Stem cell plasticity: an overview.

The capacity of adult bone marrow cells to convert to cells of other tissues, referred to by many as stem cell plasticity, was the focus of the meeting in Providence entitled "Challenges in the Era of Stem Cell Plasticity". The meeting provided a showcase for the many impressive positive results on tissue restoration including the capacity of purified marrow stem cells to restore heart, skin, and liver function in impaired mice or humans. This area of research has become a center of controversy, although it is not clear why. Calls for clonality, robustness, and function have been shown to be erroneous or premature. A call for clonality (which has been shown nicely in one study) is meaningless on a predefined stem cell population which is intrinsically heterogeneous, as they all are. Robustness means nothing; it all depends on the details of the situation. Function on an organ level is, of course, the goal of many investigators and should not be raised as a limiting consideration. Lastly, fusion has been highlighted as undermining studies with adult stem cells. It, of course, does not. Fusion is simply a means to a final goal, which occurs in certain settings of marrow conversions (transdifferentiation) and not in others. We hypothesize that the conversion phenomena may, in fact, be due to one or several marrow stem cells with broad differentiation potential which can be expressed when the cell is placed in an environment with the appropriate inductive signals. Furthermore, initial events may be relatively rare and significant conversion numbers may be obtained with massive or ongoing selection. Fusion appears in an initial mechanism in some cases and not in others. Overall, the therapeutic potential of adult marrow stem cells is very intriguing, and successful use therapeutically will probably depend on definition of the most appropriate transplant model and tissue injury.