237The role of ECM deserves special attention since in one hand, the interactions of
the cells with the ECM provide essential mechanical signals and, on the other hand,
the ECM can concentrate important growth factors and cytokines by binding both
local and systemic biomolecules within the microenvironment (Bertin et al. 2016 ).
Only recently, tissue bioengineering using decellularization process described
that fetal tissues possess more coiled fibers and fibronectin than adult bioscaffolds
(Silva et al. 2016 ), which can increase the possibilities of applications in regenera-
tive medicine. For this, a concomitant effort have been done to in one hand study the
diversity of SC-derived from embryonic and fetal membranes and in other hand
describe the diversity of ECM molecules in these tissues and understand their func-
tions for cell proliferation, migration and differentiation (Favaron et al. submitted).
Considering the importance of the microenvironment for SC proliferation and
differentiation and the diversity of embryonic and fetal membrane-derived SC, this
chapter will addressed advances in the isolation, phenotyping, characteristics of the
microenvironment, and applications of yolk sac and amniotic membrane-derived
SC for human and veterinary regenerative medicine.
12.2 Yolk Sac Membrane and Derived Stem Cells
The yolk sac displays a remarkable diversity of developmental, structural and func-
tional characteristics, mainly because this is an unique extraembryonic membrane
that occurs in all vertebrates (Mossman 1987 ). In mammals, the yolk sac precedes
and supports the chorioallantoic placentation during early stages of pregnancy
(Sheng and Foley 2012 ) and it is responsible for maternal-fetal exchange (Favaron
et al. 2012 ). For this, special attention has been drawn to this fetal membrane, since
it maintains essential functions during early stages of gestation, including the hema-
topoiesis and development of the vascular system, nutrient transfer, migration of
primordial germinative cells, and organogenesis (such as the development of the
primitive intestine) (Mançanares et al. 2013 ; Hyttel et al. 2010 ; Jafredo et al. 2005 ;
Nakagawa et al. 2000 ; Auerbach et al. 1996 ).
Due to the primary hematopoiesis function, so far, much data on cell differentia-
tion from yolk sac tissues are available for hematopoietic SC from mice and humans
(Jafredo et al. 2005 ; Auerbach et al. 1996 , 1998 ; Yoder et al. 1997 ; Huang and
Auerbach 1993 ; Globerson et al. 1987 ). In contrast to what was expected the precur-
sor cells derived from pluripotent SC isolated from yolk sac tissues are not fully
totipotent, but were able to differentiate into lymphocytes, granulocytes, mono-
cytes, erythrocytes, and megakaryocytes (Zhang et al. 2003 ; Palis and Yoder 2001 ;
Ikuta and Weissman 1992 ). Despite this, the extraembryonic hematopoietic SC
derived from the yolk sac are consider a valuable source of SC to support existing
transplantation therapies in clinical regenerative medicine (Sugiyama et al. 2011 ;
Wilpshaar et al. 2002 ). In addition, the understand of both biology and
microenvironment of the hematopoietic SC in the yolk sac membrane in different
phases of the gestation is crucial to improve their use on cell therapies.
12 Fetal Membranes-Derived Stem Cells Microenvironment