Enhancing Mesenchymal Stromal Cell Immunomodulation for Treating Conditions Influenced by the Immune System

Abstract

Mesenchymal stromal cells (MSCs), formerly known as mesenchymal stem cells, are nonhematopoietic multipotent cells and are emerging worldwide as the most clinically used and promising source for allogeneic cell therapy. MSCs, initially obtained from bone marrow, can be derived from several other tissues, such as adipose tissue, placenta, and umbilical cord. Diversity in tissue sourcing and manufacturing procedures has significant effects on MSC products. However, in 2006, a minimal set of standard criteria has been issued by the International Society of Cellular Therapy for defining derived MSCs. These include adherence to plastic in conventional culture conditions, particular phenotype, and multilineage differentiation capacity in vitro. Moreover, MSCs have trophic capabilities, a high in vitro self-renewal ability, and immunomodulatory characteristics. Thus, immunosuppressive treatment with MSCs has been proposed as a potential therapeutic alternative for conditions in which the immune system cells influence outcomes, such as inflammatory and autoimmune diseases. The precise mechanism by which MSCs affect functions of most immune effector cells is not completely understood but involves direct contact with immune cells, soluble mediators, and local microenvironmental factors. Recently, it has been shown that their homeostatic resting state requires activation, which can be achieved in vitro with various cytokines, including interferon-γ. In the present review, we focus on the suppressive effect that MSCs exert on the immune system and highlight the significance of in vitro preconditioning and its use in preclinical studies. We discuss the clinical aspects of using MSCs as an immunomodulatory treatment. Finally, we comment on the risk of interfering with the immune system in regard to cancer formation and development.

Mesenchymal stromal cells for sepsis and septic shock: Lessons for treatment of COVID-19

“…Regarding innate immunity, they notably decrease the production of reactive oxygen species by neutrophils and promote the M2 anti-inflammatory phenotype of macrophages. 9 MSCs influence the phenotype of immune cells and their cytokine secretions. However, this immunomodulation seems to depend on the inflammatory context.…”

“…In an inflammatory context, they inhibit the proliferation of B lymphocytes and their production of immunoglobulins. Regarding innate immunity, they notably decrease the production of reactive oxygen species by neutrophils and promote the M2 anti‐inflammatory phenotype of macrophages 9 …”

Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress

“…Such insight led to first clinical trials, which found transfusion of MSCs contributed to accelerating hematopoietic recovery following high-dose myeloablative chemotherapy and reversing steroid-resistant graft versus host disease (GvHD) [ 26 ], and actual current clinical value of MSCs is primarily derived from immunomodulatory properties (demonstrated in Fig. 1 ), [ 11 , 27 , 28 ]. Since the first clinical trial using MSCs as cellular pharmaceutical agents, numerous clinical trials have been conducted to test the efficacy of MSC-based therapy and over 10,000 of patients have been administered with allogeneic or autologous MSCs for the treatment of various diseases [ 21 , 29 ] (Mesenchymal stem cells search at www.clinicaltrials.gov , accessed on 24 April 2020), including GvHD, myocardial infarction (MI), stroke, Crohn’s disease, multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), diabetes, lupus, arthritis, acute lung injury, Covid-19 [ 30 ], cirrhosis, and so on.…”

Implantable Therapeutic Reservoir Systems for Diverse Clinical Applications in Large Animal Models

“…Cell therapy encompasses a broad clinical territory in which transplanted cells are used to terminate or reverse an assortment of disease processes, such as cardiovascular disease, [ 1,2 ] diabetes, [ 3 ] autoimmune disorders, [ 4 ] neurodegenerative disease, [ 5,6 ] and cancer. [ 7 ] The last decade has seen an exponential advancement of cell therapy technologies, with promising preclinical results finally yielding substantial clinical benefit using Chimeric Antigen Receptor T‐cell (CAR T) for treatment of hematologic malignancies.…”