Journal of Korean Neurosurgical Society

  • 제48권5호
  • /
  • Pages.391-398
  • /
  • 2010
  • /
  • 2005-3711(pISSN)
  • /
  • 1598-7876(eISSN)
대한신경외과학회 (The Korean Neurosurgical Society)
권호 표지
DOI QR코드

DOI QR Code

In vivo Tracking of Transplanted Bone Marrow-Derived Mesenchymal Stem Cells in a Murine Model of Stroke by Bioluminescence Imaging

  • Jang, Kyung-Sool (Department of Neurosurgery, Institute of Catholic Integrative Medicine (ICIM) of Incheon St. Mary's Hospital, The Catholic University of Korea) ;
  • Lee, Kwan-Sung (Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea) ;
  • Yang, Seung-Ho (Department of Neurosurgery, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Jeun, Sin-Soo (Department of Neurosurgery, Seoul St. Mary's Hospital, The Catholic University of Korea)
  • 투고 : 2009.07.28
  • 심사 : 2010.11.25
  • 발행 : 2010.11.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective : This study was designed to validate the cell trafficking efficiency of the in vivo bioluminescence image (BLI) study in the setting of transplantation of the luciferase expressing bone marrow-derived mesenchymal stem cells (BMSC), which were delivered at each different time after transient middle cerebral artery occlusion (MCAO) in a mouse model. Methods : Transplanting donor BMSC were prepared by primary cell culture from transgenic mouse expressing luciferase (LUC). Transient focal infarcts were induced in 4-6-week-old male nude mice. The experiment mice were divided into five groups by the time of MSC transplantation : 1) sham-operation group, 2) 2-h group, 3) 1-day group, 4) 3-day group, and 5) 1-week group. BLI for detection of spatial distribution of transplanted MSC was performed by detecting emitted photons. Migration of the transplanted cells to the infarcted area was confirmed by histological examinations. Differences between groups were evaluated by paired t-test. Results : A focal spot of bioluminescence was observed at the injection site on the next day after transplantation by Signal intensity of bioluminescence. After 4 weeks, the mean signal intensities of 2-h, 1-day, 3-day, and 1-week group were $2.6{\times}10^7{\pm}7.4{\times}10^6$. $6.1{\times}10^6{\pm}1.2{\times}10^6$, $1.7{\times}10^6{\pm}4.4{\times}10^5$, and $8.9{\times}10^6{\pm}9.5{\times}10^5$, respectively. The 2-h group showed significantly higher signal intensity (p<0.01). The engrafted BMSC showed around the infarct border zones on immunohistochemical examination. The counts of LUC-positive cells revealed the highest number in the 2-h group, in agreement with the results of BLI experiments (p<0.01). Conclusion : In this study, the results suggested that the transplanted BMSC migrated to the infarct border zone in BLI study and the higher signal intensity of LUC-positive cells seen in 2 hrs after MSC transplantation in MCAO mouse model. In addition, noninvasive imaging in real time is an ideal method for tracking stem cell transplantation. This method can be widely applied to various research fields of cell transplantation therapy.

