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Journal of Neuroscience Research 87:3554–3567 (2009)





           Intraarterially Delivered Human Umbilical
           Cord Blood-Derived Mesenchymal Stem

           Cells in Canine Cerebral Ischemia



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           Dai-Jung Chung, Chi-Bong Choi, Sung-Ho Lee, Eun-Hee Kang,         1
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           Jae-Hoon Lee, Soo-Han Hwang, Hoon Han, Jong-Hwan Lee,          4
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           Bo-Young Choe, Soo-Yeol Lee, and Hwi-Yool Kim        1 *
           1
           Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University,
           Seoul, Republic of Korea
           2
           Department of Radiology, KyungHee University Medical Center, Seoul, Republic of Korea
           3
           Seoul Cord Blood Bank, Histostem Co., Seoul, Republic of Korea
           4
           Department of Veterinary Anatomy, College of Veterinary Medicine, Konkuk University,
           Seoul, Republic of Korea
           5
           Department of Biomedical Engineering, College of Medicine, The Catholic University of Korea,
           Seoul, Republic of Korea
           6
           Department of Biomedical Engineering, College of Electronics and Information,
           KyungHee University, Yungin Kyungki, Republic of Korea
           The present study examined the effects of human          Stroke is characterized as a focal neurological defi-
           umbilical cord blood-derived mesenchymal stem cells  cit of sudden onset, resulting from a cerebrovascular
           (HUCB-derived MSCs) delivered through the basilar ar-  accident (Garcia, 1992). Causes of strokes include
           tery in a canine thromboembolic brain ischemia model.  obstruction of the blood vessels leading to infarction
           Cerebral ischemia was induced through occlusion of   (ischemic stroke) and rupture of the blood vessel walls
           the middle cerebral artery by injecting thrombus emboli  leading to hemorrhage (hemorrhagic stroke). In the
           into 10 beagles. In the HUCBC group (n 5 5), 1 3 10 6  brain, ischemia progresses to necrosis of neurons and
           HUCB-derived MSCs were transplanted through the      glial elements, resulting in an area of necrotic tissue
           basilar artery 1 day after ischemic induction using an  described as an infarct (Platt and Garosi, 2003; Garosi
           endovascular interventional approach. In the control  et al., 2006).
           group (n 5 5), phosphate-buffered saline (PBS) was       Current therapies for stroke include thrombolytic
           injected in the same manner in as the HUCBC group.   therapy, medication, decompressive surgery to reduce
           Upon neurobehavioral examination, earlier recovery   intracranial pressure, and rehabilitation therapy (Zivin,
           was observed in the HUCBC group. The HUCBC group     2000). Despite these therapies, some patients suffer from
           showed a decrease in the infarction volume at 1 week  permanent neurological deficit from the brain injury. In
           after cerebral ischemic induction, whereas the control  addition, there are several limitations of the current ther-
           group showed an increase in the infarction volume at 1  apeutic approach to cerebral ischemia. Thrombolytic
           week, by magnetic resonance image analysis. Trans-   therapy has a window of only 3 hr or less and has
           planted cells had differentiated into neurons and astro-  limited application (Meschia et al., 2002).
           cytes and were observed in and around endothelial
           cells that were positive for von Willebrand factor (vWF).
           HUCB-derived MSCs expressed neuroprotective fac-
           tors, such as brain-derived neurotrophic factor (BDNF)  Contract grant sponsor: Korea Research Foundation Grant funded by the
           and vascular endothelial growth factor (VEGF), at 4  Korean Government (MOEHRD; Basic Research Promotion Fund);
           weeks after the transplantation. The transplanted cells  Contract grant number: KRF-2008-314-E00625; Contract grant sponsor:
           demonstrated their efficacy by reducing the infarction  Brain Korea 21 Project; Contract grant sponsor: Purpose Basic Research
           lesion volume and through earlier recovery from the  Grant of the KOSEF; Contract grant number: R01-2007-000-20782-0.
           neurological deficit. These results suggest that intraar-  *Correspondence to: Hwi-Yool Kim, Department of Veterinary Surgery,
           terial transplantation of HUCB-derived MSCs could be  College of Veterinary Medicine, Konkuk University, No. 1 Hwayang-
           useful in clinical treatment of cerebral ischemia.  V V 2009  Dong, Kwangjin-Gu, Seoul 143-701, Republic of Korea.
                                                        C
                                                                E-mail: hykim@konkuk.ac.kr
           Wiley-Liss, Inc.
                                                                Received 1 February 2009; Revised 25 April 2009; Accepted 18 May
           Key words: canine; cerebral ischemia; interventional  2009
           endovascular approach; middle cerebral artery occlusion;  Published online 29 June 2009 in Wiley InterScience (www.
           intraarterial transplantation; HUBC-derived MSCs     interscience.wiley.com). DOI: 10.1002/jnr.22162

           ' 2009 Wiley-Liss, Inc.
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