Novel insights for improving the therapeutic safety and efficiency of mesenchymal stromal cells

Abstract

Mesenchymal stromal cells (MSCs) have attracted great interest in the field of regenerative medicine. They can home to damaged tissue, where they can exert pro-regenerative and anti-inflammatory properties. These therapeutic effects involve the secretion of growth factors, cytokines, and chemokines. Moreover, the functions of MSCs could be mediated by extracellular vesicles (EVs) that shuttle various signaling messengers. Although preclinical studies and clinical trials have demonstrated promising therapeutic results, the efficiency and the safety of MSCs need to be improved. After transplantation, MSCs face harsh environmental conditions, which likely dampen their therapeutic efficacy. A possible strategy aiming to improve the survival and therapeutic functions of MSCs needs to be developed. The preconditioning of MSCs ex vivo would strength their capacities by preparing them to survive and to better function in this hostile environment. In this review, we will discuss several preconditioning approaches that may improve the therapeutic capacity of MSCs. As stated above, EVs can recapitulate the beneficial effects of MSCs and may help avoid many risks associated with cell transplantation. As a result, this novel type of cell-free therapy may be safer and more efficient than the whole cell product. We will, therefore, also discuss current knowledge regarding the therapeutic properties of MSC-derived EVs.

Keywords: Cell-therapy; Efficiency; Extracellular vesicles; Mesenchymal stromal cells; Preconditioning; Safety.

Figure 1

A flow chart showing the use of the cell-free approach could enhance the safety of mesenchymal stromal cell-based therapy. MSC: Mesenchymal stromal cell; EVs: Extracellular vesicles.

Figure 2

Mesenchymal stromal cells as a promising therapeutic strategy with improved efficiency and safety. MSC: Mesenchymal stromal cell; EVs: Extracellular vesicles.

Figure 3

Strategies applied in the preconditioning of mesenchymal stromal cells. MSCs: Mesenchymal stromal cells.

Figure 4

The specific cytokine milieu is pivotal in determining the fate and behaviors of mesenchymal stromal cells. IFN-γ: Interferon-γ; IFN-β: Interferon-β; IDO: Indoleamine 2,3-dioxygenase.

Figure 5

Several environmental conditions modulate the pattern and function of toll-like receptors expressed by mesenchymal stromal cells. TLRs: Toll-like receptors.