Precise tissue bioengineering and niches of mesenchymal stem cells: Their size and hierarchy matter

Stem cell microterritories (niches), as a specialized part of the extracellular matrix (ECM), are considered an important target and tool for the development of new materials, medical implants, and devices. However, tissue bioengineering products that have stem cell niches of known size on the surface or in the bulk structure of artificial materials are practically unknown. This brief review attempts to draw attention to the problematic aspects of niches as specific parts of the ECM, such as their hierarchy and size for mesenchymal stromal/stem cells (MSCs). These parameters arise directly from numerous definitions of stem cell niches as specialized morphological microterritories found in various tissues. The authors of this review analyze the known information on the hierarchy of MSC microterritories by analogy with that of hematopoietic stem cells. Occasional reports on the size of artificial MSC niches compared to natural niche candidates are summarized. A consensus on a hierarchy and optimal range of niche sizes for MSCs and other stem cells is needed to accelerate the development of prototyping technologies and additive manufacturing in applications to precise tissue bioengineering and regenerative medicine.