줄기세포 치료의 허와 실

오일환 대한의사협회 2013 대한의사협회지 Vol.56 No.10

Stem cell therapy has been taken as a highly promising area of future medicine due to its potential for providing new therapeutic modalities for debilitating, incurable diseases. In addition, stem cell therapy holds promise for its great industrial value due to the rapid growth of the market size. Recently, various types of stem cells such as induced pluripotent stem cells are being developed based on the conceptual revolution with regard to cell fate decisions. However, so far, most stem cell therapies have been performed using tissue-specific adult stem cells. Nevertheless, except for a few cases of stem cells such as hematopoietic stem cells that can regenerate hematopoietic tissue, a large proportion of stem cells, especially mesenchymal stromal cells, primarily work through paracrine functioning. The short life span of the injected stem cells and their paracrine mode of action pose a limitation to the maximum therapeutic efficacy that can be achieved from the current stem cell therapy model, warranting further research and development to enhance their efficacy. Despite the fact that stem cell therapies largely remain in the research stage, the public has expectations of rapid results and even fanaticism, leading to unauthorized stem cell practices and medical tourism. Moreover, the temptation to expedite the industrialization of stem cell therapeutics by simplifying the authorization process could increase the risk of endangering the rights of patients. Thus, stem cell therapy can become a ‘hope’ when society can overcome the stem cell ‘hype’.

Stem Cell-Based Therapies for Liver Diseases: An Overview and Update

Jie Wang,Meiyan Sun,Wei Liu,Yan Li,Miao Li 한국조직공학과 재생의학회 2019 조직공학과 재생의학 Vol.16 No.2

BACKGROUND: Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases. METHODS: In this review, we summarized the updated researches in the field of stem cell-based therapies for liver diseases as well as the current challenges and future expectations for a successful cell-based liver therapy. RESULTS: Several cell types have been investigated for liver regeneration, such as embryonic stem cells, induced pluripotent stem cells, liver stem cells, mesenchymal stem cells, and hematopoietic stem cells. In vitro and in vivo studies have demonstrated that stem cells are promising cell sources for the liver regeneration. CONCLUSION: Stem cell-based therapy could be a promising therapeutic method for patients with end-stage liver disease, which may alleviate the need for liver transplantation in the future.

Stem cell delivery systems inspired by tissue-specific niches

Choi, Y.C.,Choi, J.S.,Woo, C.H.,Cho, Y.W. Elsevier Science Publishers 2014 Journal of controlled release Vol.193 No.-

Since stem cells have the capacity to differentiate into a variety of cell types, stem cell delivery systems (SCDSs) can be effective therapeutic strategies for a multitude of diseases and disorders. For stem cell-based therapy, stem cells are introduced directly (or peripherally) into a target tissue via different delivery systems. Despite initial promising results obtained from preclinical studies, a number of technical hurdles must be overcome for ultimate clinical utility of stem cells. A key aspect of SCDSs is how to create local environments, called stem cell niches, for improvement of survival and engraftment as well as the fate of transplanted stem cells. The stem cell niches encompassing a wide range of biochemical, biophysical, and biomechanical cues play a guidance role to modulate stem cell behaviors such as adhesion, proliferation, and differentiation. Recent studies have tried to decipher the complex interplay between stem cells and niches, and thereafter to engineer SCDS, mimicking dynamic stem cell niches encompassing a wide range of biochemical, biophysical, and biomechanical cues. Here, we discuss the biological role of stem cell niches and highlight recent progress in SCDS to mimic stem cell niches, particularly focusing on important biomaterial properties for modulating stem cell fate.

줄기 세포 분야의 유전자 치료 연구 동향

오유경,정형민 한국약제학회 2002 Journal of Pharmaceutical Investigation Vol.32 No.2

Recently, stem cell-mediated gene therapy is emerging as a novel therapeutic approach. For the successful gene modification of stem cells, the development of a suitable gene transfer technique needs to be preceded. This review focuses on the various gene transfer techniques based on nonviral and viral vectors, and physical methods. The advantages and disadvantages of each gene transfer method are compared, and the general properties of these vectors are discussed in relation to the gene transfer in stem cell research. This review also highlights the therapeutic application of stem cell-mediated gene therapy. The choice of gene transfer vectors may vary depending on the type of the stem cells and the target of stem cell therapy. Of various gene transfer methods, viral vector-based gene therapy has been emphasized due to the higher transfection efficiency. The current status and up-to-date findings of stem cell-mediated gene therapy are discussed in the viewpoint of the various targets of stem cell therapy such as the modification of stem cell potency, the acceleration of regeneration process and the formation of expressional organization.

