인체 지방조직에서 유래한 줄기세포의 신경세포 분화능 및 신경재생 유도효과

The Effects of Adipose Derived Stem Cells on Neurogenic Differentiation and Induction of Nerve Regeneration

  • 전영준 (가톨릭대학교 의과대학 성형외과학교실) ;
  • 이종원 (가톨릭대학교 의과대학 성형외과학교실) ;
  • 최윤석 (가톨릭대학교 의과대학 성형외과학교실) ;
  • 김영진 (가톨릭대학교 의과대학 성형외과학교실) ;
  • 김성은 (가톨릭대학교 의과대학 성형외과학교실) ;
  • 이종인 (가톨릭대학교 의과대학 재활의학과교실) ;
  • 한기택 (가톨릭대학교 의과대학 성형외과학교실)
  • Jun, Young Joon (Department of Plastic and Reconstructive Surgery, The Catholic University of Korea, College of Medicine) ;
  • Rhie, Jong Won (Department of Plastic and Reconstructive Surgery, The Catholic University of Korea, College of Medicine) ;
  • Choi, Yun Seok (Department of Plastic and Reconstructive Surgery, The Catholic University of Korea, College of Medicine) ;
  • Kim, Young Jin (Department of Plastic and Reconstructive Surgery, The Catholic University of Korea, College of Medicine) ;
  • Kim, Sung Eun (Department of Plastic and Reconstructive Surgery, The Catholic University of Korea, College of Medicine) ;
  • Lee, Jong In (Department of Rehabilitation Medicine, The Catholic University of Korea) ;
  • Han, Ki Taik (Department of Plastic and Reconstructive Surgery, The Catholic University of Korea, College of Medicine)
  • 투고 : 2005.11.25
  • 발행 : 2006.03.10

초록

Using adipose derived stem cells(ASCs), neurogenic differentiation was induced in a mono layered culture medium containing neuronal induction agents. Cells differentiated to the neuronal cells were observed with a inverted microscope and immunofluorecent study. We made a 15 mm long defect in the sciatic nerve of 14 rats and connected a silicone tube to the defect. Then, we mixed neuronal progenitor cells differentiated from ASCs with collagen gel and grafted them to a group of rats(experimental group) and grafted only collagen gel into another group(control group). In 4 and 8 weeks after the graft, histological observation was made. According to the result, the number and diameter of myelinated axons were significantly increased in the experimental group. In addition, the nerve conduction velocity was improved more in the experimental group and neovascularity also increased. Moreover, reaction with S100 and p75 was observed in regenerated nerves in the experimental group, suggesting that the grafted cells were differentiated into supportive cells such as Schwann's cells. In conclusion, this research proved that ASCs can multiply and differentiate into neuronal cells. If they are grafted into nerve defects, the grafted cells are differ entiated into supportive cells such as Schwann's cells and thus contribute to nerve regeneration. Accordingly, the use of adipose tissue obtained easily without the limitation of donor site can be greatly helpful in treating peripheral nerve defects.

키워드

참고문헌

  1. Bryan DJ, Wang KK, Chakalis-Haley DP: Effect of Schwann cells in the enhancement of peripheral-nerve regeneration. J Reconstr Microsurg 12: 439, 1996 https://doi.org/10.1055/s-2007-1006616
  2. Temple S: Division and differentiation of isolated CNS blast cells in microculture. Nature 340: 471, 1989 https://doi.org/10.1038/340471a0
  3. Davis AA, Temple S: A self-renewing multipotential stem cell in embryonic rat cerebral cortex. Nature 372: 263, 1994 https://doi.org/10.1038/372263a0
  4. Svendsen CN, Caldwell MA, Shen J, ter Borg MG, Rosser AE, Tyers P, Karmiol S, Dunnett SB: Long-term survival of human central nervous system progenitor cells transplanted into a rat model of parkinson's disease. Exp Neurol 148: 135, 1997 https://doi.org/10.1006/exnr.1997.6634
  5. McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, Gottlieb DI, Choi DW: Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 5: 1410, 1999 https://doi.org/10.1038/70986
  6. Park Kl: Transplantation of neural stem cells: cellular and gene therapy for hypoxic-ischemic brain injury. Yonsei Med J 41: 825, 2000 https://doi.org/10.3349/ymj.2000.41.6.825
  7. Hintzen RQ: Stem cell transplantation in multiple sclerosis; multiple choices and multiple challenges. Mult Scler 8: 155, 2002 https://doi.org/10.1191/1352458502ms789oa
  8. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH: Human adipose tissue is a source of multi potent stem cells. Mol Bioi Cell 13: 4279, 2002 https://doi.org/10.1091/mbc.E02-02-0105
  9. Murakami T, Fujimoto Y, Yasunaga Y, Ishida 0, Tanaka N, Ikuta Y, Ochi M: Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair. Brain Res 974: 17, 2003 https://doi.org/10.1016/S0006-8993(03)02539-3
  10. Bunge MB, Bunge RP, Kleitman N, Dean AC: Role of peripheral nerve extracellular matrix in Schwann cell function and in neurite regeneration. Dev Neurosci 11: 348, 1989 https://doi.org/10.1159/000111911
  11. Diener PS, Bregman BS: Fetal spinal cord transplants support the development of target reaching and coordinated postural adjustments after neonatal cervical spinal cord injury. J Neurosci 18: 763, 1998
  12. Windrem MS, Roy NS, Wang J, Nunes M, Benraiss A, Goodman R, McKhann GM 2nd, Goldman SA: Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain. J Neurosci Res 69: 966, 2002 https://doi.org/10.1002/jnr.10397
  13. Hurelbrink CB, Armstrong RJ, Dunnett SB, Rosser AE, Barker RA: Neural cells from primary human striatal xenografts migrate extensively in the adult rat CNS. Eur J Neurosci 15: 1255, 2002 https://doi.org/10.1046/j.1460-9568.2002.01959.x
  14. Kang SK, Jun ES, Bae YC, Jung JS: Interactions between human adipose stromal cells and mouse neural stem cells in vitro. Brain Res Dev Brain Res 145: 141, 2003 https://doi.org/10.1016/S0165-3806(03)00224-4
  15. Beyth S, Borovsky Z, Mevorach D, Liebergall M, Gazit Z, Aslan H, Galun E, Rachmilewitz J: Human mesenchymal stem cells alter antigen-presenting cell maturation and induce T-cell unresponsiveness. Blood 105: 2214, 2005 https://doi.org/10.1182/blood-2004-07-2921