Yıl: 2012 Cilt: 22 Sayı: 2 Sayfa Aralığı: 207 - 217 Metin Dili: Türkçe

Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation

Öz:
AMAÇ: Bu çalışmada omurilik hasarı sonrası sıçan kemik iliği-mezenkimal kök hücrelerinin (sKİ-MKH) lezyon yerindeki etkisini analiz etmek ve transplantasyon sonrası işlevsel iyileşmeyi gözlemlemek amaçlandı. YÖNTEM ve GEREÇLER: MKH’ler sıçan femur ve tibialarından izole edildi. Deney sıçanları dört gruba ayrıldı: sadece laminektomi (1), laminektomi+ travma (2); laminektomi + travma + PBS (3); laminektomi + travma + MKH’ler (4). Sıçanların hareketleri düzenli olarak skorlandı. Dört hafta sonra sıçanlar sakrifiye edildi, omurilikleri immün boyamayla GFP işaretli sKİ-MKH’lerle incelendi. BULGULAR: Erken posttravmatik dönemde, Grup 4’teki omurilik dokusu ultrastrüktürel olarak korundu. Santral kanalın etrafındaki ependimal bölgeyi oluşturan hücrelerinin çoğu MKH’ler olarak saptandı. Ependimal bölgenin etrafındaki gri ve ak maddeler astrositik görünümlü Nestin+/ GFAP+ hücrelerden oluşmuştu. Grup 4’te özellikle arka bacak fonksiyonlarında motor iyileşme belirgindi. Buna karşın, diğer gruplarda belirgin değişiklik izlenmedi. SONUÇ: Ependimal bölgenin etrafındaki gri ve ak maddede Nestin+/GFAP+ hücrelerin artışı kendini yenileme ve plastisite potansiyellerini gösterebilir ve sKİ-MKH’lerin transplantasyonu spinal kord travması sonrası fonksiyonel iyileşmede etkili bir strateji olabilir. Sonuç olarak, moleküler faktörler hücre kaderini belirleyen hücre tabanlı tedavinin onarıcı potansiyelini artırmak için uygulanabilir.
Anahtar Kelime:

Omurilik hasarlı sıçanlarda kemik iliği kaynaklı mezenkimal kök hücre transplantasyonu sonrası lezyonda azalma ve harekette kısmi işlevsel iyileşme

