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

Abstract

Multipotent mesenchymal stromal cells (MSC) have been widely explored for cell-based therapy of immune-mediated, inflammatory, and degenerative diseases, due to their immunosuppressive, immunomodulatory, and regenerative potentials. Preclinical studies and clinical trials have demonstrated promising therapeutic results although these have been somewhat limited. Aspects such as low in vivo MSC survival in inhospitable disease microenvironments, requirements for ex vivo cell overexpansion prior to infusions, intrinsic differences between MSC and different sources and donors, variability of culturing protocols, and potency assays to evaluate MSC products have been described as limitations in the field. In recent years, priming approaches to empower MSC have been investigated, thereby generating cellular products with improved potential for different clinical applications. Herein, we review the current priming approaches that aim to increase MSC therapeutic efficacy. Priming with cytokines and growth factors, hypoxia, pharmacological drugs, biomaterials, and different culture conditions, as well as other diverse molecules, are revised from current and future perspectives.

Keywords: Biomaterials; Cell therapy; Culture conditions; Mesenchymal stromal cells; Pharmaceutical drugs; Priming; Pro-inflammatory cytokines.

Fig. 1

Overview of the production of primed MSC for the treatment of different disease types. Six steps for primed MSC production are indicated: tissue source selection, MSC isolation, MSC priming (the four main classes of priming approaches currently available are represented), MSC expansion, MSC product formulation, MSC administration, and application in different disease types. The rationale is to use different MSC sources/priming approaches for different clinical applications

Fig. 2

Schematic representation of the main priming approaches to improve MSC therapeutic efficacy. Priming with a cytokines or growth factors, b pharmacological or chemical agents, c hypoxia, d 3D culture conditions. Priming factors/agents and their respectively triggered mechanisms are linked by arrows and boxes of the same color. Released soluble factors are represented in continuous-line boxes, while other upregulated molecules (such as transcription factors, metalloproteinases, chemokine receptors, and enzymes) are represented in dashed-line boxes. The general priming effects on MSC (immunomodulatory, migratory, regenerative, immunosuppressive and migration, angiogenic, survival and engraftment, anti-apoptotic, increase stemness) triggered by the priming factor/agent are indicated in yellow boxes at the bottom of each figure