Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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A pilot study of neuroprotection with umbilical cord blood cell transplantation for preterm very low birth weight infants

극소 저 출생체중 미숙아에서 자가 제대혈 줄기세포 이식을 통한 신경 손상 방지 연구

  • 채규영 (포천중문의대 소아과학교실) ;
  • 이규형 (포천중문의대 소아과학교실) ;
  • 은소희 (고려대학교 의과대학 소아과학교실) ;
  • 최병민 (고려대학교 의과대학 소아과학교실) ;
  • 은백린 (고려대학교 의과대학 소아과학교실) ;
  • 강훈철 (인제대학교 의과대학 소아과학교실) ;
  • 최명재 (인제대학교 의과대학 소아과학교실) ;
  • 김남근 (포천중문의대 임상의학연구소) ;
  • 오도연 (포천중문의대 임상의학연구소)
  • Received : 2007.07.17
  • Accepted : 2007.07.30
  • Published : 2007.09.15
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Abstract

Purpose : Preterm very low birth weight infant have high rate of adverse neurodevelopmental sequale. Recently, there have been lots of reports that human umbilical cord blood transplantation ameliorates functional deficits in animal models as hypoxic ischemic injury. This pilot study was undertaken to determine the clinical efficacy and safety of autologous umbilical cord blood cell transplantation for preventing neurodevelopmental sequale in perterm VLBW. Methods : Subjects were 26 preterm infants whose birth weight are less than 1,500 g and delivered under the intrauterine period 34 weeks. Autologous umbilical mononuclear cells (about $5.87{\times}10^7/kg$) were injected to neonate via the umbilical vein on the postnatal 24-48 hour. The therapeutic efficacy was assessed by numbers of nucleated RBC, urinary uric acid/creatinine ratio, concentration of neuron specific enolase (NSE), interleukin 6 (IL6), interleukin-$1{\beta}$ ($IL-1{\beta}$), and glial cell derived neurotrophic factor (GDNF) in serum and cerebrospinal fluid on day 1 and 7. Results : There were no significant differences in the numbers of the nucleated RBC, urinary uric acid/creatinine ratio, concentration of creatine kinase between the transplanted infants and controls. But the nucleated RBC is more likely to be rapidly discharged in the transplanted group. In the transplanted group, the concentrations of IL6, $IL-1{\beta}$, and GDNF were no significant difference between day 1 and 7, although GDNF seemed to be elevated. Serum NSE concentration was significantly elevated after transplantation, but not in CSF. Conclusion : It is suggested that autologous umbilical cord blood transplantation in preterm very low birth weight infant is safe to apply clinical practice. Long term follow up study should be needed to evaluate the potential therapeutic effect of umbilical cord blood transplantation for neuroprotection.

목 적 : 제대혈액 내 줄기세포 자가 이식이 극소저출생 미숙아의 신경학적 손상을 방지할 수 있는지 알아보고자 하였다. 방 법 : 출생체중 1,500 g 미만, 제태연령 32주 이하인 미숙아 26명을 대상으로 하였다. 환자의 제대혈에서 단핵구만 분리한 후 생후 24-48시간 사이에 단핵구로서 평균 $5.87{\times}10^7/kg$개를 정맥주사 하였다. 평가 변수들로서는 저산소성-허혈성 뇌증의 예측 지표로 사용되는 유핵 적혈구수, 소변내의 uric acid/creatinine 비와 NSE, IL-6, $IL-1{\beta}$ 등과 신경세포 보호 작용이 있는 것으로 알려진 GDNF의 농도를 혈청 및 뇌척수액에서 측정하였다. 임상적으로는 생후 1개월의 두위 증가 정도와 함께 뇌 병변, 기관지폐이형성증, 미숙아 망막증, 괴사성 장염 등의 발생 정도를 평가하였다. 결 과 : 1) 소변내 uric acid/ceartinine 비는 줄기세포 자가 이식군과 대조군 사이에 차이가 없었으나 유핵 적혈구수의 감소는 줄기세포 이식군에서 빠르게 감소하는 경향을 보였다. 2) 제대혈 자가 줄기 이식 전후에 시행한 혈청 NSE와 IL-6는 생후 제 7일에 의미 있게 감소하였으나 뇌척수액에서는 통계학적인 의미를 보이지 않았다. 혈청 $IL-1{\beta}$는 생후 제 7일에 감소하고, 혈청 GDNF 농도는 줄기세포 이식 후 증가하는 경향을 보였으나 모두 통계학적인 의미는 없었고 뇌척수액에서도 차이를 보이지 않았다. 3) 생후 1개월에서의 두위 성장(2 cm 이상)은 줄기세포 이식군에서 11명(46%), 대조군은 3명(27%)이었다. 4) 생후 1개월에서의 뇌병변은 줄기세포 이식군 24명 중 3명에서 뇌실주위 연화증이 발생하였고 그 중 1명은 뇌실확장증을 동반하였으며 대조군에서는 11명 중 2명에서 뇌실주위 백질연화증과 뇌실확장증이 발생하였다. 5) 줄기세포 이식군에서 기관지폐이형성증 및 괴사성 장염이 각각 1명씩 발생하였고 대조군에서는 미숙아 망막증이 2명에서 발생하였다. 6) 줄기세포 이식군에서 신생아호흡곤란 증후군과 연관된 패혈증으로 2명이 사망하였으며 제대혈 줄기세포 자가 이식과는 연관관계가 없었다. 결 론 : 극소 저출생체중 미숙아에서 제대혈 자가이식술은 윤리적인 문제없이 쉽게 시행할 수 있는 안전하고 실용적인 신경손상 예방 및 치료법으로 기대된다. 향후 장기적인 신경학적 추적 검사 및 비침습적이며 정교한 평가 변수 확립이 필요하다.

Keywords

Acknowledgement

Supported by : 한국학술진흥재단

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