Key quality parameter comparison of mesenchymal stem cell product cryopreserved in different cryopreservation solutions for clinical applications.

Introduction: Cryopreservation is a critical process of cell products for achieving a commercial viability through wide scale adoption. By preserving cells in a lower temperature, cryopreservation enables a product to be off-the-shelf and ready for infusion. An optimized cryopreservation strategy can maintain the viability, phenotype, and potency of thawed mesenchymal stromal/stem cells (MSCs) while being regulatory compliant.

Stem cells, cell therapies, and bioengineering in lung biology and diseases 2023.

Repair and regeneration of a diseased lung using stem cells or bioengineered tissues is an exciting therapeutic approach for a variety of lung diseases and critical illnesses. Over the past decade, increasing evidence from preclinical models suggests that mesenchymal stromal cells, which are not normally resident in the lung, can be used to modulate immune responses after injury, but there have been challenges in translating these promising findings to the clinic. In parallel, there has been a surge in bioengineering studies investigating the use of artificial and acellular lung matrices as scaffolds for three-dimensional lung or airway regeneration, with some recent attempts of transplantation in large animal models.

Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis.

Background: In preclinical studies, mesenchymal stromal cells (MSCs), including umbilical cord-derived MSCs (UC-MSCs), demonstrate the ability to modulate numerous pathophysiological processes related to sepsis; however, a systematic synthesis of the literature is needed to assess the efficacy of UC-MSCs for treating sepsis.

Objective: To examine the effects of UC-MSCs on overall mortality (primary outcome) as well as on organ dysfunction, coagulopathy, endothelial permeability, pathogen clearance, and systemic inflammation (secondary outcomes) at prespecified time intervals in preclinical models of sepsis.

Methods: A systematic search was conducted on Embase, Ovid MEDLINE, and Web of Science up to June 20, 2023.

Metabolomics Analysis of Mesenchymal Stem Cell (MSC) Therapy in a Phase I Clinical Trial of Septic Shock: An Exploratory Study.

Sepsis is the result of an uncontrolled host inflammatory response to infection that may lead to septic shock with multiorgan failure and a high mortality rate. There is an urgent need to improve early diagnosis and to find markers identifying those who will develop septic shock and certainly a need to develop targeted treatments to prevent septic shock and its high mortality. Herein, we explore metabolic alterations due to mesenchymal stromal cell (MSC) treatment of septic shock.

Mesenchymal stem cells induce dynamic immunomodulation of airway and systemic immune cells but do not improve survival for mice with H1N1 virus-induced acute lung injury.

Influenza A virus (IAV)-induced acute lung injury (ALI) is characterized by pronounced proinflammatory activation and respiratory lung dysfunction. In this study, we performed deep immune profiling on airway and circulating immune cells to examine the effect of immunomodulation and therapeutic outcomes of mesenchymal stem cells (MSCs) therapy in mice with IAV-induced ALI. Animals were inoculated intranasally with H1N1 IAV, followed by intravenous administration of vehicle, or human clinical-grade, bone marrow-derived MSCs 24-h later, and monitored for six days to evaluate the survival.

Health Disparities in Ovarian Cancer: Report From the Ovarian Cancer Evidence Review Conference.

Health disparity, defined by the Centers for Disease Control and Prevention (CDC) as "preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations," is seen across multiple diseases. We conducted an evidence review of health disparities and inequities and their mitigation strategies related to ovarian cancer as part of a CDC-sponsored project to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. Our review found profound disparities in outcomes such as survival, treatment, and stage at diagnosis by factors such as race and ethnicity, insurance, socioeconomic status, and geographic location.

Executive Summary of the Ovarian Cancer Evidence Review Conference.

The Centers for Disease Control and Prevention awarded funding to the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about ovarian cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in February 2022.

Comparison of freshly cultured versus cryopreserved mesenchymal stem cells in animal models of inflammation: A pre-clinical systematic review.

Background: Mesenchymal stem cells (MSCs) are multipotent cells that demonstrate therapeutic potential for the treatment of acute and chronic inflammatory-mediated conditions. Although controversial, some studies suggest that MSCs may lose their functionality with cryopreservation which could render them non-efficacious. Hence, we conducted a systematic review of comparative pre-clinical models of inflammation to determine if there are differences in in vivo measures of pre-clinical efficacy (primary outcomes) and in vitro potency (secondary outcomes) between freshly cultured and cryopreserved MSCs.