줄기세포 유래 세포치료제의 개발 전략 및 임상화 과정

조명수 ( Myung Soo Cho ),유대훈 ( Dae Hoon Yoo ),송슬애 ( Seul Ae Song ),최영민 ( Young Min Choi ) 서울대학교 인구의학연구소 2012 人口醫學硏究論集 Vol.25 No.-

Stem cells are good cell sources for cell replacement therapy of degenerative or incurable disorders. However, there are some limitations such as immune response, differentiation efficiency, safety and ethical issues for clinical application. These barriers must be considered thoroughly from starting point of the investigational study. For clinical application and commercialization of stem cell-derived cell therapy products, strict preparation is required for formal approval of regulatory body at each stage of the clinical process. This preparation process can be another barrier and challenge to the researcher or developer related to stem cell study. However, These challenges will become increasingly important to stem cell research as clinical translation progresses and helpful for birth of authentic novel cell therapy products. In this brief review, we will suggest more effective strategy of the stem cell research and development and introduce the clinical process for cell therapy products briefly.

배아줄기세포의 임상적용

정형민 대한의사협회 2011 대한의사협회지 Vol.54 No.5

Recent advances in stem cell biology, including the development of optimized cell typespecific culture systems, and the broader understandings of biochemical and molecular signals involved in cell self-renewal and differentiation have brought cell-based therapy closer to practical application. As of now, at least 250 adult stem cell therapies are being used or tested in clinical situations. Stem cells have two important properties that distinguish them from other types of cells; they can both proliferate without changing their phenotypes indefinitely, and they also can differentiate into one or more new kinds of cells depending on their culture conditions. Thus, stem cell therapy could be most effective for treating the diseases that are marked by the loss of cells. The typical examples are Parkinson s disease, Alzheimer’s disease, diabetes, heart failure, blindness, spinal cord injury, and stroke. Additionally, stem cell derivatives can be used in drug discovery as well. In the last decade, various types of stem cells have been identified from preimplantation stage embryos, fetuses, placentas, and adult tissues. Moreover, it is now almost a common practice to produce induced pluripotent stem (iPS) cells from various adult somatic cells using only a few defined factors. Thus, it is feasible that patient-specific stem cells will be generated with less controversy in the near future. However, human embryonic stem (ES) cells firmly remain the gold standard because of their greatest potential to become any type of cell in the body. The vast knowledge obtained from human ES cell research in the past decade has made cell-based therapy more promising than ever. Even the recent establishment of iPS cell technology is the culmination of human ES cells research. In our laboratory, interesting human cardiovascular cells including endothelial precursor cells and beating myocardiac cells, artificial blood cells, and retinal pigment epithelial cells were successfully differentiated and their therapeutic potential was confirmed after cell transplantation into animal models. Thus, here, the current research status of human embryonic stem cell-based therapy will be introduced and the future directions of stem cell applications in clinical trials will be discussed.

신경줄기세포의 냉동보관법 확립

권광원(Kwang Won Kwon),김미란(Mi Ran Kim),서해영(Haeyoung Suh-Kim),이영돈(Young Don Lee),김성수(Sung Soo Kim) 대한해부학회 2004 Anatomy & Cell Biology Vol.37 No.6

