제대혈 관리 및 연구에 관한 법률의 검토

이정현(Lee-Jeong Hyun) 충북대학교 법학연구소 2010 과학기술과 법 Vol.1 No.1

Umbilical cord blood is blood that is separated from the umbilical cord and placenta connected to a mother's body when the new born is detached from the mother‘s body at childbirth. Umbilical cord blood contains hematopoietic progenitor cells and stem cells. In the past, umbilical cord blood was physiologically inevitably separated from a human body and discarded with the umbilical cord and placenta and it was not a matter of concern. However, as biomedical technologies have been developed, it has become possible to freeze and keep umbilical cord blood and then defrost it to use it for patients' treatment. In Korea, since Catholic Hematopoietic Stem Cell Bank was instituted in 1996, umbilical cord blood banks have been established and operated mainly by university-affiliated hospitals including Samsung Medical Center in 1997, and Severance Hospital in 1998, and these days many organizations are also operating umbilical cord blood banks as a private corporation. As such banks were not supported by systems, the Ministry of Health and Welfare set umbilical cord blood bank practice standards in August of 2005. The standards aimed at ensuring an adequate level of quality and safety of human umbilical cord blood and contributing to the improvement of national health through standards for the management of human umbilical cord blood. Nonetheless, the standards were not legally enforceable, and thus it was required to secure a proper level of safety of human umbilical cord blood and to introduce laws regarding the management of umbilical cord blood including the collection, examination, safekeeping and supply of umbilical cord blood. The Umbilical Cord Blood Management and Research Act was established on March 17, 2010 and the law will become effective from July 1, 2011. On the below, the enactment process and main details of the Umbilical Cord Blood Management and Research Act will be addressed and the problems underlying in the law examined.

Umbilical Cord Blood Transplantation

Ahn, Hyo Seop,Shin, Hee Young The Korean Association of Immunobiologists 2003 Immune Network Vol.3 No.2

The number of umbilical cord blood transplantation is increasing worldwide as it has expanded the ability of the transplantaion community to meet the growing needs of their patients. Clinical data over the last decade show promising results in transplantation using both related as well as unrelated cord bloods. Cord blood banks are essential for the clinical use for transplantation and are now established around the world with the major efforts to standardize banking in collection, processing and distribution of cord blood for providing the highest quality stem cells for the patients. In Korea, Medipost, Histostem and some regional cord blood banks were established some years ago and collected thousands of cord blood for public but it had some limitations and was not expanded as the cord blood transplantation was not covered by medical insurance. Recently with the change in the policy of medical insurance to cover the cord blood transplantation, several venture companies are showing great interests in cord blood banking and trying to establish private cord blood banks in Korea. This review article discusses the current status of cord blood transplantaion and also the clincial use of stem cells from cord blood.

제대혈 관리 및 연구에 관한 법제와 개선방안

정연덕(Yeun Dek Chung) 중앙법학회 2010 中央法學 Vol.12 No.4

The purpose of this study is to develop legal standards in the field of management of umbilical cord blood. Umbilical cord blood consist of hemopoietic progenitor cell and stem cell. Recently doctors and scientist discovers many usage of cord blood. Cord Blood Act deals with cord blood transplantation, private cord blood bank and public cord blood bank. KONOS (Korean Network for Organ Sharing) is the central resource for government-funded technical, and medical related cord blood information. Private cord blood banks and public cord blood bank have invested lots of resource in gaining cord blood and related information. However, outcome of these information does not spread to patient. Thus Cord Blood Act not only regulate but also promote development of this Cord blood industry. After this enactment, the public will have benefit in cancer therapy. This paper aims to suggest a standard to deal with balance of Private Cord Blood Bank and Public Cord Blood Bank. It also deal with right of patient in using the information provide from KONOS. The public would be served by having ready access with cord blood information. Finally, it will address the need to consider issues for regulation of Cord Blood Business and distribution of information to develop a legal framework to deal with this problem.

