From the Guidelines
Mesenchymal stem cells (MSCs) should not be used for intravascular delivery without proper hemocompatibility screening and anticoagulation treatment due to the risk of severe adverse events, including thrombosis and embolization, as reported in several studies 1.
Definition and Characteristics of MSCs
Mesenchymal stem cells (MSCs) are multipotent adult stem cells found in various tissues including bone marrow, adipose tissue, umbilical cord, and dental pulp. These cells have the remarkable ability to differentiate into multiple cell types including bone, cartilage, muscle, and fat cells. MSCs are characterized by their fibroblast-like morphology, plastic adherence in culture, and expression of specific surface markers such as CD73, CD90, and CD105, while lacking hematopoietic markers like CD45, as defined by the International Society for Cell Therapy (ISCT) 1.
Therapeutic Effects and Clinical Applications
Beyond their differentiation capacity, MSCs possess immunomodulatory properties, secreting various cytokines and growth factors that can suppress inflammation, promote tissue repair, and enhance regeneration. This has made them valuable candidates for cell-based therapies treating conditions like osteoarthritis, graft-versus-host disease, and various inflammatory disorders. MSCs exert their therapeutic effects primarily through paracrine signaling rather than direct cell replacement, releasing extracellular vesicles containing bioactive molecules that influence surrounding tissues.
Safety Concerns and Recommendations
However, the use of MSCs for intravascular delivery has raised concerns about their safety, particularly with regards to their potential to trigger the instant blood-mediated inflammatory reaction (IBMIR) and cause thrombosis and embolization 1. Therefore, it is essential to standardize isolation methods, expansion protocols, and delivery systems, and to use anticoagulation treatment and hemocompatibility screening to minimize the risk of adverse events. The use of low-dose anticoagulants such as heparin in the clinical setting is also recommended, if applicable 1.
Some key points to consider when using MSCs for clinical applications include:
- The tissue source of MSCs, with bone marrow-derived MSCs being considered safer than those derived from adipose tissue or perinatal tissue 1
- The degree of cell expansion and the use of non-immunogenic supplements 1
- The use of anticoagulation treatment and hemocompatibility screening to minimize the risk of adverse events 1
- The reporting of anti-coagulant use within clinical trial protocols 1
From the Research
Definition and Properties of Mesenchymal Stem Cells
- Mesenchymal stem cells (MSCs) are adult stem cells that can be isolated from most adult tissues, including bone marrow, adipose, liver, amniotic fluid, lung, skeletal muscle, and kidney 2.
- MSCs possess immunomodulatory properties, including suppression of T cell proliferation, influencing dendritic cell maturation and function, suppression of B cell proliferation and terminal differentiation, and immune modulation of other immune cells such as NK cells and macrophages 2, 3.
Therapeutic Applications of Mesenchymal Stem Cells
- MSCs are being tested in four main areas: tissue regeneration for cartilage, bone, muscle, tendon, and neuronal cells; as cell vehicles for gene therapy; enhancement of hematopoietic stem cell engraftment; and treatment of immune diseases such as graft-versus-host disease, rheumatoid arthritis, experimental autoimmune encephalomyelitis, sepsis, acute pancreatitis, and multiple sclerosis 2.
- MSCs have been shown to be effective in the treatment of various diseases, including dermatological, musculoskeletal, neurological, cardiovascular, respiratory, renal, gastroenterological, and urological conditions 4.
Mesenchymal Stem Cells and Graft-Versus-Host Disease
- MSCs have emerged as a therapeutic approach for the treatment and prevention of graft-versus-host disease (GVHD) due to their unique properties of tissue repair and major histocompatibility complex-unmatched immunosuppression 5.
- The use of MSCs to treat or prevent GVHD has shown promise in clinical trials, but further studies are needed to fully understand their effects and to identify the optimal therapeutic schedule 6.