**Author details**

**6. Conclusion**

18 Regenerative Medicine and Tissue Engineering

tency genes.

cells in CF lungs.

transplantation should be evaluated in detail [215].

Placenta-derived stem cells are endowed with interesting features that are important for choosing them as a source for approaches aimed to regenerative medicine: immune-privileged status, secretion of biomolecules with anti-scarring and anti-inflammatory properties, and, least but not last, no ethical concerns. Although the AM and AM-derived stem cells have been used in the clinics for over one hundred years, their employment in lung and liver diseases is coming on the stage only in the last few years. Placenta-derived stem cells have been recently more thoroughly characterized for their phenotype, multipotency and expression of pluripo‐

In CF, lung disease has been the target first of gene therapy approaches brought to the clinical stage [206, 207], hesitated in a slow progression due to limited efficiency of gene transfer vectors and pathophysiological barriers, and then of stem cell-based experimental treatments in mice [208]. Despite a very low level of engraftment of donor HSPC into the nose and the gut, significant CFTR mRNA expression and a measurable level of correction of the electro‐ physiological defect were observed after transplantation of wild-type marrow cells into CF mice [209]. It is uncertain whether this effect is due to the presence of CFTR-expressing epithelial cells derived from donor cells or to the paracrine effects of transplanted cells. Other sources, such as umbilical cord blood, embryonic stem cells, and induced pluripotent stem cells are being evaluated [210, 211]. Recent *in vitro* data on the acquisition of CFTR expression by hAMSC indicate placenta-derived stem cells as a possible source for treating the early phases of CF lung disease. Anyhow, caution should be taken when stem cell-based therapies are proposed for an inflammatory disease like that of CF lung, in view of the fact that these cells could be immunosuppressive and/or contribute to the inflammatory process. There is no available information concerning the immunomodulatory effects of placenta-derived stem

Liver fibrosis is a common outcome of a variety of chronic liver diseases following different insults, including the biliary disorder occurring in CF. Orthotopic liver transplantation remains the only viable therapeutic option to treat CF patients with hepatic cirrhosis, and hepatocyte transplantation has never been attempted in this disease. The use of progenitor cell transplan‐ tation is emerging as a potential alternative, and several potential sources have been identified for the isolation of these cells [212]. For the treatment of liver cirrhosis, this approach has been performed mainly with BM-derived MSC [213, 214]. Given the drawbacks related to the use of BM-derived MSC (limited frequency, invasive procedure, age and disease state affecting the collection of healthy autologous BM), placenta-derived stem cells could represent a prime candidate for the treatment of liver fibrosis, since they are immunotolerated, can be isolated and produced at high yield, and do not provoke ethical debate. AM and AM-derived stem cells have been demonstrated to halt the progression of liver fibrosis and its evolution towards cirrhosis, but the long-term safety and therapeutic efficacy are not known yet, which warrant further studies. Moreover, optimal therapeutic regimens for clinical application of placentaderived stem cells, such as optimal doses, transplantation route and interval period for Annalucia Carbone1,2\*, Stefano Castellani2 , Valentina Paracchini1 , Sante Di Gioia2 , Carla Colombo1 and Massimo Conese2

\*Address all correspondence to: annalucia.carbone@gmail.com

1 Fondazione IRCCS Ca' GrandaOspedale Maggiore Policlinico, Cystic Fibrosis Center, Milan, Italy

2 Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
