Strategies to retain properties of bone marrow–derived mesenchymal stem cells ex vivo

Abstract

Mesenchymal stem cells (MSCs) have been extensively used for cell therapies and tissue engineering. The current MSC strategy requires a large quantity of cells for such applications, which can be achieved through cell expansion in culture. In the body, stem cell fate is largely determined by their microenvironment, known as the niche. The complex and dynamic stem cell niche provides physical, mechanical, and chemical cues to collaboratively regulate cell activities. It remains a great challenge to maintain the properties of MSCs in culture. Constructing a microenvironment as an engineered stem cell niche in culture to maintain MSC phenotypes, properties, and functions is a viable strategy to address the issue. Here, we review the current understanding of MSC behavior in the bone marrow niche, describe different strategies to engineer an in vitro microenvironment for maintaining MSC properties and functions, and discuss previous findings on environmental factors critical to the modulation of MSC activities in engineered microenvironments.

Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies

“…Many studies have demonstrated the effects of MSC priming with pro-inflammatory cytokines or growth factors. This strategy aims to improve the immunosuppressive function and to increase their secretion of anti-inflammatory and immunomodulatory factors [ 11 , 14 – 16 ] (Table 1 , Fig. 2 ).…”

“…ECM is an important component of the bone marrow niche, acting as a physical support for cell adhesion in a 3D environment. In order to mimic the MSC niche, researchers have explored the use of different 3D biomaterials for cell culture [ 11 ]. In fact, MSC applications in tissue engineering are largely associated with the development of biomaterials, which can direct MSC fate towards the desired phenotype and also provide a microenvironment that allows for structural and biochemical cellular support, thereby enhancing tissue healing [ 105 ].…”

“…MSC properties are influenced by in vivo and in vitro biological, biochemical, and biophysical factors, which tightly regulate MSC functions and survival [ 11 ] through reciprocal interactions between the cells, extracellular matrix (ECM), and soluble bioactive factors. MSC interact with surrounding tissues and cells in a three-dimensional space, regulating the ECM, therefore promoting angiogenesis, producing anti-inflammatory molecules, preventing cell death (anti-apoptotic effects), and modulating the immune system [ 12 ].…”

“…To date, several studies have demonstrated that the modulation of biological, biochemical, and/or biophysical factors can influence MSC fate, lineage-specific differentiation, and functions and also enhance their therapeutic potential [ 12 , 13 ]. One of the first reported approaches was cell priming (also referred to as licensing or preconditioning) with pro-inflammatory mediators [ 11 , 14 – 17 ]. Cell priming consists of preparing cells for some specific function or lineage-specific differentiation, which involves cell activation, molecular signaling, genetic or epigenetic modifications, and morphology/phenotype changes.…”

Role of Mesenchymal Multipotent Stromal Cells in Remodeling of Bone Defects

“…В осуществлении межклеточных кон-тактов участвуют такие адгезионные молекулы MCК, как CD274 (PDL 1) и galectin-1, которые индуцируются IFNγ и осуществляют иммуно-модулирующее действие МСК [47]. МСК ре-гулируют как адаптивный, так и врожденный иммунитет -посредством угнетения активации и пролиферации Т-и В-лимфоцитов, подавления созревания дендритных клеток, ингибирования пролиферации и цитотоксичности NK-клеток, а также способствуя образованию регуляторных Т-клеток [59]. МСК также препятствуют обра-зованию плазматических клеток и индуцируют IL-10 + и CD19 + CD38 high CD24 high B-клетки, кото-рые рассматриваются как регуляторные В-клетки (Breg).…”