Effects of blood donor characteristics and storage on red blood cell haemoglobin β S-nitrosylation.

Background And Objectives: In the setting of tissue hypoxia, S-nitrosylated haemoglobin (SNO-Hb) plays crucial roles in the control of blood flow. This is associated with decreased oxygen affinity to haemoglobin and increase in tissue oxygenation. Red blood cell (RBC) transfusion is primarily performed to improve tissue oxygenation in anaemic patients.

CellKine clinical trial: first report from a phase 1 trial of allogeneic bone marrow-derived mesenchymal stem cells in subjects with painful lumbar facet joint arthropathy.

Background: Lumbar facet joint arthropathy (LFJA) is a major cause of low back pain (LBP), with current treatments offering limited long-term benefits. Bone marrow-derived mesenchymal stem cells (BM-MSCs) show promise due to their immunomodulatory and trophic effects, potentially addressing underlying degenerative processes in LFJA.

Objectives: This initial report describes the outcomes of the first treated patient in an ongoing mutidisciplinary phase 1 clinical trial evaluating the safety and feasibility of intra-articular allogeneic BM-MSCs for painful LFJA.

Discoveries from human stem cell research in space that are relevant to advancing cellular therapies on Earth.

Stem cell research performed in space has provided fundamental insights into stem cell properties and behavior in microgravity including cell proliferation, differentiation, and regeneration capabilities. However, there is broader scientific value to this research including potential translation of stem cell research in space to clinical applications. Here, we present important discoveries from different studies performed in space demonstrating the potential use of human stem cells as well as the limitations in cellular therapeutics.

Secretome from iPSC-derived MSCs exerts proangiogenic and immunosuppressive effects to alleviate radiation-induced vascular endothelial cell damage.

Background: Radiation therapy is the standard of care for central nervous system tumours. Despite the success of radiation therapy in reducing tumour mass, irradiation (IR)-induced vasculopathies and neuroinflammation contribute to late-delayed complications, neurodegeneration, and premature ageing in long-term cancer survivors. Mesenchymal stromal cells (MSCs) are adult stem cells that facilitate tissue integrity, homeostasis, and repair.

Phase 1, Dose Escalation, Nonrandomized, Open-Label, Clinical Trial Evaluating the Safety and Preliminary Efficacy of Allogenic Adipose-Derived Mesenchymal Stem Cells for Recurrent Glioblastoma: A Clinical Trial Protocol.

Background And Objectives: Despite standard of care with maximal safe resection and chemoradiation, glioblastoma is the most common and aggressive type of primary brain cancer. Surgical resection provides a window of opportunity to locally treat gliomas while the patient is recovering, and before initiating concomitant chemoradiation. To assess the safety and establish the maximum tolerated dose of adipose-derived mesenchymal stem cells (AMSCs) for the treatment of recurrent glioblastoma (GBM).

In Vitro Enhanced Osteogenic Potential of Human Mesenchymal Stem Cells Seeded in a Poly (Lactic--Glycolic) Acid Scaffold: A Systematic Review.

Study Design: Human bone marrow stem cells (hBMSCs) and human adipose-derived stem cells (hADSCs) have demonstrated the capability to regenerate bone once they have differentiated into osteoblasts.

Objective: This systematic review aimed to evaluate the in vitro osteogenic differentiation potential of these cells when seeded in a poly (lactic--glycolic) acid (PLGA) scaffold.

Methods: A literature search of 4 databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in January 2021 for studies evaluating the osteogenic differentiation potential of hBMSCs and hADSCs seeded in a PLGA scaffold.

Mesenchymal Stromal Cell Healing Outcomes in Clinical and Pre-Clinical Models to Treat Pressure Ulcers: A Systematic Review.

Background: Despite numerous measures used to prevent pressure ulcers, their growing prevalence in recent years is expected to continue as the population ages. This review aims to report the outcomes of the regenerative potential of MSCs in treating pressure ulcers, assessing the effectiveness of MSCs in treating pressure ulcers.

Methods: A computerized search for articles on animal models that use MSCs as primary therapy to treat pressure ulcers, published from conception to present, was conducted using PubMed, MEDLINE, Embase, and CINAHL.

Mesenchymal Stem Cell Therapy in Acute Intracerebral Hemorrhage: A Dose-Escalation Safety and Tolerability Trial.

Background: We conducted a preliminary phase I, dose-escalating, safety, and tolerability trial in the population of patients with acute intracerebral hemorrhage (ICH) by using human allogeneic bone marrow-derived mesenchymal stem/stromal cells.

Methods: Eligibility criteria included nontraumatic supratentorial hematoma less than 60 mL and Glasgow Coma Scale score greater than 5. All patients were monitored in the neurosciences intensive care unit for safety and tolerability of mesenchymal stem/stromal cell infusion and adverse events.

Bone Morphogenic Protein and Mesenchymal Stem Cells to Regenerate Bone in Calvarial Defects: A Systematic Review.

Background: The use of bone morphogenic protein and mesenchymal stem cells has shown promise in promoting bone regeneration in calvarial defects. However, a systematic review of the available literature is needed to evaluate the efficacy of this approach.

Methods: We comprehensively searched electronic databases using MeSH terms related to skull defects, bone marrow mesenchymal stem cells, and bone morphogenic proteins.

