In adults, tissue-specific stem cells are responsible for the replacement of differentiated cells within continuously regenerating tissues. In the past decade, they have attracted increasing attention and are now widely used in the field of regenerative medicine. Utilizing the self-renewal ability and differentiation attributes of stem cells, numerous tissues could be regenerated by a stem cell-based approach. For example, tissue engineering strategies based on stem cells exhibit promising potential for the regeneration of intervertebral discs, which was previously regarded as a non-repairing tissue. Therefore, it is important to regulate stem cells to realize their maximum regenerative efficiency.

Recent studies have shown the fate of stem cells may be significantly more dynamic than previously appreciated, including self-renewal, differentiation, death, migration, and adhesion. Numerous factors control and manipulate the cellular microenvironment to direct the fate of stem cells. These include physical, biochemical, and cell-cell interactions, as well as other factors in the microenvironment. It is essential to have a comprehensive understanding of the determinants of stem cell fate in the microenvironment so that we can better apply therapeutic strategies with precise control of specific microenvironmental characteristics to best regulate cells to promote tissue regeneration.

This Special Issue, therefore, invites contributions of both original research and review articles reporting recent efforts in the study and development of stem cell fate determinants in the microenvironment.

Potential topics include but are not limited to the following:

• Microenvironmental physics that regulate stem cell fate
• Microenvironmental biochemical factors that regulate stem cell fate
• Microenvironmental mechanics that regulate stem cell fate
• Microenvironmental intercellular crosstalk in the regulation of stem cell fate
• Microenvironmental immunomodulation for stem cell fate decisions
• Tissue microenvironment changes during aging and disease and their impact on the regulation of stem cell fate
• Bioengineering technology for remodeling the microenvironment with regard to regulating stem cell fate decisions