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HUCB-Derived MSCs in Canine Cerebral Ischemia 3559

Fig. 6. Comparison of ischemic lesion volume change between Fig. 7. Number of WBCs between HUCBC and control group.
HUCBC and control groups after cerebral ischemia at day 1, week There is no significant increase in the number of WBC in HUCBC
1, and week 2 (*P < 0.05, yP < 0.05). There is a significant group after transplantation of HUBC-derived MSCs. Arrow indicates
decrease in MRI-estimated lesion volume in the HUCBC group and transplantation time.
increase in MRI-estimated lesion volume in control group between
day 1 and week 1.
motor dysfunction (hemiplegia, postural reaction deficit),
reduced reponsiveness, circling, head turning, and hemi-
TABLE I. Changes of Lesion Volume Percentage at Weeks
1 and 2 Compared With Lesion Volume at Day 1 in apnosia. Neurobehavioral symptoms gradually improved
Experimented Dogs until reaching normal recovery at 4 weeks in both
groups. The two dogs that showed no definite neuro-
Ischemic lesion volume in percentage logical deficit 1 day after cerebral ischemic induction
Groups Day 1 Week 1 Week 2 were excluded from the neurological evaluation. The
HUCBC group had a lower deficit score than the con-
HUCBC 100 75.42 6 11.36* 71.34 6 35.44 trol group throughout the study period. There was sig-
Control 100 155.15 6 24.50* 115.18 6 29.29
nificant difference (P > 0.05) between the two groups
*P < 0.05. on days 7, 10, and 22 (Fig. 4).
RESULTS
Identification of Cerebral Ischemia Induction
Change in Ischemic Lesion Volumes
Prior to the HUCBC transplantation, induction of by MRI Analysis
cerebral ischemia was identified. Patency of the cerebral
arteries, including the MCA, was confirmed by angiog- FLAIR coronal brain MR images of all experimen-
raphy prior to the cerebral ischemic induction. At 30 tal animals were obtained 1 day after cerebral ischemic
min after the thrombus injection, occlusion of the MCA induction and 1 and 2 weeks after intraarterial delivery
was observed in all dogs. No recanalization occurred of HUCB-derived MSCs and PBS (Fig. 5). In the
(Fig. 2). HUCBC group, the lesion volume progressively
The lesioned area showed a high signal intensity in decreased from day 1 to week 2 after lesion induction,
T2-weighted and FLAIR MR images and a low signal with a significant difference between day 1 and week 1
intensity in T1-weighted MR images. Abnormal signal (20.86 6 4.90%, n 5 5, vs. 15.97 6 5.4%, n 5 5; P <
intensities were found mainly in the MCA territories, 0.05). In the control group (sham control, PBS injection
basal ganglia, and thalamus. Slight contrast enhancement alone), there was a significant increase in the lesion vol-
was also observed in T1-weighted MR images. A mass ume between day 1 and week 1 (15.29 6 6.12%, n 5 5
effect resulting from brain swelling was also identified vs. 23.67 6 9.69%, n 5 5; P < 0.05). There was a sig-
(Fig. 3). nificant decrease in the MRI-estimated lesion volume in
the HUCBC group and an increase in the MRI-esti-
mated lesion volume in the control group between day
Neurological Evaluation 1 and week 1 (Figs. 5, 6).
Neurobehavioral signs were evaluated with a neu- When the lesion volume was measured as a per-
rologic scoring system described for previous studies centage of the lesion volume on day 1, there was a
(Purdy et al., 1989; Corbet et al., 1999). At 12 hr after significant difference in the lesion volume percentage
the induction of cerebral ischemia, all dogs but one from between the HUCBC and the control groups at week 1
each group showed signs of neurological deficit such as (75.42 6 11.36% in the HUCBC group, n 5 5 vs.

Journal of Neuroscience Research