Enhancing survival, engraftment, and osteogenic potential of mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are promising candidates for bone regeneration therapies due to their plasticity and easiness of sourcing. MSC-based treatments are generally considered a safe procedure, however, the long-term results obtained up to now are far from satisfactory. The main causes of these therapeutic limitations are inefficient homing, engraftment, and osteogenic differentiation. Many studies have proposed modifications to improve MSC engraftment and osteogenic differentiation of the transplanted cells. Several strategies are aimed to improve cell resistance to the hostile microenvironment found in the recipient tissue and increase cell survival after transplantation. These strategies could range from a simple modification of the culture conditions, known as cell-preconditioning, to the genetic modification of the cells to avoid cellular senescence. Many efforts have also been done in order to enhance the osteogenic potential of the transplanted cells and induce bone formation, mainly by the use of bioactive or biomimetic scaffolds, although alternative approaches will also be discussed. This review aims to summarize several of the most recent approaches, providing an up-to-date view of the main developments in MSC-based regenerative techniques.

Keywords: Mesenchymal stem cells, Bone regeneration, Hypoxia, Anoikis, Preconditioning, Bioactive scaffolds, Senescence, Engraftment, Homing, Osteogenesis

Core tip: Mesenchymal stem cells (MSCs) are important tools for a wide range of therapeutic applications, including the treatment of critical size fractures or bone defects. However, whereas early clinical studies showed great expectations, long-term benefits of MSC-based treatments are not entirely successful. Transplanted cells had to face a series of important challenges that greatly reduce their survival and engraftment, and thus, their capacity to regenerate the target tissue. Although there is solid data indicating that the paracrine actions exerted by MSCs are equally important in the outcome of the treatment, this review is based on the current strategies aimed to enhance tissue regeneration directly occurring from the engraftment and differentiation of the transplanted MSCs.