통영지역 임산부의 생선섭취가 제대혈의 수은 농도에 미치는 영향

장철원,최종덕,김상현 한국식품위생안전성학회 2012 한국식품위생안전성학회지 Vol.27 No.1

Fish contain both the neurotoxin methyl mercury (MeHg) and nutrients important for brain development. The developing brain appears to be most sensitive to MeHg toxicity and mothers who consume fish during pregnancy expose their fetus prenatally. Although brain development is most dramatic during fetal life, it continues for years postnatally and additional exposure can occur when a mother breast feeds or the child consumes fish. This raises the possibility that MeHg might influence brain. We evaluated the relationship between fish consumption and mercury exposure levels in umbilical cord blood of the pregnant women of the city of Tongyeong city, Korea. A total of 159 pregnant women residing in the city of Tongyeong, Korea were recruited for the study between October 2010and March 2011. Fish consumption was evaluated using food frequency questionnaires including detailed questions on fish consumption. We used ANOVA to estimated the particular relevance between the frequency of fish consumption and the umbilical cord blood mercury concentration, and other various factors. The average mean concentration of mercury levels in umbilical cord blood of pregnant women who participated in our study were 2.69 ± 2.50 ppb,ranging from 0.01 to 14.80 ppb. The mean concentration of umbilical cord blood mercury exposure was lower than the level recommended by WHO (5.0 ppb), but the mercury exposure level exceeded the WHO recommended in 17(10.7%) cases of umbilical cord blood. Mercury levels in cord blood of pregnant women were 2.04 ± 2.00 ppb, ranging from 0 to 8.00 ppb in below 29 years old and 3.18 ± 2.74 ppb, ranging from 0.01 to 14.80 ppb in more 30 years old. In this study, there was a significant difference for the frequency of eating fish between the groups (p < 0.01). The level of the groups that ate fish 3 to more times per week (4.15 ± 4.02 ppb) was significant higher as compared with the level of other groups that ate fish 1 to times per week (2.63 ± 2.22 ppb) and none per week (1.06 ± 1.44 ppb),respectively. We found that the mercury concentration of umbilical cord blood associate with fish consumption and this was statistically significant and this fact revels that fish consumption is positively related to mercury levels in the umbilical cord blood. We need systematic and periodic research on the general population to prevent mercury poisoning,which can be cause by low-level mercury exposure from dietary intake such as chronic fish consumption

Isolation and characterization of canine umbilical cord blood-derived mesenchymal stem cells

Min-Soo Seo,Yun-Hyeok Jeong,박정란,박상범,Kyoung-Hwan Rho,김형식,유경록,Seung-Hee Lee,Ji-Won Jung,이영순,Kyung-Sun Kang 대한수의학회 2009 JOURNAL OF VETERINARY SCIENCE Vol.10 No.3

