Discovering adult stem cell expansion technologies

An over‐arching principle of our research is active integration of basic and applied investigations by design. Most recently, we have applied this principle to the challenge of enabling future adult stem cell‐based medical therapies. A major barrier to development of effective cellular therapies is difficulty producing functional tissue‐specific adult stem cells routinely and in large quantity. We addressed this problem by investigating molecular mechanisms in engineered cultured cell models that display the unique cell kinetics function of adult stem cells, asymmetric self‐renewal. Asymmetric self‐renewal, which functions to limit adult stem cell number in tissues, poses the major barrier to their expansion in culture. In the model cell studies, we discovered a p53‐dependent biochemical pathway that governs whether the self‐renewal kinetics of cells is asymmetric or symmetric. Whereas asymmetric self‐renewal maintains a constant adult stem cell number, symmetric self‐renewal leads to their rapid exponential expansion. Based on this discovery, we developed a new concept called “suppression of asymmetric cell kinetics” (SACK) for expansion of adult stem cells in culture. Recently, this concept was reduced to practice for expansion of cells with properties of adult stem cells from normal human liver. Based on the universality of asymmetric self‐renewal by adult stem cells, we anticipate that the SACK method will be effective for routine production of adult stem cells from diverse human tissues.