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12.1 Introduction
Regenerative medicine is defined as a branch of translational research that congre-
gates important areas related to tissue engineering and cellular therapy (Mason and
Dunnill 2008 ). When combined they provide promising alternatives to overcome
several human and veterinary medical problems related to the replacement of tis-
sues and organs that have been damage by diseases, trauma and congenital issues,
which in the present scenario especially for humans, can not be solved by tissues
and organs donation and transplantation (Mahla 2016 ).
In the last 20 years, cellular therapy has grown a lot and several different stem
cells (SC) lineages from different organs and species have been established and
characterized (Fernandes et al. 2012 ; Avasthi et al. 2008 ). SC are present in all
organisms during the life and are defined according to the ability of keeping the
undifferentiated state along the life (self-renewal capacity) or undergoing differen-
tiation on specialized cell types, after specific stimuli, or using specific cell culture
media associated with growth factors in vitro (Bertin et al. 2016 ).
Nevertheless, the obtaining and use of SC, especially those obtained from embry-
onic tissues that show higher capacity of proliferation and differentiation (Zare et al.
2014 ) are limited by political, ethical, social, and legal regulations (Gupta 2009 ). In
order to overcome these issues, the fetal membrane tissues, an abundant, ethically
acceptable and readily accessible source of SC have been investigated in the recent
years (Lobo et al. 2016 ; Favaron et al. 2014 , 2015 ; Mançanares et al. 2015 ;
Fernandes et al. 2012 ). Compared to SC derived from their adult counterparts, the
fetal membrane SC have higher proliferation abilities, greater differentiation poten-
tial being generally defined as multipotent (Bertin et al. 2016 ; Fratini et al. 2016 ),
do not cause immunological troubles (Bobis et al. 2006 ), and they are consider a
safe cell lineage for in vivo applications (Vidane et al. 2014 ).
Recently, the SC and their effects have not been studied alone, but considering
their relationship with the microenvironment or the niche associated to these cells.
The niche is responsible to define the morpho-physiological and biochemical char-
acteristics of the microenvironment where quiescent SC are located before specific
signals activate the process of cell differentiation. In particular, this dynamic com-
partment performs mainly three functions: (1) controls process related to SC prolif-
eration, (2) determines the fate of SC daughters and (3) protects SC from exhaustion
or death (Bertin et al. 2016 ). In this regard, there is a strict relationship between the
SC and the niche, that permits to the SC by cellular mechano-transducers sense
changes in the matrix elasticity, resulting in morphological and differentiation
changes of the SC (Engler et al. 2006 ). It is known that there are common elements
constituting the SC microenvironment or their niche: (1) stromal cells that support
SC interacting with each other via cell surface receptors and soluble factors, (2) the
vasculature and nervous system that drag systemic and physiological inputs and (3)
extracellular matrix (ECM) proteins, such as: fibronectin, laminin, elastin, and the
collagen system (Arenas and Zurbarán 2002 ), which all together supply structural
organization, mechanical signals to the niche, cell migration, proliferation and
differentiation (Bertin et al. 2016 ; Nogami et al. 2016 ; Choi et al. 2013 ; Yamazaki
et al. 2011 ; Brown et al. 2010 ; Engler et al. 2006 ).
P.O. Favaron and M.A. Miglino