Human umbilical cord blood-derived mesenchymal stem cells (MSCs) are known to possess the potential for multiple differentiations abilities in vitro and in vivo. In canine system, studying stem cell therapy is important, but so far, stem cells from canine were not identified and characterized. In this study, we successfully isolated and characterized MSCs from the canine umbilical cord and its fetal blood. Canine MSCs (cMSCs) were grown in medium containing low glucose DMEM with 20% FBS. The cMSCs have stem cells expression patterns which are concerned with MSCs surface markers by fluorescence- activated cell sorter analysis. The cMSCs had multipotent abilities. In the neuronal differentiation study, the cMSCs expressed the neuronal markers glial fibrillary acidic protein (GFAP), neuronal class III β tubulin (Tuj-1), neurofilament M (NF160) in the basal culture media. After neuronal differentiation, the cMSCs expressed the neuronal markers Nestin, GFAP, Tuj-1, microtubuleassociated protein 2, NF160. In the osteogenic & chondrogenic differentiation studies, cMSCs were stained with alizarin red and toluidine blue staining, respectively. With osteogenic differentiation, the cMSCs presented osteoblastic differentiation genes by RT-PCR. This finding also suggests that cMSCs might have the ability to differentiate multipotentially. It was concluded that isolated MSCs from canine cord blood have multipotential differentiation abilities. Therefore, it is suggested that cMSCs may represent a be a good model system for stem cell biology and could be useful as a therapeutic modality for canine incurable or intractable diseases, including spinal cord injuries in future regenerative medicine studies. Human umbilical cord blood-derived mesenchymal stem cells (MSCs) are known to possess the potential for multiple differentiations abilities in vitro and in vivo. In canine system, studying stem cell therapy is important, but so far, stem cells from canine were not identified and characterized. In this study, we successfully isolated and characterized MSCs from the canine umbilical cord and its fetal blood. Canine MSCs (cMSCs) were grown in medium containing low glucose DMEM with 20% FBS. The cMSCs have stem cells expression patterns which are concerned with MSCs surface markers by fluorescence- activated cell sorter analysis. The cMSC s had multipotent abilities. In the neuronal differentiation study, the cMSCs expressed the neuronal markers glial fibrillary acidic protein (GFAP), neuronal class III β tubulin (Tuj-1), neurofilament M (NF160) in the basal culture media. After neuronal differentiation, the cMSCs expressed the neuronal markers Nestin, GFAP, Tuj-1, microtubuleassociated protein 2, NF160. In the osteogenic & chondrogenic differentiation studies, cMSCs were stained with alizarin red and toluidine blue staining, respectively. With osteogenic differentiation, the cMSCs presented osteoblastic differentiation genes by RT-PCR. This finding also suggests that cMSCs might have the ability to differentiate multipotentially. It was concluded that isolated MSCs from canine cord blood have multipotential differentiation abilities. Therefore, it is suggested that cMSCs may represent a be a good model system for stem cell biology and could be useful as a therapeutic modality for canine incurable or intractable diseases, including spinal cord injuries in future regenerative medicine studies.

