314 
Monitoring Stem Cell Research 
began expressing functional characteristics of a T cell.^® 
In contrast to the results discussed above, other experiments 
have shown no evidence that cell fusion plays a role in differentiation 
of adult stem cells into other tissue types. For example, using human 
subjects it was shown that human bone marrow cells differentiated 
into buccal epithelial cells in vivo without cell fusion,^^ and human 
cord blood stem cells formed hepatocytes in mouse liver without 
evidence of cell fusion.^® In these cases it appears that the adult 
stem cells underwent changes in gene expression and directly 
differentiated into the host tissue cell type, integrating into the 
tissue. It is likely that the mechanism of adult stem cell 
differentiation may vary depending on the target tissue, or possibly 
on the state of the adult stem cell used, especially given that normal 
functioning liver typically shows cell fusion hybrids, with cell fusion 
functioning as a mechanism for most of the differentiation and repair 
in tissues such as liver, and direct differentiation 
(transdifferentiation) into other cell types functioning in other 
tissues. Much remains to be determined regarding the mechanisms 
associated with adult stem cell differentiation. 
Keeping in mind the uncertainties noted above for 
identification of a particular adult stem cell and its initial tissue of 
origin, the majority of this review will focus on some of the evidence 
for adult stem cell differentiation into other tissues. The cells whll be 
categorized based on general tissue of isolation, with the primary 
emphasis on human adult stem cells, supplemented "with information 
from animal studies. 
BONE MARROW STEM CELLS 
Bone marrow contains at least two, and likely more,^'^® 
discernable stem cell populations. Besides the hematopoietic stem 
cell which produces blood cell progeny, a cell type termed 
mesenchymal or stromal also exists in marrow. This cell provides 
support for hematopoietic and other cells within the marrow, and has 
also been a focus for possible tissue repair.®® Isolation is typically 
based on some cell surface markers, but also primarily on the ability 
of these cells to form adherent cell layers in culture. Human 
mesenchymal stem cells have been shown to differentiate in vitro 
into various cell lineages including neuronal cells, as well as 
Ccirtilage, bone, and fat lineages.®® In vivo, human adult 
mesenchymal stem cells transferred in utero into fetal sheep can 
integrate into multiple tissues, persisting for over a year. The cells 
PRE-PUBLICATION VERSION 
