Disclosure of potential conflicts of interest is found at the end of this article.

Bone marrow (BM) multipotent mesenchymal stromal cells (MSCs) present with multipotent differentiation potential and immunomodulatory properties. As an alternative to bone marrow, we have examined fetal membranes, amnion and chorion, of term human placenta as a potential source of multipotent MSCs. Here we show that amnion mesenchymal cells (AMCs) and chorion mesenchymal cells (CMCs), isolated by mechanical separation and subsequent enzymatic digestion, demonstrate plastic adherence and fibroblast-like morphology and are able to form colonies that could be expanded for at least 15 passages. By FACS analysis, AMCs and CMCs were shown to be phenotypically similar to BM-MSCs and, when cultured in differentiation media, they demonstrated high morphogenetic plasticity by differentiating into osteocytes, chondrocytes and adipocytes. In an attempt to isolate cells with MSC characteristics from human fetal membranes, AMCs and CMCs expressing CD271 were enriched by immunomagnetic isolation and were demonstrated to possess higher clonogenic and osteogenic differentiation potential than CD271-depleted fractions. Based on these findings, amnion and chorion can be considered as a novel and convenient source of adult MSCs.

Human amnion and chorion cells from term placenta can successfully engraft neonatal swine and rats. These results may be explained by the peculiar immunologic characteristics and mesenchymal stem cell-like phenotype of these cells. These findings suggest that amnion and chorion cells may represent an advantageous source of progenitor cells with potential applications in a variety of cell therapy and transplantation procedures.

Human amniotic membranes and amniotic fluid have attracted increasing attention in recent years as a possible reserve of stem cells that may be useful for clinical application in regenerative medicine. Many studies have been conducted to date in terms of the differentiation potential of these cells, with several reports demonstrating that cells from both the amniotic fluid and membrane display high plasticity. In addition, cells from the amniotic membrane have also been shown to display immunomodulatory characteristics both in vivo and in vitro, which could make them useful in an allotransplantation setting. Here, we provide an overview comparing the latest findings regarding the stem characteristics of cells from both the amniotic membrane and amniotic fluid, as well as on the potential utility of these cells for future clinical application in regenerative medicine.

Among the many cell types which may prove useful to regenerative medicine, mounting evidence suggests that human term placenta-derived cells will join the list of significant contributors. In making new cell therapy-based strategies a clinical reality, it is fundamental that no a priori claims are made regarding which cell source is preferable for a particular therapeutic application. Rather, ongoing comparisons of the potentiality and characteristics of cells from different sources should be made to promote constant improvement in cell therapies, and such comparisons will likely show that individually-tailored cells can address disease-specific clinical needs. The principle underlying such an approach is resistance to the notion that comprehensive characterization of any cell type has been achieved, neither in terms of phenotype nor risks-to-benefits ratio. Tailoring cell therapy approaches to specific conditions also requires an understanding of basic disease mechanisms and close collaboration between translational researchers and clinicians, to identify current needs and shortcomings in existing treatments. To this end, the international workshop entitled "Placenta-derived stem cells for treatment of inflammatory diseases: moving toward clinical application" was held in Brescia, Italy, in March 2009, and aimed to harness an understanding of basic inflammatory mechanisms inherent in human diseases with updated findings regarding biological and therapeutic properties of human placenta-derived cells, with particular emphasis on their potential for treating inflammatory diseases. Finally, steps required to allow their future clinical application according to regulatory aspects including good manufacturing practice (GMP) were also considered. In September, 2009, the International Placenta Stem Cell Society (IPLASS) was founded to help strengthen the research network in this field.

An urgent current need in regenerative medicine is that of identifying a plentiful, safe and ethically acceptable stem cell source for the development of therapeutic strategies to restore functionality in damaged or diseased organs and tissues. In this context, human term placenta represents a prime candidate, as it is available in nearly unlimited supply, is ethically problem-free and easily procured. Placental cells display differentiation capacity toward all three germ layers, while also displaying immunomodulatory effects, therefore supporting the possibility that they could be applied in an allogeneic transplantation setting. Although promising data have been reported to date, further study is required to fully characterize the differentiation potential of placenta-derived cells and to identify their possible clinical applications. Here, we provide a snapshot of current knowledge regarding the potential of cells from the amniotic membrane of human term placenta to address current shortcomings in the field of regenerative medicine.

Regenerative medicine is a new field primarily based on the concept of transplanting exogenous or stimulating endogenous stem cells to generate biological substitutes and improve tissue functions. Recently, amnion-derived cells have been reported to have multipotent differentiation ability, and these cells have attracted attention as a novel cell source for cell transplantation therapy. Cells isolated from amniotic membrane can differentiate into all three germ layers, have low immunogenicity and anti-inflammatory function, and do not require the destruction of human embryos for their isolation, thus circumventing the ethical debate commonly associated with the use of human embryonic stem cells. Accumulating evidence now suggests that the amnion, which had been discarded after parturition, is a highly potent transplant material in the field of regenerative medicine. In this report, we review the current progress on the characterization of MSCs derived from the amnion as a remarkable transplantable cell population with therapeutic potential for multiple CNS disorders, especially stroke.

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