인간 제대혈 림프구 체외 증폭시 조절 T 림프구의 변화 양상 및 특징

정의 ( Eui Jung ),김용만 ( Yong Man Kim ),송하영 ( Ha Young Song ),원혜성 ( Hye Sung Won ),김암 ( Ahm Kim ),강병문 ( Byung Moon Kang ) 대한산부인과학회 2006 Obstetrics & Gynecology Science Vol.49 No.10

목적: 조절 T 림프구는 CD4와 CD25를 표현하는 특정 T 림프구를 일컬으며, 자아에 대한 면역반응을 억제하는 역할을 하고 있다. 성인에서도 림프구는 그 자체가 실험실 배양 및 증폭이 까다롭다는 점 때문에 연구에 많은 제한을 받고 있지만 제대혈에서 분리해 낸 림프구, 특히 T 림프구는 적절한 배양 환경만 확립된다면 다양한 기능을 가진 여러 세포로 분화할 수 있고, 자기 복제능이 탁월하다. 본 연구는 만삭 산모와 정상 성인 여성의 말초 혈액, 그리고 제대혈내의 조절 T 림프구의 분포에 차이가 있는지 확인함으로써 산모와 태아간 면역 관용상태에 조절 T 림프구가 관여하고 있는지 알아보고, 또한 제대혈 림프구의 체외 증식이 조절 T 림프구의 분포에 어떤 영향을 미칠 것인가를 확인하여 조절 T 림프구를 다량으로 획득할 수 있는 방법을 확립해 장차 세포치료 등 임상적 이용을 앞당기고자 하였다. 연구 방법: 각각 10명의 비임신 성인 여성과 만삭 산모의 말초혈액 및 제대혈에 항 CD3 항체, 항 CD4 항체, 항 CD25 항체, 항 CD152 항체를 첨가한 후 FACSort flow cytometry를 이용하여 세포 표식자 분석을 시행하였다. 제대혈은 Ficoll-Hypaque 밀도 기울기 원심 분리법으로 단핵구 세포를 분리하여 항 CD3 항체와 IL-2를 이용한 체외증폭을 시행한 후, 배양 제 0, 4, 11, 21일에 세포 표식자 분석과 FoxP3의 발현도를 측정하였다. 또한 MACS(TM) kit를 이용하여 CD25-와 CD25+ T 림프구를 분리하여 CD25+ 림프구의 조절 T 림프구 여부를 FoxP3의 발현을 통해 확인하였다. 결과: 제대혈내의 CD4+CD25++ T 림프구는 정상 성인 여성과 산모의 말초혈액보다 높은 분포를 나타냈으며, 만삭 산모는 비임신 여성보다 CD4+CD25++ T 림프구가 유의하게 적었다 (p<0.05). 제대혈 림프구를 체외 배양했을 때 CD4+CD25++ 그리고 CD152+ T 림프구의 비율은 4일째 현저하게 높아지고 11일째 이후로 감소하는 소견을 보였고 (p<0.05), 이는 FoxP3의 발현 정도와도 일치한 결과를 보였다. 분리된 CD4+CD25+ T 림프구는 CD4+CD25- T 림프구에 비해 FoxP3 발현량이 의미있게 높았다 (p<0.05). 결론: 제대혈은 성인의 말초혈액보다 CD4+CD25++ 조절 T 림프구의 비율이 높으며, 체외 증폭하였을 때 조절 T 림프구의 비율이 4일째까지 증가하다가 이후로 감소되는 소견을 보인다. 이 결과는 향후 조절 T 림프구의 임상적 이용에 유용한 자료로 사용될 수 있다고 사료된다. Objective: Regulatory T cells, which expressing CD4 and CD25, have a crucial role in suppressing immune systems to self-antigens and preventing autoimmune diseases. This study aims to evaluate the role of regulatory T cells in maternal tolerance to the fetus by comparing the proportion of regulatory T cells in peripheral blood of pregnant and non-pregnant women with those in umbilical cord blood. Also we analyze the changes of proportions of regulatory T cells of umbilical cord blood according to ex vivo expansion. Methods: An immunophenotypic study on 10 peripheral blood of pregnant and non-pregnant women and 10 cord blood was performed by means of FACSort flow cytometry using anti-CD4, anti-CD25 and anti-CD152 antibodies. Fresh cord blood mononuclear cells (MNCs) were isolated by Ficoll-Hypaque density centrifugation. The MNCs were cultured in anti-CD3 Ab-coated flasks for 4 days. The cells were then transferred to non-coated flasks with IL-2 175 U/mL and were cultured for another 17 days. The expression of CD4, CD25, CD152 and FoxP3 PCR were analyzed in accordance with days in culture. We also performed FoxP3 PCR in isolated CD25+ and CD25- T cells using MACS(TM) kit. Results: Umbilical cord blood had a higher proportion of CD4+CD25++ regulatory T cells than adults, and term-pregnant women had a lower proportion than non-pregnant women (p<0.05). After ex vivo expansion in anti-CD3 Ab coated flask with IL-2, we observed a significantly increased expression of CD4, CD25, CD152 at 4(th) day after culture and decrease thereafter. The result was the same as the expression of FoxP3 PCR. Conclusion: Umbilical cord blood contained a high proportion of CD4+CD25++ regulatory T cells and regulatory T cells increased on culture day 4 and declined thereafter. Umbilical cord blood may serve as a readily available source of regulatory T cells for immunotherapy.