키워드

참고문헌

  1. Aboody KS, Brown A, Rainov NG, Bower KA, Liu S, Yang W, et al. : Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas. Proc Natl Acad Sci U S A 97 : 12846-12851, 2000 https://doi.org/10.1073/pnas.97.23.12846
  2. Bang OY, Lee JS, Lee PH, Lee G : Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol 57 : 874-882, 2005 https://doi.org/10.1002/ana.20501
  3. Borlongan CV, Tajima Y, Trojanowski JQ, Lee VM, Sanberg PR : Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats. Exp Neurol 149 : 310-321, 1998 https://doi.org/10.1006/exnr.1997.6730
  4. Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, Lu M, et al. : Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 73 : 778-786, 2003 https://doi.org/10.1002/jnr.10691
  5. Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, et al. : Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 32 : 1005-1011, 2001 https://doi.org/10.1161/01.STR.32.4.1005
  6. Chopp M, Li Y : Treatment of neural injury with marrow stromal cells. Lancet Neurol 1 : 92-100, 2002 https://doi.org/10.1016/S1474-4422(02)00040-6
  7. Clark RK, Lee EV, White RF, Jonak ZL, Fenerstein GZ, Barone FC : Reperfusion following focal stroke hastens inflammation and resolution of ischemic injured tissue. Brain Res Bull 35 : 387-392, 1994 https://doi.org/10.1016/0361-9230(94)90119-8
  8. Contag CH, Spilman SD, Contag PR, Oshiro M, Eames B, Dennery P, et al. : Visualizing gene expression in living mammals using a bioluminescent reporter. Photochem Photobiol 66 : 523-531, 1997 https://doi.org/10.1111/j.1751-1097.1997.tb03184.x
  9. Kim DE, Schellingerhout D, Ishii K, Shah K, Weissleder R : Imaging of stem cell recruitment to ischemic infarcts in a murine model. Stroke 35 : 952-957, 2004 https://doi.org/10.1161/01.STR.0000120308.21946.5D
  10. Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, Scadden DT, et al. : Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells. Nat Biotechnol 18 : 410-414, 2000 https://doi.org/10.1038/74464
  11. Iihoshi S, Honmou O, Houkin K, Hashi K, Kocsis JD : A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats. Brain Res 1007 : 1-9, 2004 https://doi.org/10.1016/j.brainres.2003.09.084
  12. Li Y, Chen J, Chen XG, Wang L, Gautam SC, Xu YX, Katakowski M, et al. : Human marrow stromal cell therapy for stroke in rat : neurotrophins and functional recovery. Neurology 59 : 514-523, 2002 https://doi.org/10.1212/WNL.59.4.514
  13. Li Y, Chen J, Wang L, Lu M, Chopp M : Treatment of stoke in rat with intracarotid administration of marrow stromal cells. Neurology 56 : 1666-1672, 2001 https://doi.org/10.1212/WNL.56.12.1666
  14. Li Y, Chen J, Zhang CL, Wang L, Lu D, Katakowski M, et al. : Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia 49 : 407-417, 2005 https://doi.org/10.1002/glia.20126
  15. Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX, et al. : Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 20 : 1311-1319, 2000 https://doi.org/10.1097/00004647-200009000-00006
  16. Lo EH, Dalkara T, Moskowitz MA : Mechanisms,challenges and opportunities in stroke. Nat Rev Neurosci 4 : 399-415, 2003
  17. Longa EZ, Weinstein PR, Carlson S, Cummins R : Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20 : 84-91, 1989 https://doi.org/10.1161/01.STR.20.1.84
  18. Mahmood A, Lu D, Wang L, Li Y, Lu M, Chopp M : Treatment of traumatic brain injury in female rats with intravenous administration of bone marrow stromal cells. Neurosurgery 49 : 1196-1203, 2001
  19. Modo M, Stroemer RP, Tang E, Patel S, Hodges H : Effects of implantation site of stem cell grafts on behavioral recovery from stroke damage. Stroke 33 : 2270-2278, 2002 https://doi.org/10.1161/01.STR.0000027693.50675.C5
  20. Ourednik V, Ourednik J, Park KI, Snyder EY : Neural stem cells--a versatile tool for cell replacement and gene therapy in the central nervous system. Clin Genet 56 : 267-278, 1999 https://doi.org/10.1034/j.1399-0004.1999.560403.x
  21. Paxinos G, Watson C, Pennisi M, Topple A : Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. J Neurosci Methods 13 : 139-143, 1985 https://doi.org/10.1016/0165-0270(85)90026-3
  22. Prockop DJ : Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276 : 71-74, 1997 https://doi.org/10.1126/science.276.5309.71
  23. Rempe DA, Kent TA : Using bone marrow stromal cells for treat-ment of stroke. Neurology 59 : 486-487, 2002 https://doi.org/10.1212/WNL.59.4.486
  24. Shen LH, Li Y, Chen J, Zacharek A, Gao Q, Kapke A, et al. : Therapeutic benefit of bone marrow stromal cells administered 1 month after stroke. J Cereb Blood Flow Metab 27 : 6-13, 2007 https://doi.org/10.1038/sj.jcbfm.9600311
  25. Shichinohe H, Kuroda S, Yano S, Hida K, Iwasaki Y : Role of SDF-1/CXCR4 system in survival and migration of bone marrow stromal cells after transplantation into mice cerebral infarct. Brain Res 1183 : 138-147, 2007 https://doi.org/10.1016/j.brainres.2007.08.091
  26. Snyder EY, Deitcher DL, Walsh C, Arnold-Aldea S, Hartwieg EA, Cepko CL : Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell 68 : 33-51, 1992 https://doi.org/10.1016/0092-8674(92)90204-P
  27. Wang L, Li Y, Chen J, Gautam SC, Zhang Z, Lu M, et al. : Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Exp Hematol 30 : 831-836, 2002 https://doi.org/10.1016/S0301-472X(02)00829-9
  28. Wang Y, Deng Y, Zhou GQ : SDF-1alpha/CXCR4-mediated migration of systemically transplanted bone marrow stromal cells towards ischemic brain lesion in a rat model. Brain Res 1195 : 104-112, 2008 https://doi.org/10.1016/j.brainres.2007.11.068
  29. Zhang ZG, Jiang Q, Zhang R, Zhang L, Wang L, Zhang L, et al. : Magnetic resonance imaging and neurosphere therapy of stroke in rat. Ann Neurol 53 : 259-263, 2003 https://doi.org/10.1002/ana.10467
  30. Zhao MZ, Nonoguchi N, Ikeda N, Watanabe T, Furutama D, Miyazawa D, et al. : Novel therapeutic strategy for stroke in rats by bone marrow stromal cells and ex vivo HGF gene transfer with HSV-1 vector. J Cereb Blood Flow Metab 26: 1176-1188, 2006 https://doi.org/10.1038/sj.jcbfm.9600273

