

The insufficient number of hematopoietic stem cells (HSCs) poses a significant challenge for successful hematopoietic stem cell transplantation and gene-based therapies. To address this issue, ex vivo expansion of HSCs has been developed, improving engraftment and reducing morbidity risks in hematological disorders. Small molecules, known as stem cell agonists (SCAs), have been utilized to promote HSC expansion and have been implemented in clinical trials.

Impact of lower concentrations of dimethyl sulfoxide on cryopreservation of autologous hematopoietic stem cells: a systematic review and meta-analysis of controlled clinical studies.

Background Aims: Cryopreservation of hematopoietic stem cells (HSCs) is crucial for autologous transplantation, cord blood banking and other special circumstances. Dimethyl sulfoxide (DMSO) is used most commonly for cryopreserving HSC products but can cause infusional toxicities and affect cell viability and engraftment after transplant. A systematic review of controlled studies using lower concentrations of DMSO to cryopreserve HSC products in clinical transplant studies is needed to determine the effect of reducing DMSO concentrations on post-thaw cell viability, initial engraftment and adverse effects on patient health.

Homing and Engraftment of Hematopoietic Stem Cells Following Transplantation: A Pre-Clinical Perspective.

Hematopoietic stem-cell (HSC) transplantation (HSCT) is used to treat various hematologic disorders. Use of genetically modified mouse models of hematopoietic cell transplantation has been critical in our fundamental understanding of HSC biology and in developing approaches for human patients. Pre-clinical studies in animal models provide insight into the journey of transplanted HSCs from infusion to engraftment in bone-marrow (BM) niches.

AA2P-mediated DNA demethylation synergizes with stem cell agonists to promote expansion of hematopoietic stem cells.

Small molecules have enabled expansion of hematopoietic stem and progenitor cells (HSPCs), but limited knowledge is available on whether these agonists can act synergistically. In this work, we identify a stem cell agonist in AA2P and optimize a series of stem cell agonist cocktails (SCACs) to help promote robust expansion of human HSPCs. We find that SCACs provide strong growth-promoting activities while promoting retention and function of immature HSPC.

Humoral and Cellular Response of Transplant Recipients to a Third Dose of mRNA SARS-CoV-2 Vaccine: A Systematic Review and Meta-analysis.

Background: High rates of nonresponse to 2 doses of mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine have been reported in transplant recipients. Several studies have investigated the efficacy of a third dose in this population. However, efficacy remains unclear, as response rates vary across studies.

Clinical Outcomes of Umbilical Cord Blood Transplantation Using Ex Vivo Expansion: A Systematic Review and Meta-Analysis of Controlled Studies.

Greater use of umbilical cord blood (UCB) for hematopoietic cell transplantation (HCT) is limited by the number of cells in banked units. Ex vivo culture strategies have been increasingly evaluated in controlled studies, but their impact on transplantation-related outcomes remains uncertain owing to the small patient numbers in these studies, necessitating an updated systematic review and meta-analysis. A systematic literature search was conducted using the MEDLINE, Embase, and Cochrane databases to March 18, 2022.

Use of CRISPR/Cas9 gene editing to improve chimeric antigen-receptor T cell therapy: A systematic review and meta-analysis of preclinical studies.

Background: Chimeric antigen-receptor T (CAR-T) cells represent great promise in cancer treatment. CRISPR/Cas9 gene editing in preclinical studies has enabled the development of enhanced CAR-T products with improved function and reduced toxicity.

Methods: A systematic review of preclinical animal studies was conducted to determine the efficacy and safety of this approach.

MSC-Derived Extracellular Vesicles in Preclinical Animal Models of Bone Injury: A Systematic Review and Meta-Analysis.

Background And Objective: Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) are a promising treatment for bone injuries, although studies remain preclinical. A systematic review and meta-analysis can assess the efficacy of MSC-EVs and identify treatment aspects associated with enhanced bone repair.

Methods: English language, preclinical, controlled, in vivo studies identified in our systematic search (up to May 8, 2020) examining the use of MSC-EVs in bone healing were included.

MSC-Derived Extracellular Vesicles to Heal Diabetic Wounds: a Systematic Review and Meta-Analysis of Preclinical Animal Studies.

