Appendix K. 
313 
Given the uncertainties involved in isolating and identifying 
particular adult stem cells, Moore and Quesenberry^° suggest that 
we consider an adult stem cell’s functional ability to be, at a 
minimum, taking on the morphology and cell markers of a 
differentiated tissue, supplemented by any further functional activity 
and interaction within a tissue. Certainly a physiological response 
by improvement of function in a damaged organ system is an 
indication of a functional response.^®’^° As will be discussed later, the 
function and therapeutic benefit may not necessarily require direct 
differentiation and integration of an adult stem cell into a desired 
tissue, but could be accomplished by stimulation of endogenous cells 
within the tissue. 
DIFFERENTIATION MECHANISMS 
Several possible mechanisms have been proposed for 
differentiation of adult stem cells into other tissues. One mechanism 
that has received attention lately is the possibility of cell fusion, 
whereby the stem cell fuses with a tissue cell and takes on that 
tissue’s characteristics. In vitro experiments using fusion of somatic 
cells with embryonic stem cells and embryonic germ cells^^ have 
demonstrated that the cell hybrid can take on characteristics of the 
more primitively developed cell. However, given that such 
characteristics of spontaneous cell fusion hybrids in vitro have been 
known for quite some time,^^ and that a cell fusion hybrid does not 
explain in vitro differentiation of adult stem cells unexposed to 
tissues, the experiments could not verify this as a possible 
mechanism for adult stem cell differentiation. More recently, in vivo 
experiments have shown that for liver, formation of a cell fusion 
hybrid is a viable explanation for some of the differentiation as well 
as repair of hver damage seen in these experiments. In an in vitro 
experiment where human mesenchymal stem cells were co-cultured 
vvhth heat-shocked small airway epithelial cells, a mixed answer was 
obtained — some of the stem cells differentiated directly into 
epithelial cells, while others formed cell fusion hybrids to repair the 
damage. The ability to form cell hybrids in some tissues may be a 
useful mechanism for repair of certain types of tissue damage or for 
delivery of therapeutic genes to a tissue.^^ The reprogramming of 
cellular gene expression via hybrids is not unhke a novel method 
reported recently for transdifferentiation of somatic cells. In this 
method, fibroblasts were soaked in the cytoplasm and nucleoplasm 
of a lysed, differentiated T lymphocyte cell, taking up factors from the 
exposed “soup” of the cellular contents of the differentiated cell, and 
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