Appendix K. 
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marker. Interestingly, only a low percentage of donor cells were 
identified as integrating into the regenerating pancreas, with most of 
the regeneration due to induced proliferation and differentiation of 
endogenous pancreatic cell precursors, suggesting that the bone 
marrow stem cells provided growth signals for the tissue 
regeneration. 
Heart, as a mesodermally-derived organ, is a likely candidate 
for regeneration with bone marrow derived stem cells. Numerous 
references now document the ability of these adult stem cells to 
contribute to regeneration of cardiac tissue and improve performance 
of damaged hearts. In animal studies, for example, rat®®, mouse^°'^^’^^ 
and human^®’^'^ stem cells have been identified as integrating into 
cardiac tissue, forming cardiomyocytes and/or cardiac blood vessels, 
regenerating infarcted heart tissue, and improving cardiac function. 
In mice, bone marrow derived stem cells injected into old animals 
seems capable of restoring cardiac function,^® apparently through 
increased activity for cardiac blood vessel formation. One fascinating 
study using xenogeneic (cross-species) transplants suggests that 
stromal cells may show immune tolerance by the host.^® Mouse 
marrow stromal cells were transplanted into fully immunocompetent 
rats, and contributed formation of cardiomyocytes and cardiac 
vessels. Even after 13 weeks, the mouse cells were not rejected by 
the rat hosts. Evidence has accumulated from postmortem studies 
that bone marrow stem cells can contribute to cardiomyocytes after 
damage to the human heart as well.^’^® The evidence has led 
numerous groups to use bone marrow derived stem cells in 
treatment of patients with damaged cardiac tissue.’®®°®^ ®^ Results 
from these clinical trials indicate that bone marrow derived stem 
cells, including cells from the patients themselves, can regenerate 
damaged cardiac tissue and improve cardiac performance in 
humans. In terms of restoring angiogenesis and improving blood 
circulation, results in patients are not limited to the heart. Tateishi- 
Yuyama et a/.®® have shown that bone marrow derived stem cells 
ffom the patients themselves can improve blood circulation in 
gangrenous limbs, in many cases obviating the need for amputation. 
Bone marrow derived adult stem cells have also been found 
to contribute to various other adult tissues. Animal studies indicate 
evidence that bone marrow stem cells can contribute as progenitors 
of lung epithelial tissue®"^, and mesenchymal stem cells can home to 
damaged lung tissue, engraft, and take on an epithelial morphology, 
participating in repair and reduction of inflammation.®® Bone marrow 
derived stem cells also have been shown to contribute to 
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