Introduction: Extracellular vesicles from mesenchymal stromal cells (MSC-EVs) have shown promise in wound healing. Their use in diabetic wounds specifically, however, remains pre-clinical and their efficacy remains uncertain less clear. A systematic review of preclinical studies is needed to determine the efficacy of MSC-EVs in the treatment of diabetic wounds to accelerate the clinical translation of this cell-based therapy.

Persistence of CRISPR/Cas9 gene edited hematopoietic stem cells following transplantation: A systematic review and meta-analysis of preclinical studies.

Gene editing blood-derived cells is an attractive approach to cure selected monogenic diseases but remains experimental. A systematic search of preclinical controlled studies is needed to determine the persistence of edited cells following reinfusion. All studies identified in our systematic search (to 20 October 2020) examining the use of CRISPR/Cas9 gene editing in blood-derived cells for transplantation were included.

The γ-Protocadherins Regulate the Survival of GABAergic Interneurons during Developmental Cell Death.

Inhibitory interneurons integrate into developing circuits in specific ratios and distributions. In the neocortex, inhibitory network formation occurs concurrently with the apoptotic elimination of a third of GABAergic interneurons. The cell surface molecules that select interneurons to survive or die are unknown.

Plerixafor in combination with chemotherapy and/or hematopoietic cell transplantation to treat acute leukemia: A systematic review and metanalysis of preclinical and clinical studies.

Leukemia-initiating cells localize to bone marrow niches via cell surface CXCR4 binding to stromal-derived factor 1 (SDF-1). Plerixafor, a CXCR4 antagonist, can mobilize and sensitize leukemia cells to cytotoxic therapy, and/or enhance the engraftment of healthy donor stem cells in the context of hematopoietic cell transplantation (HCT). A systematic review of preclinical and clinical studies was performed (updated May 1, 2020) to inform the design of definitive clinical trials and identified 19 studies.

Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to Chemotherapy.

Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that metal response element binding transcription factor 2/polycomblike 2 (MTF2/PCL2) plays a fundamental role in the polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML.

Mtf2-PRC2 control of canonical Wnt signaling is required for definitive erythropoiesis.

Polycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 to specific genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions.

Micro-RNA Profiling of Exosomes from Marrow-Derived Mesenchymal Stromal Cells in Patients with Acute Myeloid Leukemia: Implications in Leukemogenesis.

Gene regulatory networks in AML may be influenced by microRNAs (miRs) contained in exosomes derived from bone marrow mesenchymal stromal cells (MSCs). We sequenced miRs from exosomes isolated from marrow-derived MSCs from patients with AML (n = 3) and from healthy controls (n = 3; not age-matched). Known targets of mIRs that were significantly different in AML-derived MSC exosomes compared to controls were identified.

Clinical and tree hollow populations of human pathogenic yeast in Hamilton, Ontario, Canada are different.

Yeast are among the most frequent pathogens in humans. The dominant yeast causing human infections belong to the genus Candida and Candida albicans is the most frequently isolated species. However, several non-C.

Is low-level laser therapy in relieving neck pain effective? Systematic review and meta-analysis.

The aim of this study is to determine the efficacy of low-level laser therapy (LLLT) in reducing acute and chronic neck pain as measured by the visual analog scale (VAS). A systematic search of nine electronic databases was conducted to identify original articles. For study selection, two reviewers independently assessed titles, abstracts, and full text for eligibility.

Ecological structuring of yeasts associated with trees around Hamilton, Ontario, Canada.

This study seeks to determine the distribution and diversity of yeasts in and around the Hamilton area in Canada. In light of the increasing number of fungal infections along with rising morbidity and mortality rates, especially among the immunocompromised, understanding the diversity and distribution of yeasts in natural environments close to human habitations has become an increasingly relevant topic. In this study, we analyzed 1110 samples obtained from the hollows of trees, shrubs and avian droppings at 8 geographical sites in and around Hamilton, Ontario, Canada.

Prevalent nosocomial clusters among causative agents for candidemia in Hamilton, Canada.

In Canada, the incidence of candidemia, the bloodstream infection caused by Candida species, varied from 1.2-5.1 cases/100,000, representing the third most common type of bloodstream infections in intensive care unit patients.