Motor Function Recovery after Adipose Tissue Derived Mesenchymal Stem Cell Therapy in Rats with Cerebral Infarction

  • Kim, Chang-Hwan (Departments of Neurosurgery, College of Medicine Yeungnam University) ;
  • Kim, Yang-Woon (Departments of Physiology, College of Medicine Yeungnam University) ;
  • Jang, Sung-Ho (Departments of Rehabilitation Medicine, College of Medicine Yeungnam University) ;
  • Chang, Chul-Hoon (Departments of Neurosurgery, College of Medicine Yeungnam University) ;
  • Jung, Jae-Ho (Departments of Plastic Surgery, College of Medicine Yeungnam University) ;
  • Kim, Seong-Ho (Departments of Neurosurgery, College of Medicine Yeungnam University)
  • Published : 2006.10.30

Abstract

Objective : There have been recent reports that mesenchymal stromal cells that are harvested from adipose tissue are able to differentiate into neurons. In the present study, we administered adipose tissue derived stem cells in rats with cerebral infarction in order to determine whether those stem cells could enhance the recovery of motor function. Methods : Cerebral infarction was induced by intraluminal occlusion of middle cerebral artery in rats. The adipose tissue-derived mesenchymal stem cells were harvested from inguinal fat pad and proliferated for 2 weeks in DMEM media. Approximately $1{\times}10^6$ cells were injected intravenously or into subdural space of the peri-lesional area. The rotor rod test was performed at preoperative state[before MCA occlusion], and 1, 2, 3, 4, 6, 8 and 10 weeks after the cell therapy. Results : The motor functions that were assessed by rotor rod test at 1 week of the cell therapy were nearly zero among the experimental groups. However, there was apparent motor function recovery after 2 weeks and 4 weeks of cell injection in intravenously treated rats and peri-lesionaly treated rats, respectively, while there was no significant improvement till 8 weeks in vehicle treated rats. Conclusion : These results demonstrate that the adipose derived stem cell treatment improves motor function recovery in rats with cerebral infarction.

References

  1. Arvidsson A, Collin T, Kirik D, Kokaia Z, Linvall O : Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8 : 963-970, 2002 https://doi.org/10.1038/nm747
  2. Burns JS, Abdallah BM, Guldberg P, Rygaard J, Schroder HD, Kassem M : Tumorigenic heterogeneity in cancer stem cells evolved from long-term cultures of telomerase-immortalized human mesenchymal stem cells. Cancer Res 65 : 3126-3135, 2005 https://doi.org/10.1158/0008-5472.CAN-04-2218
  3. Chaudhari M, Cornelius JG, Schatz D, Peck AB, Ramiya VK : Pancreatic stem cells : a therapeutic agent that may offer the best approach for curing type 1 diabetes. Pediatr Diabetes 2 : 195-202, 2001 https://doi.org/10.1034/j.1399-5448.2001.20410.x
  4. Chu K, Kim M, Park KJ, Jeong SW, Park HK, Jung KH, et al : Human neural stem cells improve sensorimotor deficits in the adult rat brain with experimental focal ischemia. Brain Res 1016 : 145-153, 2004 https://doi.org/10.1016/j.brainres.2004.04.038
  5. Crevensten G, Walsh AJ, Ananthakrishnan D, Page P, Wahba GM, Lotz JC, et al : Intervertebral disc cell therapy for regeneration : mesenchymal stem cell implantation in rat intervertebral discs. Ann Biomed Eng 32 : 430-434, 2004 https://doi.org/10.1023/B:ABME.0000017545.84833.7c
  6. Gorio A, Torrente Y, Madaschi L, Di Stefano AB, Pisati F, Marchesi C, et al : Fate of autologous dermal stem cells transplanted into the spinal cord after traumatic injury(TSCI). Neuroscience 125 : 179-189, 2004 https://doi.org/10.1016/j.neuroscience.2003.10.046
  7. Hanabusa K, Nagaya N, Iwase T, Itoh T, Murakami S, Shimizu Y, et al : Adrenomedullin enhances therapeutic potency of mesenchymal stem cells after experimental stroke in rats. Stroke 36 : 853-858, 2005 https://doi.org/10.1161/01.STR.0000157661.69482.76
  8. Honma T, Honmou O, Iihoshi S, Harada K, Houkin K, Hamada H, et al : Intravenous infusion of immortalized human mesenchymal stem cells protects against injury in a cerebral ischemia model in adult rat. Exp Neurol(in press) 2005
  9. Jin K, Sun Y, Xie L, Mao XO, Childs J, Peel A, et al : Comparison of ischemia-directed migration of neural precursor cells after intrastriatal, intraventricular, or intravenous transplantation in the rat. Neurobiol Dis 18 : 366-374, 2005 https://doi.org/10.1016/j.nbd.2004.10.010
  10. Kang SK, Lee HL, Bae YC, Kim HK, Baik SY, Jung JS : Improvement of neurological deficits by intracerebral transplantation of human adipose tissue-derived stromal cels after cerebral ischemia in rats. Exp Neurol 183 : 355-366, 2003 https://doi.org/10.1016/S0014-4886(03)00089-X
  11. Kokai LE, Rubin JP, Marra KG : The potential of adipose-derived adult stem cells as a source of neuronal progenitor cells. Plast Reconstr Surg 116 : 1453-1460, 2005 https://doi.org/10.1097/01.prs.0000182570.62814.e3
  12. Kokaia Z, Lindvall O : Neurogenesis after ischemic brain insults. Curr Opin Neurobiol 13 : 127-132, 2003 https://doi.org/10.1016/S0959-4388(03)00017-5
  13. Lee IW : Stem cells and neurosurgery. J Korean neurosurg Soc 33 : 1-12, 2003
  14. Modo M, Rezaie P, Heuschling P, Patel S, Male DK, Hodges H : Transplantation of neural stem cells in a rat model of stroke : assessment of short-term graft survival and acute host immunological response. Brain Res 958 : 70-82, 2002 https://doi.org/10.1016/S0006-8993(02)03463-7
  15. Nagaya N, Fujii T, Iwase T, Ohgushi H, Itoh T, Uematsu M, et al : Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287 : 2670-2676, 2004 https://doi.org/10.1152/ajpheart.01071.2003
  16. Rubio D, Garcia-Castro J, Martin MC, de la Fuente R, Cigudosa JC, Lloyd AC, et al : Spontaneous human stem cell transformation. Cancer Res 65 : 3035-3039, 2005 https://doi.org/10.1158/0008-5472.CAN-04-4194
  17. Schachinger V, Zeiher AM : Stem cells and cardiovascular and renal disease : today and tomorrow. J Am Soc Nephrol(Suppl 1) 16 : S2-6, 2005 https://doi.org/10.1681/ASN.2004110971
  18. Strem BM, Hicok KC, Zhu M, Wulur I, Alfonso Z, Schreiber RE, et al : Multipotential differentiation of adipose tissue-derived stem cells. Keio J Med 54 : 132-141, 2005 https://doi.org/10.2302/kjm.54.132
  19. Vendrame M, Cassady J, Newcomb J, Butler T, Pennypacker KR, Zigova T, et al : Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke 35 : 2390-2395, 2004 https://doi.org/10.1161/01.STR.0000141681.06735.9b