Therapeutic Mesenchymal Stem/Stromal Cells: Value, Challenges and Optimization

Abstract

Cellular therapy aims to replace damaged resident cells by restoring cellular and molecular environments suitable for tissue repair and regeneration. Among several candidates, mesenchymal stem/stromal cells (MSCs) represent a critical component of stromal niches known to be involved in tissue homeostasis. In vitro, MSCs appear as fibroblast-like plastic adherent cells regardless of the tissue source. The therapeutic value of MSCs is being explored in several conditions, including immunological, inflammatory and degenerative diseases, as well as cancer. An improved understanding of their origin and function would facilitate their clinical use. The stemness of MSCs is still debated and requires further study. Several terms have been used to designate MSCs, although consensual nomenclature has yet to be determined. The presence of distinct markers may facilitate the identification and isolation of specific subpopulations of MSCs. Regarding their therapeutic properties, the mechanisms underlying their immune and trophic effects imply the secretion of various mediators rather than direct cellular contact. These mediators can be packaged in extracellular vesicles, thus paving the way to exploit therapeutic cell-free products derived from MSCs. Of importance, the function of MSCs and their secretome are significantly sensitive to their environment. Several features, such as culture conditions, delivery method, therapeutic dose and the immunobiology of MSCs, may influence their clinical outcomes. In this review, we will summarize recent findings related to MSC properties. We will also discuss the main preclinical and clinical challenges that may influence the therapeutic value of MSCs and discuss some optimization strategies.

The potential use of mesenchymal stem cells and their exosomes in Parkinson’s disease treatment

“…For instance, less than 0.01% of the cells residing in bone marrow are MSCs, and this astonishingly low prevalence makes their isolation considerably difficult [ 118 ], particularly when one considers the fact that bone marrow aspiration is an invasive and painful procedure, and not all donors would opt to participate in such procedure. In this sense, adipose tissue might provide a better source for extraction of MSCs, as it is not as deeply located as the bone marrow, is more abundantly distributed throughout the body and can be accessed through less invasive methods [ 119 ].…”

Regenerative and Endoscopic Treatment of Complex Recurrent Fistula in Ano: When Technology Supports Clinical Treatment

“…The therapeutic efficacy of MSCs is due to the so-called secretome, which is a set of proteins secreted into the extracellular space, including exosomes and non-coding RNAs [19]. Exosomes are small vesicles that penetrate the cell membrane and release biochemical messages that have been shown to control immune response, inhibit inflammation, promote angiogenesis and cell proliferation, and induce repair by means of tissue regeneration instead of a scarring process [20].…”

Hexon modification of human adenovirus type 5 vectors enables efficient transduction of human multipotent mesenchymal stromal cells

“…MSCs have significant therapeutic potential in several medical areas, including in regenerative medicine (e.g., wound healing or bone repair), anti-inflammatory therapy (e.g., graft-versus-host disease or inflammatory disease of the CNS), or in cancer therapy. 1 , 2 , 3 , 4 , 5 They can be isolated from different tissues like bone marrow, 6 , 7 adipose tissue, and menstrual blood, possess unique characteristics such as secretion of immunomodulatory proteins, 8 , 9 can differentiate into a range of cell types, 10 and autonomously migrate toward inflammatory sites and tumor tissue. 11 , 12 , 13 To further improve the therapeutic potential of MSCs, some of the current efforts include attempts to genetically engineer MSCs, depending on the availability of suitable procedures for efficient nucleic acid delivery into MSCs.…”