피인용 문헌

  1. The potential of stem cell therapy for stroke: is PISCES the sign? vol.26, pp.6, 2010, https://doi.org/10.1096/fj.11-195719
  2. Mesenchymal Bone Marrow Cell Therapy in a Mouse Model of Chagas Disease. Where Do the Cells Go? vol.6, pp.12, 2010, https://doi.org/10.1371/journal.pntd.0001971
  3. Regulation of Immunity via Multipotent Mesenchymal Stromal Cells vol.4, pp.1, 2010, https://doi.org/10.32607/20758251-2012-4-1-23-31
  4. Granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells for the treatment of ischemic stroke vol.7, pp.16, 2012, https://doi.org/10.3969/j.issn.1673-5374.2012.16.003
  5. Dynamic Imaging of Marrow-Resident Granulocytes Interacting with Human Mesenchymal Stem Cells upon Systemic Lipopolysaccharide Challenge vol.2013, pp.None, 2013, https://doi.org/10.1155/2013/656839
  6. Effects of MSC Coadministration and Route of Delivery on Cord Blood Hematopoietic Stem Cell Engraftment vol.22, pp.7, 2010, https://doi.org/10.3727/096368912x657431
  7. Challenges facing in vivo tracking of mesenchymal stem cells used for tissue regeneration vol.11, pp.1, 2010, https://doi.org/10.1586/17434440.2014.865306
  8. Tracking Fusion of Human Mesenchymal Stem Cells After Transplantation to the Heart vol.4, pp.6, 2010, https://doi.org/10.5966/sctm.2014-0198
  9. Chimeric Mouse model to track the migration of bone marrow derived cells in glioblastoma following anti-angiogenic treatments vol.17, pp.3, 2010, https://doi.org/10.1080/15384047.2016.1139243
  10. In Vivo Tracking of Systemically Administered Allogeneic Bone Marrow Mesenchymal Stem Cells in Normal Rats through Bioluminescence Imaging vol.2016, pp.None, 2010, https://doi.org/10.1155/2016/3970942
  11. Potential Therapeutic Mechanisms and Tracking of Transplanted Stem Cells: Implications for Stroke Treatment vol.2017, pp.None, 2010, https://doi.org/10.1155/2017/2707082
  12. Non-invasive in vivo molecular imaging of intra-articularly transplanted immortalized bone marrow stem cells for osteoarthritis treatment vol.8, pp.57, 2010, https://doi.org/10.18632/oncotarget.21315
  13. Biocompatibility of two model elastin‐like recombinamer‐based hydrogels formed through physical or chemical cross‐linking for various applications in tissue engineering and regene vol.12, pp.3, 2010, https://doi.org/10.1002/term.2562
  14. The Critical Role of Cell Homing in Cytotherapeutics and Regenerative Medicine vol.2, pp.1, 2019, https://doi.org/10.1002/adtp.201800098
  15. Triple-modal imaging of stem-cells labeled with multimodal nanoparticles, applied in a stroke model vol.11, pp.2, 2010, https://doi.org/10.4252/wjsc.v11.i2.100
  16. Bidirectional Enhancement of Cell Proliferation Between Iron Oxide Nanoparticle-Labeled Mesenchymal Stem Cells and Choroid Plexus in a Cell-Based Therapy Model of Ischemic Stroke vol.15, pp.None, 2020, https://doi.org/10.2147/ijn.s278687