Proceedings of the ISCT scientific signature series symposium, "Advances in cell and gene therapies for lung diseases and critical illnesses": International Society for Cell & Gene Therapy, Burlington VT, US, July 16, 2021.

The ISCT Scientific Signature Series Symposium "Advances in Cell and Gene Therapies for Lung Diseases and Critical Illnesses" was held as an independent symposium in conjunction with the biennial meeting, "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases," which took place July 12-15, 2021, at the University of Vermont. This is the third Respiratory System-based Signature Series event; the first 2, "Tracheal Bioengineering, the Next Steps" and "Cellular Therapies for Pulmonary Diseases and Critical Illnesses: State of the Art of European Science," took place in 2014 and 2015, respectively. Cell- and gene-based therapies for respiratory diseases and critical illnesses continue to be a source of great promise and opportunity.

Poly(I:C) enhances mesenchymal stem cell control of myeloid cells from COVID-19 patients.

Mesenchymal stem cells (MSCs) are being studied for the treatment of COVID-19-associated critical illness, due to their immunomodulatory properties. Here, we hypothesized that viral mimic-priming improves MSCs' abilities to rebalance the dysregulated immune responses in COVID-19. Transcriptome analysis of poly(I:C)-primed MSCs (pIC-MSCs) showed upregulation of pathways in antiviral and immunomodulatory responses.

Mesenchymal stromal (stem) cell therapy modulates miR-193b-5p expression to attenuate sepsis-induced acute lung injury.

Although mesenchymal stromal (stem) cell (MSC) administration attenuates sepsis-induced lung injury in pre-clinical models, the mechanism(s) of action and host immune system contributions to its therapeutic effects remain elusive. We show that treatment with MSCs decreased expression of host-derived microRNA (miR)-193b-5p and increased expression of its target gene, the tight junctional protein occludin (Ocln), in lungs from septic mice. Mutating the Ocln 3' untranslated region miR-193b-5p binding sequence impaired binding to Ocln mRNA.

Gene engineered mesenchymal stem cells: greater transgene expression and efficacy with minicircle vs. plasmid DNA vectors in a mouse model of acute lung injury.

Background: Acute lung injury (ALI) and in its severe form, acute respiratory distress syndrome (ARDS), results in increased pulmonary vascular inflammation and permeability and is a major cause of mortality in many critically ill patients. Although cell-based therapies have shown promise in experimental ALI, strategies are needed to enhance the potency of mesenchymal stem cells (MSCs) to develop more effective treatments. Genetic modification of MSCs has been demonstrated to significantly improve the therapeutic benefits of these cells; however, the optimal vector for gene transfer is not clear.

Immunophenotypic characterization and therapeutics effects of human bone marrow- and umbilical cord-derived mesenchymal stromal cells in an experimental model of sepsis.

Sepsis is a complicated multi-system disorder characterized by a dysregulated host response to infection. Despite substantial progress in the understanding of mechanisms of sepsis, translation of these advances into clinically effective therapies remains challenging. Mesenchymal Stromal Cells (MSCs) possess immunomodulatory properties that have shown therapeutic promise in preclinical models of sepsis.

Mesenchymal Stem/Stromal Cells Increase Cardiac miR-187-3p Expression in a Polymicrobial Animal Model of Sepsis.

Sepsis-induced myocardial dysfunction (MD) is an important pathophysiological feature of multiorgan failure caused by a dysregulated host response to infection. Patients with MD continue to be managed in intensive care units with limited understanding of the molecular mechanisms controlling disease pathogenesis. Emerging evidences support the use of mesenchymal stem/stromal cell (MSC) therapy for treating critically ill septic patients.

Value of mesenchymal stem cell therapy for patients with septic shock: an early health economic evaluation.

Background.: This study estimates the maximum price at which mesenchymal stem cell (MSC) therapy is deemed cost-effective for septic shock patients and identifies parameters that are most important in making treatment decisions.

Methods: We developed a probabilistic Markov model according to the sepsis care trajectory to simulate costs and quality-adjusted life years (QALYs) of septic shock patients receiving either MSC therapy or usual care over their lifetime.

