Review: Preclinical studies on placenta-derived cells and amniotic membrane: An update O. Parolini * , M. Caruso Centro di Ricerca E. Menni, Fondazione Poliambulanza-Istituto Ospedaliero, Via Bissolati 57, I-25124 Brescia, Italy article info Article history: Accepted 13 December 2010 Keywords: Placenta Amniotic membrane Placenta-derived cells abstract Recent years have seen considerable advances in our knowledge of the biology and properties of stem/ progenitor cells isolated from placental tissues. This has encouraged researchers to address the potential effects of these cells in animal models of different diseases, resulting in increasing expectations regarding their possible utility for cell-based therapeutic applications. This rapidly evolving research field is also enriched by studies aimed at expanding the use of the whole amniotic membrane (AM), a well-known surgical material, for pathological conditions other than those tested so far and for which clinical applications already exist. In this review, we provide an update on studies that have been performed with placenta-derived cells and fragments of the entire AM to validate their potential clinical applications in a variety of diseases, in particular those associated with degenerative processes induced by inflammatory and fibrotic mecha- nisms. We also offer, as far as possible, insight into the interpretation and suggested mechanisms to explain the most important outcomes achieved to date. Ó 2011 Published by IFPA and Elsevier Ltd. 1. Introduction The placenta is generally recognized for important functions such as nutrition, respiration and excretion as well as maintenance of fetomaternal tolerance. The components of this organ include the fetal membranes, umbilical cord and trophoblast. In recent years, besides the use of fragments of the entire amniotic membrane (AM) as a surgical material [1,2], much attention has been given to the different cell types that can be isolated from the placenta. Progress in understanding the biology and properties of these cells has encour- aged researchers to explore their potential effects in animal models of different diseases, in the hope of future clinical applications [3,4]. 1.1. Placenta-derived cells Several researchers have reported the isolation and character- ization, from human and animal placentas, of cell populations with the properties of stem/progenitor cells [3]. Considering the current lack of standardization regarding the isolation and cultivation of placental cells applied in different laboratories and given that, in many cases, there is no precise description of the placental regions from which the cells are isolated, it is often quite difficult to compare results reported by different groups. This is further complicated by the fact that some groups work with freshly isolated cells, while others work with cultured and expanded cells, opening the possi- bility that the culture conditions themselves may give rise to selec- tion of different cell populations. This scenario is further confounded by the different developmental origins of cells isolated from human and non-human placentas. Indeed, it is important to bear in mind that, whilst the placentas of eutherian mammals share common physiological and functional features, there are remarkable differ- ences in terms of macroscopic and microscopic structure. Generally, classification of the placental types encountered in mammals is based on two main characteristics: i) the shape of the placenta and the distribution of contact sites between the fetal membranes and endometrium (diffuse, cotyledonary, zonary or discoid); ii) the number of tissue layers intervening between the maternal and fetal blood (epitheliochorial, endotheliochorial, and hemochorial). Moreover, differences exist between animals with a similar type of placentation (e.g. human and mouse) [5,6]. These differences should be kept in mind when selecting isolation protocols for placental cells, and especially when adapting protocols from one species to another, in order to ensure that cells are derived from the same anatomical region, thereby avoiding misinterpretations, as highlighted in some recent reports [6]. In this review, when discussing cells isolated from the human amniotic membrane, we will adopt the nomenclature of Parolini * Corresponding author. Tel.: þ39 0302455754; fax: þ39 0302455704. E-mail addresses: ornella.parolini@tin.it, parolini-ornella@poliambulanza.it (O. Parolini). Contents lists available at ScienceDirect Placenta journal homepage: www.elsevier.com/locate/placenta 0143-4004/$ e see front matter Ó 2011 Published by IFPA and Elsevier Ltd. doi:10.1016/j.placenta.2010.12.016 Placenta 32, Supplement B, Trophoblast Research, Vol. 25 (2011) S186eS195