Diabetic kidney disease induces transcriptome alterations associated with angiogenesis activity in human mesenchymal stromal cells.

Background: Therapeutic interventions that optimize angiogenic activities may reduce rates of end-stage kidney disease, critical limb ischemia, and lower extremity amputations in individuals with diabetic kidney disease (DKD). Infusion of autologous mesenchymal stromal cells (MSC) is a promising novel therapy to rejuvenate vascular integrity. However, DKD-related factors, including hyperglycemia and uremia, might alter MSC angiogenic repair capacity in an autologous treatment approach.

How do we assess batch-to-batch consistency between extracellular vesicle products?

Background: Extracellular vesicles (EVs) have gained interest in the field of regenerative and transfusion medicine. Specifically, current Good Manufacturing Practice (cGMP)-grade EVs produced by mesenchymal stromal cells (MSCs) are an intriguing option for cell-free therapeutics. With the development of cGMP-grade EV products, a simple and reliable method for batch-to-batch consistency is needed.

Feasibility and Safety of Low-Dose Mesenchymal Stem Cell Infusion in Lung Transplant Recipients.

Background: We have previously shown bone marrow-derived mesenchymal stem cells (MSCs) may shift immune responses toward anti-inflammatory pathways and stabilize the course of obstructive chronic lung allograft syndrome (o-CLAD) after lung transplantation. In this study, we measured the response of lower dose infusions.

Methods: We infused low-dose MSCs intravenously in 13 patients who had developed moderate-to-severe o-CLAD.

Mesenchymal stem cell therapy for focal epilepsy: A systematic review of preclinical models and clinical studies.

Drug-resistant epilepsy (DRE) is characterized by recurrent seizures despite appropriate treatment with antiseizure medication (ASM). Due to their regenerative and immunomodulatory potential, therapies with biologics such as mesenchymal stem cells (MSCs) offer a potential therapeutic benefit for structural causes of epilepsy, such as hippocampal sclerosis. In this article, we report a systematic review of the literature evaluating the preclinical and clinical studies of MSCs for DRE.

Considerations for immune effector cell therapy collections: a white paper from the American Society for Apheresis.

Background Aims: This white paper was developed to provide leukapheresis guidance for the collection of mononuclear cells from adult and pediatric patients who are destined for immune effector cell (IEC) therapies for commercial and research applications. Currently, there is considerable variability in leukapheresis processes and limited published information regarding best practices relevant to new cellular therapies, especially IECs. Herein the authors address critical leukapheresis questions in five domains to help guide consistent collection processes and ensure high-quality products.

Hypoxia-preconditioning of human adipose-derived stem cells enhances cellular proliferation and angiogenesis: A systematic review.

Background: Human adipose-derived stem cells (hADSCs) have gained attention lately because of their ease of harvesting and ability to be substantially multiplied in laboratory cultures. Stem cells are usually cultured under atmospheric conditions; however, preconditioning stem cells under hypoxic conditions seems beneficial.

Aim: This systematic review aims to investigate the effect of hypoxia preconditioning and its impact on the proliferation and angiogenic capacity of the hADSCs.

Lack of defined apheresis collection criteria in publicly available CAR-T cell clinical trial descriptions: Comprehensive review of over 600 studies.

Background: Chimeric antigen receptor T (CAR-T) cell successes have encouraged continued clinical study. Apheresis collection of starting material for CAR-T cell therapy product manufacturing is critical but described approaches suggest variability and clinical guidelines are currently lacking. The goal of this study was to gather and assess variability in apheresis collection descriptions in publicly available CAR T-cell therapy clinical trials.

Development and evaluation of IL-6 overexpressing mesenchymal stem cells (MSCs).

Mesenchymal stem/stromal cell (MSC) therapy has been investigated in multiple diseases and conditions. Although the mechanisms of MSC-based therapies are not fully understood, we and others have shown interleukin 6 (IL-6) to be an important factor in MSC function. IL-6 contributes to many biological events, such as immune response, neurogenesis, and bone remodeling.

Endothelial nitric oxide synthase-engineered mesenchymal stromal cells induce anti-inflammation in experimental immune models.

Background Aims: Mesenchymal stromal cells (MSCs) remain an area of interest in the field of regenerative medicine. Although there is clear evidence of safety, a lack of substantial efficacy has led to many MSC-based clinical trials to stall in phase 1. Therefore, potentiating MSCs with biologically relevant messenger RNA (mRNA) transcripts presents a relatively safe and efficient way to increase functionality.

IL-10 mRNA Engineered MSCs Demonstrate Enhanced Anti-Inflammation in an Acute GvHD Model.

Mesenchymal stem cells (MSCs) are used in various studies to induce immunomodulatory effects in clinical conditions associated with immune dysregulation such as graft versus host disease (GvHD). However, most of these clinical trials failed to go beyond early phase 2 studies because of limited efficacy. Various methods have been assessed to increase the potency of MSCs.

Application of Human Adipose-Derived Stem cells for Bone Regeneration of the Skull in Humans.

Background: Archeological archives report cranioplasty as 1 of the oldest surgical procedures; however, it was not until the last century that true advances have been made. Alternative approaches are necessary to achieve optimal closure of the defect with fewer adverse effects. We aim to evaluate the use of human adipose-derived stem cells (hADSCs) alone or seeded in scaffolds as the main treatment for cranial bone defects and to assess human patient outcomes.