우리나라와 일본의 조혈모세포이식 관련법의 비교검토

송영민(Song, Young-Min) 원광대학교 법학연구소 2021 圓光法學 Vol.37 No.3

조혈모세포는 채취 방식 및 장･단점에 차이가 있지만, 골수･말초혈･제대혈로부터 채취가 가능하다는 기본적인 공통점을 가지고 있다. 조혈모세포이식법과 같은 통합적인 법의 제정은 ① 현행 ｢장기이식법｣ 체계상의 문제점을 해결할 수 있다는 점, ② 골수이식, 제대혈이식, 말초혈이식 등 이들 이식만이 갖는 고유한 기능에 대한 보다 적극적인 연구 및 이용의 활성화가 가능하다는 점, ③ 이들 물질의 통합적 관리시스템의 구축이 가능하다는 점 등의 장점이 있다. 일본은 우리나라에 비해 비교적 입법적 해결이 늦었지만 제대혈이식 성적은 우수한 것으로 알려지고 있다. 이는 조혈모세포이식법상의 골수, 말초혈, 제대혈을 통합하는 조혈모세포이식 데이터 센터(The Japanese Data Center for Hematopoietic Cell Transplantation, JDCHCT)를 중심으로 이식받은 환자 및 기증자의 폭넓은 정보를 수집하고 분석한 결과라고 한다. 반면에 우리나라는 각각의 독립된 법체계로 인하여 골수, 말초혈, 제대혈을 통합하는 정보수집과 제공에 일정한 한계가 있음을 부인할 수 없다. 이러한 이유로 의료계 내부에서도 이들 특별법의 상위법인 조혈모세포법의 제정이 필요하다는 의견이 있다. 더 나아가 최근에는 장기 등 이식에 관한 법률, 인체조직안전 및 관리 등에 관한 법률의 통합에 의해 자원의 관리와 배분의 효율성을 높이자는 움직임도 있다. 의생명과학의 발달로 인하여 인체의 다양한 부분을 치료나 연구의 목적으로 사용할 가능성은 점점 더 증가하고 있다. 입법 단계에서는 현재 발생한 문제를 해결하기 위한 단편적 측면이 강조되는 경우가 있다. 그러나 또 다른 한편으로는 장래에 발생가능한 법률문제 해결을 위한 법의 예측기능을 강조해야 하는 경우도 있다. 의생명과학기술의 비약적인 발전은 사전에 예측할 수 없는 법률문제를 발생시킬 수도 있지만 적어도 예측가능한 부분에 대해서는 사전예방적 차원에서 입법작업시에 검토되어야 할 것이다. 그렇다면 이번 기회에 골수, 말초혈, 제대혈을 통합하는 이른바 조혈모세포이식법을 제정하여 조혈모세포의 통합관리와 배분을 기하고 의료기술의 발전에 따른 법의 탄력적인 집행이 가능하게 할 필요가 있다. Although there are different collection methods, advantages and disadvantages in hematopoietic stem cell, it has basic common point to be able to collect from bone marrow, peripheral blood and umbilical cord blood. There are several advantages through integrative legislation like hematopoietic stem cell act, they are as follows. ① it can solve the problem about current ｢Internal Organ Transplant Act｣, ② it can activate more active research and use on unique function of bone marrow transplantation, umbilical cord blood transplantation and peripheral blood transplantation, ③ it can build integrative management system. Japan was late to solve legislatively comparing Korea, however the results of umbilical cord blood transplantation was excellent. This is the result of collecting and analysing wide-ranging information about donee and donor focusing on JDCHCT(the Japanese data center for hematopoietic cell transplantation) integrating bone marrow, peripheral blood, umbilical cord blood. On the other hand, Korea has certain limit to collect and provide the information integrating bone marrow, peripheral blood, umbilical cord blood due to each independent legal system. Thus, there is an opinion to legislate hematopoietic stem cell act, a higher act of this special act, in the medical world. Furthermore, there is a move to enhance efficiency of management and distribution of resource through integrating internal organs, etc. transplant act, and safety, management, etc. of human tissue act. The possibility to use various parts of human body for research and remedy is more and more increasing by development of biomedical science. Fragmentary side would be highlighted to solve current problems in legislative steps, but on the other hand, legal predictive function should be highlighted to solve possible legal problems in the future. Rapid development of biomedical science would generate unpredictable legal problems, but, at least, predictable parts should be examined as a preventive dimension in the legislative work. Therefore, it is necessary to enforce flexible law through integrative management and distribution of hematopoietic stem cell and development of medical technology by legislating so-called hematopoietic stem cell transplantation act that integrates bone marrow, peripheral blood, umbilical cord blood.

산모혈과 제대혈의 혈청 지질치에 영향을 미치는 요인에 대하여

민재희,정규혁,연제덕 한국환경보건학회 1997 한국환경보건학회지 Vol.23 No.3

To investigate the effect of several factors on serum lipids in maternal and infants umbilical cord blood, 111 cases of newborn infants and women delivered of a child who had delivered at hospital located in Chung-Ju city from Feb. 1, 1996 to Aug. 31, 1996 were studied. The gestational ages of cases were 37 to 42 weeks and the average maternal ages were 28.1$\pm$4.25 years old without any other medical or obstetric problems. No relationships between maternal consumption of coffee and maternal serum lipid levels were observed. However, serum total cholesterol and LDL-cholesterol levels in infants umbilical cord were significantly increased in proportion to increasing maternal consumption of coffee. The other factors such as alcohol drinking habits and residency affected maternal serum lipid levels and not serum lipid levels in infants umbilical cord. Delivery frequency showed very little or no effects on serum lipid levels in both maternal blood and infant s umbilical cord blood. In conclusion, maternal consumption of coffee significantly correlated with increasement of serum lipid levels in infants umbilical cord.

