State-of-the-Art on Basic and Applied Stem Cell Therapy;Stem Cell Research Italy–International Society for Cellular Therapy Europe,Joint Meeting,Montesilvano (PE)–Italy,June 10–12,2011

T he congress organizers, prof. Assunta Pandolfi (Aging Research Center, Ce.S.I., “Gabriele d'Annunzio” University Foundation, and Department of Biochemical Sciences, University of “G. d'Annunzio,” Chieti-Pescara, Italy); the president of SCR Italy, Prof. Umberto Galderisi (Second University of Naples, Italy and Temple University, PA); and the president of ISCT Europe, Dr. Francesco Lanza (Cremona Hospital, Italy) highlighted the need to bring together basic and applied research with the newest insights in stem cell therapy. Indeed, before being suitable for clinical applications, stem cell biology requires to be investigated further and in greater detail to better clarify both stem cell action mechanisms and potential clinical applications.

The presentations covered a spectrum of stem cell subtypes with their newest basic and applied research. Human mesenchymal stem cells (hMSCs), amniotic fluid–derived (AFS) stem cells, neural stem and progenitor cells (NPCs), adipose-derived MSCs (ASCs), embryonic stem cells (ESCs), and adult renal progenitor cells (ARPCs) were the subjects of main reports. Basic stem cell research sessions concerned: the role of several transcription factors in hMSC differentiation and their important potential implications for bone tissue engineering applications; the development of a specific marker to successfully isolate ESC-derived pacemaker myocytes; novel findings on lipid metabolic pathway in human glioblastoma stem cells; and a validation process for the isolation, expansion, and quality testing of hMSCs from bone marrow, using good manufacturing practice (GMP)-compliant reagents. Preclinical stem cell research sessions focused on the use of AFS cells in a model of necrotizing enterocolitis and the role of NPCs in brain regeneration, where they can promote tissue repair, not only via cell replacement, but also via their local contribution to changes in the diseased tissue milieu, opening the way for experimental stem cell–based transplantation systems for central nervous system (CNS) repair. In this session, a remarkable topic was covered by Prof. Stefano Pluchino (University of Cambridge, United Kingdom). He gave a detailed explanation of the role of secreted noncoding RNAs and therapeutic neural stem cell plasticity. This remarkable therapeutic plasticity of neural stem/precursor cells is derived from their ability to communicate between adjacent cells horizontally. Interestingly, the first proposed mechanism of stem cell action, the replacement of lost or damaged cells, has been replaced by findings suggesting that the CNS is in fact sustained by other supportive mechanisms. A new mechanism that is gaining attention is the trafficking of membrane vesicles between adjacent neural precursor cells. Further studies are needed to better unravel this form of communication, with a role for noncoding RNAs a seemingly strong candidate. The discovery of the biological mechanisms underlying this kind of cell communication will hopefully translate into innovative clinical therapies for neurodegenerative diseases.

Another main research study investigated the pivotal role of the MeCP2-mediated senescence in neural cell fate and neuronal maintenance. The optimization of cytokine-induced killer cell expansion in clinical-grade cultures was also discussed. Several interesting talks were focused on the application of stem cells in various disease models. Indeed, neural differentiation process in MSCs obtained from a Rett syndrome patient and from healthy donors was evaluated, as well as the effect of ASCs in several experimental models of neurological diseases with different pathogeneses. Potential therapeutic application of hMSCs in neuropathic pain management and the influence of ARPCs on the regenerative process of cisplatin-injured renal proximal tubular epithelial cells were also discussed. Another promising frontier in stem cell application could be to develop novel combined gene- and neural stem cell–based approaches to correct metabolic defects and to restore tissue damage in leukodystrophies. Challenging research on the novel therapeutic tools to treat cancer concerns the use of ASCs modified to produce antitumoral molecules.

In the session concerning new perspectives for applied stem cell therapy, the main aims of the talks were to translate our understanding of basic stem cell functions into innovative clinical therapies for diseases. Tissue engineering approaches using advanced biomaterials represent the future of regenerative medicine. Excellent talks were focused on the therapeutics of biomaterials in cardiac tissue engineering, and on the development of polymer-based strategies to deliver stem cells to the damaged cardiac site. Indeed, Prof. Valentina Di Felice (University of Palermo, Italy) gave an excellent talk on the therapeutics of biomaterials in cardiac tissue engineering. Optimizing not only the best delivery route but also the best time for cell injection into the myocardium is a challenging research area. One possibility could be offered by the 3-dimensional scaffolds. They are able to support a limited number of stem cells in their undifferentiated state. Unfortunately, many biomaterials appear likely to cause a foreign body reaction. The Di Felice research group has recently demonstrated that c-Kit positive cardiac progenitor cells are able to organize themselves into a tissue-like cell mass in collagen I 3-dimensional cultures. These cells are able to create an organized elementary myocardium inside an open-pore polylactic acid scaffold, where they can produce a high concentration of natural extracellular matrices and are also able to create vessels. The results presented showed that the cells implanted within scaffolds were rapidly degraded by the foreign body reaction, indicating that scaffolds are useful devices to deliver cardiac stem cells in the site of implantation, but more research is needed to find nonreactive biomaterials.

Stem cell therapy represents the great promise for the future of molecular and regenerative medicine. Preliminary clinical evidences suggest that stem cell therapy could provide good results. However, further deep and exhaustive investigations on stem cell biology will be needed before stem cell therapies can become a successful reality. Applied stem cell research together with tissue engineering offers a promising new approach to handling several diseases. Future researches will drive their goal toward this direction.