Comparison of freshly cultured versus freshly thawed (cryopreserved) mesenchymal stem cells in preclinical in vivo models of inflammation: a protocol for a preclinical systematic review and meta-analysis.

Background: Mesenchymal stem cells (MSCs) are multipotent cells that demonstrate therapeutic potential for the treatment of acute and chronic inflammatory-mediated conditions. Especially for acute conditions, it is critical to have a readily available freshly thawed (cryopreserved) MSC product for rapid administration. Although controversial, some studies suggest that MSCs may lose their functionality with cryopreservation which in turn could render them non-efficacious.

Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness.

Critical illnesses including sepsis, acute respiratory distress syndromes, ischemic cardiovascular disorders and acute organ injuries are associated with high mortality, morbidity as well as significant health care system expenses. While these diverse conditions require different specific therapeutic approaches, mesenchymal stem/stromal cell (MSCs) are multipotent cells capable of self-renewal, tri-lineage differentiation with a broad range regenerative and immunomodulatory activities, making them attractive for the treatment of critical illness. The therapeutic effects of MSCs have been extensively investigated in several pre-clinical models of critical illness as well as in phase I and II clinical cell therapy trials with mixed results.

Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis.

Background: Characterization of the mesenchymal stromal cell (MSC) safety profile is important as this novel therapy continues to be evaluated in clinical trials for various inflammatory conditions. Due to an increase in published randomized controlled trials (RCTs) from 2012-2019, we performed an updated systematic review to further characterize the MSC safety profile.

Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science (to May 2018) were searched.

Thawed Mesenchymal Stem Cell Product Shows Comparable Immunomodulatory Potency to Cultured Cells In Vitro and in Polymicrobial Septic Animals.

Mesenchymal stem cells (MSCs) have been shown to exert immunomodulatory effects in both acute and chronic diseases. In acute inflammatory conditions like sepsis, cell therapy must be administered within hours of diagnosis, requiring "off-the-shelf" cryopreserved allogeneic cell products. However, their immunomodulatory potency, particularly in abilities to modulate innate immune cells, has not been well documented.

Optimizing imaging of the rat pulmonary microvasculature by micro-computed tomography.

Micro-computed tomography (micro-CT) is used in pre-clinical research to generate high-resolution three-dimensional (3D) images of organs and tissues. When combined with intravascular contrast agents, micro-CT can provide 3D visualization and quantification of vascular networks in many different organs. However, the lungs present a particular challenge for contrast perfusion due to the complexity and fragile nature of the lung microcirculation.

Clinical comparison between neuroendocrine and endometrioid type carcinoma of the uterine corpus.

Objective: To compare the clinicopathologic features and survival outcomes of neuroendocrine tumor of the uterine corpus (NET-U) to endometrioid type endometrial carcinoma (EC).

Methods: From 1993 to 2012, the Surveillance, Epidemiology and End Results cancer registry was queried for women diagnosed with EC or NET-U. Data regarding stage, grade, presence of extra-uterine disease, lymph node metastasis, receipt of adjuvant radiation, surgical intervention and overall survival (OS) was extracted.

Clinicopathologic features, incidence, and survival trends of gynecologic neuroendocrine tumors: a SEER database analysis.

Background: Primary gynecologic neuroendocrine tumors are uncommon malignant neoplasms associated with poor prognosis. Clinically, these tumors present a significant challenge because of the lack of standardized management guidelines.

Objective: The objective of this study is to evaluate the clinicopathologic features, incidence, and survival trends in gynecologic neuroendocrine tumors.

Effects of Mesenchymal Stem Cell Treatment on Systemic Cytokine Levels in a Phase 1 Dose Escalation Safety Trial of Septic Shock Patients.

Objectives: Cellular Immunotherapy for Septic Shock is the first-in-human clinical trial evaluating allogeneic mesenchymal stem/stromal cells in septic shock patients. Here, we sought to determine whether plasma cytokine profiles may provide further information into the safety and biological effects of mesenchymal stem/stromal cell treatment, as no previous study has conducted a comprehensive analysis of circulating cytokine levels in critically ill patients treated with mesenchymal stem/stromal cells.

Design: Phase 1 dose-escalation trial.