Appendix J. 
301 
that received human MAPC developed a host thymic lymphoma. 
Human MAPC, like mouse MAPC, appeared to differentiate into 
endothelial cells that contribute to tumor angiogenesis. 
Engraftment of MAPC in stroke model: 
In yet another in vivo study we evaluated the effect of 
human MAPC in a rat stroke model. Cortical brain ischemia was 
produced in male rats by permanently ligating the right middle 
cerebral artery distal to the striatal branch. Animals were placed on 
cyclosporine-A and 2 weeks later, 2x10® human MAPC were injected 
around the infarct zone. As controls, animals received normal saline 
or MAPC conditioned medium. Limb placement test and tactile 
stimulation test were blindly assessed 1 week before brain ischemia, 
1 day before transplantation, and at 2 and 6 weeks after grafting. The 
limb placement test included eight subtests described by Johansson 
and coworkers In a tactile stimulation test a small piece of 
adhesive tape was rapidly applied to the radial aspect of each 
forepaw. The rats were then returned to their home cages, and the 
order of the tape removal (i.e., left versus right) was recorded. Three 
to five trials were conducted on each test day. Each trial was 
terminated when the tapes were removed from both forepaws or 
after 3 min. Animals were subsequently sacrificed to determine the 
fate of the human cells injected in the brain. After 2 and 6 weeks, 
animals that received human MAPC scored statistically significantly 
better in the limb placement test as well as tactile stimulation test 
compared with animals that received only cyclosporine-A (CSA), or 
were injected with normal saline or MAPC conditioned medium. The 
level of recuperation of motor and sensory function was 80% of 
animals v\hthout stroke. When the brain was examined for the 
presence and differentiation of human MAPC to neuroectodermal 
cells, we found that human MAPC were present, but remained rather 
immature. Therefore, we cannot attribute the motor and sensory 
improvement to region specific differentiation to neuronal cells and 
integration of neurons derived from MAPC in the host brain. Rather 
the improvement must be caused by trophic effects emanated by the 
human MAPC to either improve vascularization of the ischemic area, 
to support survival of the remaining endogenous neurons, or to 
recruit neuronal progenitors from the host brain. These possibilities 
are currently being evaluated. 
POSSIBLE MECHANISMS UNDERLYING THE PHENOMENON OF 
MULTIPOTENT ADULT PROGENITOR CELLS: 
PRE-PUBLICATION VERSION 
