Mesenchymal Stem Cells in Homeostasis and Systemic Diseases: Hypothesis, Evidences, and Therapeutic Opportunities

Abstract

Mesenchymal stem cells (MSCs) are present in all organs and tissues, playing a well-known function in tissue regeneration. However, there is also evidence indicating a broader role of MSCs in tissue homeostasis. In vivo studies have shown MSC paracrine mechanisms displaying proliferative, immunoregulatory, anti-oxidative, or angiogenic activity. In addition, recent studies also demonstrate that depletion and/or dysfunction of MSCs are associated with several systemic diseases, such as lupus, diabetes, psoriasis, and rheumatoid arthritis, as well as with aging and frailty syndrome. In this review, we hypothesize about the role of MSCs as keepers of tissue homeostasis as well as modulators in a variety of inflammatory and degenerative systemic diseases. This scenario opens the possibility for the use of secretome-derived products from MSCs as new therapeutic agents in order to restore tissue homeostasis, instead of the classical paradigm “one disease, one drug”.

Unraveling the therapeutic effects of mesenchymal stem cells in asthma

“…Several experiments revealed that MSCs exhibited a different restorative capacity based on isolation from various tissues. Also, the MSC subtype possesses a different multipotential capacity [59]. Bone marrow is a primary and well-known source for the isolation of MSCs.…”

The Coronavirus Pandemic (SARS-CoV-2): New Problems Demand New Solutions, the Alternative of Mesenchymal (Stem) Stromal Cells

“…Stem cells, although in minimal quantities, are present in many tissues of the body including the lungs, and participate and control tissue renewal. Furthermore, there is a subtype of stem cells, relatively unknown until recently, called mesenchymal (stem) stromal cells (MSC), which are active sentinels and regulators in tissue homeostasis (Vizoso et al, 2019). In fact, it has been proposed that in many degenerative, autoimmune diseases (such as lupus, rheumatoid arthritis, psoriasis, etc.…”

“…Due to the moderate efficacy of MSC applications in the first clinical trials, research was carried out toward cellular modifications of MSC in order to improve their biological effect, such as genetic modifications, MSC preconditioning, pharmacologic modulation, or the combined application of MSC together with pharmacologic therapies (Vizoso et al, 2019). However, there is a growing trend in the scientific community to recognize that the beneficial therapeutic effect of MSC relies on the cocktail of substances that clump together under the generic term of secretome (growth factors, cytokines, or extracellular vesicles).…”

“…Exosome production and storage are easier than production of parent cells. Preclinical studies demonstrated the safety of MSC-derived exosomes, with mass scalable production possible at clinically relevant doses (Vizoso et al, 2019).…”

A comparative study on normal and obese mice indicates that the secretome of mesenchymal stromal cells is influenced by tissue environment and physiopathological conditions

“…Pathological conditions may alter the microenvironment surrounding MSCs a d impair their functions. Some findings have demonstrated that MSC dysfunctions are associated with several diseases, including diabetes, lupus, psoriasis, rheumatoid arthritis, and metabolic syndrome [8,9].…”