Tissue injury occurring after ischemic, toxic or inflammatory insults leads to cell death and possibly to organ failure. The regeneration process taking place thereafter may result in the complete repair of the damaged tissue or, in partial/altered remodeling, in tissue fibrosis and scarring. This may depend on the intrinsic ability of different tissues to repair as well as on the entity and persistence of the injury. In this scenario, stem cell therapy can be viewed as a promising option in two different ways. The first is as a “support” mechanism, in which stem cells are exploited to promote complete tissue repair and avoid detrimental fibrosis. The other is the “replace” option, in which stem cells differentiate and substitute for damaged cells, providing an alternative to organ transplantation. This is of particular need in therapy for chronic organ failure.
In this issue of Organogenesis, authors with a recognized expertise in the field describe the possible approaches and current prospective for these two clinical needs.
Multipotent marrow stromal cells are the most established type of stem cells for organ repair and the most advanced in clinical development. Togel et al. review the possible applications of multipotent marrow stromal cells in the repair of kidney, heart and brain and discuss their potential detrimental effects. A complete view of the complex identity of these multipotent cells, identified as perivascular cells in different organs, is provided by Crisan et al. They propose a role for perivascular stem cells as originators of mesenchymal stem cells and consider their possible physiological role in tissue regeneration.
There is a general agreement that the mechanism of the beneficial effect of multipotent stromal cells in organ repair is due to a “support” mechanism rather than to their differentiation. In this light, Tetta et al. review the intriguing possibility of using bioproducts of stem cells, such as microvesicles, in place of the cells to support regeneration in damaged organs, such as the liver and kidney, and provide a novel, and possibly easier, approach to stem cell therapy.
Considering the option of “replacing” absent or dead cells, pluripotent stem cells of adult or embryonic origin may be suitable candidates by virtue of their possibility to differentiate in every organ-specific cell, therefore providing functional repair. Fagonee et al. present the role of germline-derived pluripotent stem cells in liver, heart and brain diseases and their future potentialities, and a similar approach is proposed by Harari-Steinberg and colleagues in a review focused on renal regeneration. The authors approach the need for generation of functional renal tissue by stem cells with a precise analysis of the possible options, from the use of embryonic stem cells to the generation of inducible pluripotent cells and, finally, to the interesting idea of reprogramming adult renal cells to obtain an inducible renal progenitor.
Finally, the review by Reule and Gupta touches on the most uncertain, but probably the most promising, challenge in organ regeneration, i.e., the use of resident stem cells. Identification, ex vivo administration or, possibly, pharmacological modulation of resident stem/progenitor cells could be the most feasible option for the repair of chronically damaged tissues with chronic loss of function, such as the kidney.
Benedetta Bussolati, M.D., Ph.D.
Department of Internal Medicine