CAR-NK cells to treat patients with cancer: a systematic scoping review of published studies and registered clinical trials.

Introduction: Chimeric antigen-receptor natural killer cells (CAR-NKs) offer a promising allogeneic immune effector cell therapy to treat malignant diseases. A systematic review is needed to understand the scope of current clinical studies and registered active trials to identify aspects of study design and cell product characterization that could accelerate greater clinical adoption.

Methods: A systematic review of all publications (to January 25, 2025) and registered clinical trials (to June 21, 2024) was conducted.

Use of non-qualifying umbilical cord blood units to support research and quality assurance by the Canadian Blood Services Cord Blood Bank.

Background: Umbilical cord blood units collected by Canadian Blood Services for public banking at selected collection hospitals may not meet stringent criteria for release to the bank's inventory and can be used to support research. The Cord Blood for Research Program (CB4RP) was established when the CBS bank was established, but the breadth of research activity supported by the CB4RP has not been previously described.

Methods: Records of projects and units requested to support research were reviewed and summarized from September 2014 to October 2024.

The Passage of Chaperonins to Extracellular Locations in Requires a Functional Dot/Icm System.

HtpB, the chaperonin of the bacterial pathogen , is found in extracellular locations, even the cytoplasm of host cells. Although chaperonins have an essential cytoplasmic function in protein folding, HtpB exits the cytoplasm to perform extracellular virulence-related functions that support 's lifestyle. The mechanism by which HtpB reaches extracellular locations is not currently understood.

Obesity modulates NK cell activity via LDL and DUSP1 signaling for populations with adverse social determinants.

African American (AA) women are disproportionately affected by obesity and hyperlipidemia, particularly in the setting of adverse social determinants of health (aSDoH) that contribute to health disparities. Obesity, hyperlipidemia, and aSDoH appear to impair NK cells. As potential common underlying mechanisms are largely unknown, we sought to investigate common signaling pathways involved in NK cell dysfunction related to obesity and hyperlipidemia in AA women from underresourced neighborhoods.

Recruiting blood donors to the Canadian Blood Services Stem Cell Registry: A feasibility assessment.

Background: Allogeneic hematopoietic cell transplantation remains limited when stem cell registrants cannot be contacted, are not medically fit, are unavailable, or unwilling to proceed. In a recent report, registrants who were prior blood donors were more likely to be available for donation. In this study, we analyzed extent to which recruiting blood donors to the Canadian Blood Services Stem Cell Registry (CBS SCR) can meet targets for ethnic diversity, age, and proximity to collection facilities.

Optimizing Access to Unrelated Donors in Canada: Re-Examining the Importance of Donor Factors on Outcomes Following Hematopoietic Cell Transplantation.

HLA-matched allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for many patients. Unrelated HLA-matched donors are the most frequently used donor for HCT. When more than one donor transplant option is available, transplant centers can select donors based on non-HLA factors.

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.

Hematopoietic Cell Transplantation Trends and Outcomes in Canada: A Registry-Based Cohort Study.

Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centres in Canada.

HLA-haplotype redundancy and rareness in Canadian Blood Services' Stem Cell Registry and Cord Blood Bank: Novel metrics for optimizing utility.

Background: The utility of unrelated donor registries that support allogeneic hematopoietic cell transplantation could be optimized through greater understanding of redundancy and rareness of HLA phenotypes.

Methods: HLA phenotype rareness was determined using known HLA haplotype frequencies. Donor redundancy was determined through pairwise comparison of donor HLA profiles within an inventory.

Registered clinical trials investigating treatment with cell-derived extracellular vesicles: a scoping review.

Background Aims: Interest in cell-based therapy using extracellular vesicles (EVs) is intensifying, building upon promising preclinical research and a handful of published clinical studies. Registered clinical trials remain small, heterogeneous in design and underpowered to determine safety and efficacy on their own. A scoping review of registered studies can identify opportunities to pool data and perform meta-analysis.

The Effect of the COVID-19 Pandemic on Unrelated Allogeneic Hematopoietic Donor Collections and Safety.

Background And Objectives: The COVID-19 pandemic profoundly influenced unrelated donor (UD) allogeneic peripheral blood stem cell (PBSC) collections. Changes included efforts to minimize COVID-19 exposure to donors and cryopreservation of products. The extent to which the efficacy and safety of PBSC donations were affected by the pandemic is unknown.

Modeling unrelated blood stem cell donor recruitment using simulated registrant cohorts: Assessment of human leukocyte antigen matching across ethnicity groups.

Background: Human leukocyte antigen (HLA)-matched unrelated donors are not available for some patients considered for allogeneic hematopoietic cell transplantation, particularly among certain ethnic groups. Simulated recruitment modeling can inform efforts to find new matches for more patients.

Methods: Simulated recruits were generated by assigning a pair of donor HLA haplotypes from historical data files and matched against HLA data of patient searches in the Canadian Blood Services Stem Cell Registry.

A Portrait of Cord Blood Units Distributed for Transplantation from Canadian Blood Services' Cord Blood Bank: First Analysis.

Background: The Canadian Blood Services Cord Blood Bank (CBS CBB) was created to improve access to stem cell products for transplantation for patients across ethnic groups. An analysis of distributed units is needed to assess the effectiveness of the bank to meet the needs of patients from different ethnic groups.

Methods: A descriptive analysis was performed on all cord blood units distributed from the CBS' CBB as of 30 June 2022.

Iron Chelator DIBI Suppresses Formation of Ciprofloxacin-Induced Antibiotic Resistance in .

