Abstract
Tissue engineering of replacement tissues and organs manufactured with stem cells and biocompatible scaffolds has become a today’s reality. Bone marrow harbours the two types of adult stem cells—haematopoietic stem cells (HSCs) and multipotential stromal cells (MSCs). Up to date, clinical use of MSCs mostly relies on culture expansion; however, current MSC culture-expansion protocols, although clinically permittable, do not guarantee the preservation of native MSC characteristics and yield cellular products of variable quality and potency, which could be accountable for varied treatment outcomes. As a consequence, new technologies have now emerged that are based on uncultured MSCs, of various degrees of purity, in clinical settings. This chapter will provide an overview on the current state of the art in the field of uncultured MSCs as cell therapy. We will discuss highly pertinent safety issues such as purity and the role of contaminating immune and non-immune cells. Parallels will be drawn with similar treatments with cultured MSCs and uncultured HSCs. Other currently unresolved issues, such as MSC dose, route of delivery and donor-to-donor variability, for both uncultured and culture-expanded MSCs, will be discussed. Finally, we will briefly elaborate on acellular approach such as delivering MSC-derived exosomes or inducing endogenous MSC homing with the use of bioactive molecules to direct resident MSC migration to target areas in vivo. This combined knowledge should provide the platform for developing novel, safe and cost-effective MSC therapies with improved efficacy based on non-expanded MSCs and be also relevant for using other types of adult stem cells as cell therapy.