Promises and Limitations in the Application of Cell Therapy for Tissue Regeneration

Stem cells research soared in recent years with the attempt to combine those cells from different sources with different matrices and apply them for regenerative medicine. There are a variety of potential types of cells that could be defined as stem cells. These include progenitor cells from adult tissues, cells from embryonic sources (ES), adult multipotent cells and those that were induced to acquire stem cells properties (IPS). New sophisticated matrices assembled from synthetic or bio-polymers were proposed as scaffolds for such cellular implants. Nevertheless, there is a major difficulty in translating knowledge in this field of cellular biology for tissue engineering. The cells induced to differentiate tend to age and lose their proliferative potential and it is difficult to introduce them into tissues so that they could replace cells in damaged tissues. Multipotent cells may not differentiate into the phenotype of interest. Moreover, some types may be teratogenic and induce malignant tumors. In direct implantation of matrix-dependent cells into tissues and organs, as well as through the circulation the vast fraction of the trypsinized matrix-dependent cells maybe lost in the procedure, not survive the implantation or may not integrate into the damaged tissues. Another difficulty is the limited ability of the cells to home towards the damaged tissues and integrate in it while they may just be trapped in highly capilarized organs such as the lungs and the kidneys. When the cells are implanted in-vitro within different scaffolds to produce 3D cellular structures, they may not survive implantation due to suffocation within the artificial matrix, which is not connected to the supply by vascularization network from the damaged tissues. Inflammatory processes that normally occur and is an integral component of the process of tissue repair may also result in the mass killing of cells, including the implanted stem cells. Therefore, in early controlled clinical studies the attempt of targeting isolated cells alone to repair tissues has yielded controversial results with poor cell survival and difficulty to show incorporation and integration of implanted cells into the target tissues. In view of the above difficulties new approaches are needed. Thus, currently, in spite of the great advances in the growing stem cells field and a wide selection of stem cells, solutions based on using the combination of progenitor cells and matrices for tissue regeneration have not yielded yet simple and straightforward methods to repair failing soft or hard tissues with cell based therapies.