Öz:
AIm: This study aimed to analyze the effect of rat bone marrow-mesenchymal stem cells (rBM-MSCs) delivery on lesion site after spinal cord injury, and to observe the functional recovery after transplantation. MaterIal and Methods: MSCs were isolated from rat femurs and tibias. The experimental rat population was divided into four groups: only laminectomy (1); laminectomy+trauma (2); laminectomy+trauma+PBS (3); laminectomy+trauma+MSCs (4). Their motility were scored regularly. After 4-weeks, rats were sacrificed, and their spinal cords were examined for GFP labeled rBM-MSCs by immunostainings. Results: In the early posttraumatic period, the ultrastructures of spinal cord tissue were preserved in Group 4. The majority of cells forming the ependymal region around the central canal were found to be MSCs. The gray-and-white-matter around the ependymal region were composed of Nestin+/GFAP+ cells, with astrocytic-like appearance. The scores showed significant motor recovery in Group 4, especially in hind limb functions. However, no obvious change was observed in other groups. ConclusIon: The increase Nestin+/GFAP+ cells in the gray-and-white-matter around the ependymal region could indicate the potential to self-renew and plasticity. Thus, transplantation of rBM-MSCs might be an effective strategy to improve functional recovery following spinal cord trauma. In conclusion, molecular factors in cell fate decisions could be manipulated to enhance reparative potential of cell-based therapy.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Basso DM, Beattie MS, Bresnahan JC: A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma 12: 1-21, 1995
  • 2. Choi H, Liao WL, Newton KM, Onario RC, King AM, Desilets FC, Woodard EJ, Eichler ME, Frontera WR, Sabharwal S, Teng YD: Respiratory abnormalities resulting from midcervical spinal cord injury and their reversal by serotonin 1A agonists in conscious rats. J Neurosci 25(18): 4550-4559, 2005
  • 3. Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, Lu M, Rosenblum M: Spinal cord injury in rat: Treatment with bone marrow stromal cell transplantation. Neuroreport 11: 3001–3005, 2000
  • 4. De Macedo Braga LM, Lacchini S, Schaan BD, Rodrigues B, Rosa K, De Angelis K, Borges LF, Irigoyen MC, Nardi NB: In situ delivery of bone marrow cells and mesenchymal stem cells improves cardiovascular function in hypertensive rats submitted to myocardial infarction. J Biomed Sci 15: 365-374, 2008
  • 5. Ding DC, Shyu WC, Chiang MF, Lin SZ, Chang YC, Wang HJ, Su CY, Li H: Enhancement of neuroplasticity through upregulation of beta1-integrin in human umbilical cord- derived stromal cell implanted stroke model. Neurobiol Dis 27(3):339-353, 2007
  • 6. Grove JE, Bruscia E, Krause DS: Plasticity of bone marrow– derived stem cells. Stem cells 22 (4):487–500, 2004
  • 7. Joosten EA, Veldhuis WB, Hamers FP: Collagen containing neonatal astrocytes stimulates regrowth of injured fibers and promotes modest locomotor recovery after spinal cord injury. J Neurosci Res 77: 127–142, 2004
  • 8. Kabatas S, Teng YD: Potential roles of the neural stem cell in the restoration of the injured spinal cord: Review of the literature. Review. Turk Neurosurg 20(2): 103-110, 2010
  • 9. Karaoz E, Aksoy A, Ayhan S, Sariboyaci AE, Kaymaz F, Kasap M: Characterization of mesenchymal stem cells from rat bone marrow: Ultrastructural properties, differentiation potential and immunophenotypic markers. Histochem Cell Biol 132: 533-546, 2009
  • 10. Lee J, Kuroda S, Shichinohe H, Ikeda J, Seki T, Hida K, Tada M, Sawada K, Iwasaki Y: Migration and differentiation of nuclear fluorescence-labeled bone marrow stromal cells after transplantation into cerebral infarct and spinal cord injury in mice. Neuropathology 23:169 –180, 2003
  • 11. Long X, Olszewski M, Huang W, Kletzel M: Neural cell differentiation in vitro from adult human bone marrow mesenchymal stem cells. Stem Cells Dev 14(1):65-69, 2005
  • 12. Parr AM, Kulbatski I, Wang XH, Keating A, Tator CH: Fate of transplanted adult neural stem/progenitor cells and bone marrow-derived mesenchymal stromal cells in the injured adult rat spinal cord and impact on functional recovery. Surg Neurol 70: 600–607, 2008
  • 13. Parr AM, Kulbatski I, Zahir T, Wang X, Yue C, Keating A, Tator CH: Transplanted adult spinal cord–derived neural stem/ progenitor cells promote early functional recovery after rat spinal cord injury. Neuroscience 155: 760–770, 2008
  • 14. Parr AM, Tator CH, Keating A: Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant 40:609 – 619, 2007
  • 15. Tator CH: Review of treatment trials in human spinal cord injury: Issues, difficulties, and recommendations. Neurosurgery 59:957–982, 2006
  • 16. Teng YD, Liao WL, Choi H, Konya D, Sabharwal S, Langer R, Sidman RL, Snyder EY, Frontera WR: Physical activity-mediated functional recovery after spinal cord injury: Potential roles of neural stem cells. Review. Regen Med 1: 763-776, 2006
  • 17. Teng YD, Wrathall JR: Local blockade of sodium channels by tetrodotoxin ameliorates tissue loss and long-term functional deficits resulting from experimental spinal cord injury. J Neurosci 17(11): 4359-4366, 1997
  • 18. Tobias CA, Han SS, Shumsky JS, Kim D, Tumolo M, Dhoot NO, Wheatley MA, Fischer I, Tessler A, Murray M: Alginate encapsulated BDNF-producing fibroblast grafts permit recovery of function after spinal cord injury in the absence of immune suppression. J Neurotrauma 22: 138–156, 2005
  • 19. Weiss ML, Medicetty S, Bledsoe AR, Rachakatla RS, Choi M, Merchav S, Luo Y, Rao MS, Velagaleti G, Troyer D: Human umbilical cord matrix stem cells: Preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 24(3):781-792, 2006
  • 20. Widenfalk J, Lundströmer K, Jubran M, Brene S, Olson L: Neurotrophic factors and receptors in the immature and adult spinal cord after mechanical injury or kainic acid. J Neurosci 21: 3457–3475, 2001
  • 21. Wu S, Suzuki Y, Ejiri Y, Noda T, Bai H, Kitada M, Kataoka K, Ohta M, Chou H, Ide C: Bone marrow stromal cells enhance differ-entiation of cocultured neurosphere cells and promote regeneration of injured spinal cord. J Neurosci Res 72: 343–351, 2003
  • 22. Xie F, Zheng B: White matter inhibitors in CNS axon regeneration failure. Exp Neurol 209: 302–312, 2008
  • 23. Yang CC, Shih YH, Ko MH, Hsu SY, Cheng H, Fu YS: Transplantation of human umbilical mesenchymal stem cells from Wharton’s jelly after complete transection of the rat spinal cord. PLoS One 3(10):e3336, 2008
APA KARAÖZ E, KABATAŞ S, DURUKSU G, OKCU A, SUBASI C, AY B, MÜSLÜMAN M, CİVELEK E (2012). Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation. Turkish Neurosurgery, 22(2), 207 - 217.
Chicago KARAÖZ ERDAL,KABATAŞ SERDAR,DURUKSU GÖKHAN,OKCU Alparslan,SUBASI Cansu,AY Birol,MÜSLÜMAN Murat,CİVELEK Erdinç Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation. Turkish Neurosurgery 22, no.2 (2012): 207 - 217.
MLA KARAÖZ ERDAL,KABATAŞ SERDAR,DURUKSU GÖKHAN,OKCU Alparslan,SUBASI Cansu,AY Birol,MÜSLÜMAN Murat,CİVELEK Erdinç Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation. Turkish Neurosurgery, vol.22, no.2, 2012, ss.207 - 217.
AMA KARAÖZ E,KABATAŞ S,DURUKSU G,OKCU A,SUBASI C,AY B,MÜSLÜMAN M,CİVELEK E Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation. Turkish Neurosurgery. 2012; 22(2): 207 - 217.
Vancouver KARAÖZ E,KABATAŞ S,DURUKSU G,OKCU A,SUBASI C,AY B,MÜSLÜMAN M,CİVELEK E Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation. Turkish Neurosurgery. 2012; 22(2): 207 - 217.
IEEE KARAÖZ E,KABATAŞ S,DURUKSU G,OKCU A,SUBASI C,AY B,MÜSLÜMAN M,CİVELEK E "Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation." Turkish Neurosurgery, 22, ss.207 - 217, 2012.
ISNAD KARAÖZ, ERDAL vd. "Reduction of lesion in injured rat spinal cord and partial functional recovery of motility after bone marrow derived mesenchymal stem cell transplantation". Turkish Neurosurgery 22/2 (2012), 207-217.