Strategies to improve regenerative potential of mesenchymal stem cells

Abstract

In the last few decades, stem cell-based therapies have gained attention worldwide for various diseases and disorders. Adult stem cells, particularly mesenchymal stem cells (MSCs), are preferred due to their significant regenerative potential in cellular therapies and are currently involved in hundreds of clinical trials. Although MSCs have high self-renewal as well as differentiation potential, such abilities are compromised with "advanced age" and "disease status" of the donor. Similarly, cell-based therapies require high cell number for clinical applications that often require in vitro expansion of cells. It is pertinent to note that aged individuals are the main segment of population for stem cell-based therapies, however; autologous use of stem cells for such patients (aged and diseased) does not seem to give optimal results due to their compromised potential. In vitro expansion to obtain large numbers of cells also negatively affects the regenerative potential of MSCs. It is therefore essential to improve the regenerative potential of stem cells compromised due to "in vitro expansion", "donor age" and "donor disease status" for their successful autologous use. The current review has been organized to address the age and disease depleted function of resident adult stem cells, and the strategies to improve their potential. To combat the problem of decline in the regenerative potential of cells, this review focuses on the strategies that manipulate the cell environment such as hypoxia, heat shock, caloric restriction and preconditioning with different factors.

Keywords: Caloric restriction; Growth factors; Heat shock; Hypoxia; Stem cell aging.

Figure 1

Increased donor age, disease conditions and in vitro expansion of cells reduce stem cell potential, making the cells less suitable for cell-based therapies. Stem cell function can be enhanced using strategies such as hypoxia, heat shock, caloric restriction and growth factor preconditioning. These strategies positively affect proliferation, migration, paracrine activity and differentiation potential of cells, and reduce senescence and apoptosis. Such pretreatment of cells makes the cells more suitable for cell based regenerative therapies.

Figure 2

Challenges and limitations in using preconditioning strategies such as hypoxia, heat shock, caloric restriction and growth factor & cytokine. Certain challenges are common for all these preconditioning strategies. Selection of correct strategy for correct duration for preconditioning of mesenchymal stem cells (MSCs) isolated from different sources is important. Assessment of the use of more than one strategies at the same time, use of sophisticated equipment for application of these strategies and evaluation of tumorigenicity after use of preconditioned strategies is required. The figure insets further describe the specific challenges in using specific strategies for preconditioning of MSCs.