Antibiotic resistance of bacterial pathogens results from their exposure to antibiotics and this has become a serious growing problem that limits effective use of antibiotics. Resistance can arise from mutations induced by antibiotic-mediated damage with these mutants possessing reduced target sensitivity. We have studied ciprofloxacin (CIP)-mediated killing of and the influence of the Reactive Oxygen Species (ROS) inactivator, thiourea and the iron chelator DIBI, on initial killing by CIP and their effects on survival and outgrowth upon prolonged exposure to CIP.

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.

Systematic review and meta-analysis of randomized controlled trials of mesenchymal stromal cells to treat coronavirus disease 2019: is it too late?

Background Aims: Evidence regarding the extent that mesenchymal stromal cells (MSCs) may improve clinical outcomes in patients with coronavirus disease 2019 (COVID-19) has been limited by marked inter-study heterogeneity, inconsistent product characterization and appreciable risk of bias (RoB). Given the evolution of treatment options and trajectory of the pandemic, an updated analysis of high-quality evidence from randomized controlled trials is needed for a timely and conclusive understanding of the effectiveness of MSCs.

Methods: A systematic literature search through March 30, 2022, identified all English language, full-text randomized controlled trials examining the use of MSCs in the treatment of COVID-19.

Can GCSF-stimulated donor lymphocyte infusions improve outcomes for relapsed disease following allogeneic hematopoietic cell transplantation? A systematic review and meta-analysis.

Donor lymphocyte infusions (DLI) can produce graft-versus tumor effects to treat relapse after allogeneic hematopoietic cell transplantation, however, durable responses remain uncommon. A systematic review and meta-analysis are needed to clarify whether DLI collected after stimulation with granulocyte colony-stimulating factor (GCSF; G-DLI) can improve clinical outcomes. Sixteen studies (4 controlled) involving 585 patients were identified in a systematic search up to 17 September 2020.

Updated Living Systematic Review and Meta-analysis of Controlled Trials of Mesenchymal Stromal Cells to Treat COVID-19: A Framework for Accelerated Synthesis of Trial Evidence for Rapid Approval-FASTER Approval.

Background: Mesenchymal stromal cells (MSCs) may reduce mortality in patients with COVID-19; however, early evidence is based on few studies with marked interstudy heterogeneity. The second iteration of our living systematic review and meta-analysis evaluates a framework needed for synthesizing evidence from high-quality studies to accelerate consideration for approval.

Methods: A systematic search of the literature was conducted on November 15, 2021, to identify all English-language, full-text, and controlled clinical studies examining MSCs to treat COVID-19 (PROSPERO: CRD42021225431).

The Hunt Is On! In Pursuit of the Ideal Stem Cell Population for Cartilage Regeneration.

Cartilage injury and degeneration are hallmarks of osteoarthritis (OA), the most common joint disease. OA is a major contributor to pain, loss of function, and reduced quality of life. Over the last decade, considerable research efforts have focused on cell-based therapies, including several stem cell-derived approaches to reverse the cartilage alterations associated with OA.

Demand and usage of unrelated donor products for allogeneic haematopoietic cell transplantation during the COVID-19 pandemic: A Canadian Blood Services Stem Cell Registry analysis.

Background And Objectives: Understanding changes in the demand and usage of unrelated allogeneic haematopoietic cell transplantation (HCT) donors during the COVID-19 pandemic is needed to optimize pandemic preparedness of registry and donor collection services. The aim of this study was to understand the extent to which the pandemic has impacted the demand and usage of unrelated donors and cord blood units (CBUs) at Canadian Blood Services (CBS).

Materials And Methods: Data regarding stem cell donor interest and product usage for unrelated allogeneic HCT were retrieved from the database at CBS using de-identified anonymous information.

Systematic Scoping Review of Studies Reporting Unexpected Donor-Derived Abnormalities from Recipients of Allogeneic Hematopoietic Cell Transplantation: A Proposed Framework for Donor Disclosure.

Allogeneic hematopoietic cell transplantation (HCT) is used increasingly to treat blood and immune-based disorders. Post-transplantation testing of HCT recipients can lead to unexpected molecular, cytogenetic, and other information in donor-derived cells, raising questions regarding the potential impact on donor health. This study was conducted to identify the breadth of donor-derived abnormalities identified by testing HCT recipients and to determine the extent to which disclosure and donor follow-up are described.

Mesenchymal stem/stromal cell-based therapies for COVID-19: First iteration of a living systematic review and meta-analysis: MSCs and COVID-19.

Background: Mesenchymal stem/stromal cells (MSCs) and their secreted products are a promising therapy for COVID-19 given their immunomodulatory and tissue repair capabilities. Many small studies were launched at the onset of the pandemic, and repeated meta-analysis is critical to obtain timely and sufficient statistical power to determine efficacy.

Methods And Findings: All English-language published studies identified in our systematic search (up to February 3, 2021) examining the use of MSC-derived products to treat patients with COVID-19 were identified.

A Portrait of SARS-CoV-2 Infection in Patients Undergoing Hematopoietic Cell Transplantation: A Systematic Review of the Literature.

The management of COVID-19 in hematopoietic cell transplant (HCT) recipients represents a special challenge given the variable states of immune dysregulation and altered vaccine efficacy in this population. A systematic search (Ovid Medline and Embase on 1 June 2021) was needed to better understand the presenting features, prognostic factors, and treatment options. Of 897 records, 29 studies were identified in our search.