Immunohistomorphometric Analysis of Transplanted Umbilical Cord Blood-Derived Mesenchymal Stem Cells and The Resulting Anti-Inflammatory Effects on Nerve Regeneration of Injured Canine Spinal Cord

( Hak Hyun Ryu ),( Ye Eun Byeon ),( Sung Su Park ),( Byung Jea Kang ),( Min Soo Seo ),( Sang Bum Park ),( Wan Hee Kim ),( Kyung Sun Kang ),( Oh Kyeong Kweon ) 한국조직공학·재생의학회 2011 조직공학과 재생의학 Vol.8 No.2

In order to investigate the beneficial mechanism of transplanted canine umbilical cord blood-derived mesenchymal stem cells (UC-MSCs) on spinal cord injury (SCI), we evaluated recovery in a canine SCI model by examining neurological function and nerve regeneration. Recovery was assessed by clinical observation and by examining regenerated nerve cells by immuno-histomorphometric analysis and by assessing anti-inflammation by measuring mRNA expression of inflammation-related cytokines. Extradural compression of the spinal cord in 21 dogs (4.6±0.4 kg, ~2-3 yrs) was performed using a balloon catheter for 12 hours. All of the dogs showed hind limb paralysis after compression. Functional recovery of the hind limbs was evaluated by the Olby score and Revised modified tarlov scale. Experimental dogs were divided into cUCB and control groups. In the cUCB group (n=12), UC-MSCs were infected with a lentivirus-vector labeled GFP gene and injected into the SCI site. In the control group (n=9), only PBS was injected into the SCI site. Seven dogs (control = 3, cUCB = 4) were euthanized and their injured spinal cords were collected at 1, 4 and 8 weeks after transplantation. Nerve regeneration was assessed on longitudinal sections at the epicenter. After transplantation of UC-MSCs, functional improvement up to 5 points of the Olby score and 4 points of Revised modified tarlov scale were observed. Compared to the control group, immuno-histomorphometrical analyses showed that cells labeled with GFAP were significantly reduced and cells labeled with Tuj1 and NF160 were increased in the cUCB group (p < 0.05). In western blot analysis, total gliosis in the cUCB group was reduced by 35% compared to controls and surviving nerve cells in the SCI lesion were increased by more than 50 % compared to controls at 8 weeks after transplantation. However, it must be noted that a small number of nerve cells were derived from the transplanted UC-MSCs. In addition, the expression of COX2, IL1, IL6, TNF and TGF-β, in the cUCB group were down regulated. These findings suggest that improvements of neurological function seen after transplantation of UC-MSCs into injured spinal cord might be due primarily to reduced gliosis by anti-inflammation, increased survival of endogenous nerve cells and enhanced function of survived endogenous nerve cells by engrafted cells.

자가 제대혈장을 이용한 제대혈 T 림프구의 체외 배양

이상수 ( Sang Soo Lee ),손우석 ( Woo Seok Sohn ),박한뫼 ( Han Moie Park ),김용만 ( Young Man Kim ),목정은 ( Jung Eun Mok ) 대한산부인과학회 2005 Obstetrics & Gynecology Science Vol.48 No.3

목적: 본 연구의 목적은 향후 세포 면역치료시 사용할 수 있는 T 림프구를 제대혈로부터 분리하여 체외 배양하는데 필요한 최적 조건을 확립하기 위하여, 기존에 사용하던 FBS와 자가 제대혈장 (autologous cord blood plasma, ACBP), 동종 제대혈장 (homologous cord blood plasma, HCBP)을 각각 T 림프구 체외 배양 배지의 영양공급원으로 사용하여, T 림프구의 증폭, 증폭 전후의 T 림프구의 면역학적 특성 Objective: The objective of this study was to establish a clinically applicable culture system by investigating the use of autologous cord blood plasma (ACBP) instead of fetal bovine serum (FBS) for the ex vivo expansion of umbilical cord blood (UCB) T-ly