“Stem cell” – the term was first coined by Russian histologist Alexander Maksimov in 1908 to announce the existence of special cells capable of generating blood cells . Stem cells are at the heart of regenerative medicine and tissue engineering. Although there are several types of stem cells available depending on their origin and functionality; however, scientifically, they can be classified into four well-defined classes: (1) embryonic stem cells (ESC), (2) adult stem cells (ASC), for example, muscle satellite cells are muscle-specific adult stem cells, (3) induced pluripotent stem cells (iPSCs) and (4) pathological stem cells (PSCs), e.g. cancer stem cells (CSCs) [1]. Among these 4 types, ESCs and ASCs are true physiological stem cells, iPSCs are artificial stem cells, and PSCs are conditional stem cells. Among them, ESCs and iPSCs are considered true pluripotent stem cells, which have the capacity for unlimited self-renewal and differentiation into all types of specialized cells in the body. Therefore, these cells have been considered the most favorable cells for use in regenerative medicine and tissue engineering [2,3,4,5,6,7,8]. Stem cells need a special environment for their survival, maintenance and growth. Early in the establishment of stem cell culture methodologies, it was realized that they needed support from other cells, for example mouse embryonic fibroblasts (MEF). Co-culture methodology with gamma-irradiated MEF cells used as feeder cells and culture media enriched with fetal bovine serum (FBS) have been successfully used to establish in vitro stem cell culture [9,10]. . However, the use of second unrelated cells (although their growth is limited) is not suitable to use them for different purposes... middle of article ...... chimeric Fc protein introduced into the technology of stem cells about a decade ago, and over the years we and others have established several chimeric Fc proteins as significantly recognizable cellular biomaterials in stem cell technology. This work with a variety of chimeric Fc proteins ranging from ECM constitutive protein (e.g., ECad) to cytokine (e.g., HGF) has shown enormous potential to overcome major obstacles in stem cell technology, i.e. defined conditions for stem cell culture, selective differentiation of target lineages, convenient purification of desired cells, etc., for the application of stem cell technology targeting regenerative medicine. In this article, we will focus on chimeric proteins ECad-Fc and NCad-Fc as novel cell-recognizable biomaterials in stem cell technology for application in regenerative medicine..