신경줄기세포(neural stem cells)는 신경세포와 신경아교세포를 형성할 수 있는 능력을 가진 세포로서 발생중인 중추신경계뿐만 아니라 성인 뇌조직의 제한된 부위에서도 발견된다. 본 연구에서는 사람 신경줄기세포의 장기간 보존을 위하여 냉동보관 방법을 확립하였다. 또한 냉동보관된 태아 뇌조직으로부터 신경줄기세포를 분리, 배양할 수 있는 가능성을 조사하였다. 우선 신경줄기세포의 표지자로 알려진 nestin의 발현과 함께 green fluorescence protein (GFP)을 발현하는 형질전환 생쥐를 이용하여 신경구의 형태로 증식된 세포가 신경줄기세포임을 GFP 발현을 통해 확인하였다. 태아의 신경줄기세포는 신경구에서 nestin의 발현을 통해 확인하였고, 분화조건에서 신경세포, 별아교세포, 희소돌기아교세포로 분화하는 것으로 미루어 이들이 다분화능을 유지하고 있음을 확인하였다. 신경구를 냉동보관하고 해동시킨 후 다시 증식시켜 얻은 신경구의 분화능력은 냉동 전의 신경구와 차이를 나타내지 않았다. 또 임신 10~15주의 태아의 대뇌조직을 잘게 부수어 신경구와 동일한 방법으로 냉동보관한 후 이를 해동시켜 신경구의 형성을 유도한 경우에도 신경세포와 별아교세포로의 분화능력이 유지됨을 관찰하였다. 이는 조직에 남아있던 신경줄기세포가 생존하여 증식하였기 때문으로 추정된다. 본 연구의 결과는 뇌조직이나 대량 배양된 신경구를 장기간 냉동보관하여 필요한 시기에 해동, 배양하여 신경줄기세포의 이식에 사용할 수 있다는 가능성을 제시하고 있다. Neural stem cells are multipotent stem cells that can differentiate into neurons and glial cells. Neural stem cells are found in not only developing nervous system but some restricted regions in adult brain. Here, we presented an effective method that allows a long-term preservation of neural stem cells without losing multipotency. First, we isolated neural stem cells from the developing forebrain of nestin-EGFP transgenic mice carrying green fluorescence protein (GFP) driven by nestin promoter and enhancer. Primary neurospheres isolated from these mice highly expressed GFP. The expression of GFP in neurospheres was sustained for several passages. In order to investigate the effect of freezing on the stem cell properties, we cryopreserved the primary neurospheres for 2 wks in liquid nitrogen. GFP expression pattern as well as differentiation potential of the secondary neurosphere formed after cryopreservation were not that different from those of the primary neurosphere formed before cryopreservation. When the same cryopreservation method was applied to neural stem cells isolated from human fetal brain (gestation 13~15 wks), the expression of nestin, a stem cell marker, and differentiation patterns were not changed after cryopreservation. We also performed isolation of neural stem cells from long-term cryopreserved human fetal brain tissues. The neurospheres were successfully formed and showed similar differention properties with neurospheres isolated from fresh brain tissue. In addition, we demonstrated multipotentiality of neural stem cells was not changed with the duration of cryopreservation of brain tissue, suggesting the self renewality and multipotentiality of neural stem cells were not affected by long-term cryopreservation, The present results provide an useful information for the development of stem cell expansion which is essential factor in clinical application of stem cells.

줄기세포기반치료에 대한 미국의 규제 경향 고찰

박수헌(Park, Soo Hun) 이화여자대학교 생명의료법연구소 2016 생명윤리정책연구 Vol.9 No.3

줄기세포기반치료는 줄기세포에 기반을 둔 생물학적 제품을 사용하여 질병을 치료 및 예방하는 것을 말한다. 줄기세포기반치료에 대해서는 환자에의 신속한 적용과 안전성 보장 간의 형량으로 인해 미국 FDA의 전통적 규제의 적용에 대해서는 찬반 의견이 있다. 연방법원의 입장은 줄기세포기반치료는 생물의약품에 해당하기 때문에 FDA의 전통적 규제의 적용 대상이 된다는 것이지만, 자가줄기세포치료를 FDA의 품목허가를 받지 않은 채 환자들에게 적용하고 있는 영리 클릭닉들이 사실상 존재하고 그에 대한 FDA 규제의 불이행이 또한 존재한다. 이는 줄기세포기반치료의 안전성과 유효성을 확보해야 하는 동시에 심각한 상태나 생명을 위협하는 질환을 가진 환자들에게 신속한 적용도 이루어져야 한다는 공익실현이 혼재되어 있기 때문이다. 이를 해결하기 위해 FDA는 입법을 통하여 특정 상황의 경우에는 전통적 품목허가 절차를 모두 거치지 않더라도 환자들에게 신속하게 적용할 수 있는 신속 프로그램을 오래 전부터 마련하여 시행해 오고 있다. 신속처리, 혁신치료지정, 신속승인은 최소한 임상 2상 종료 후 환자에의 적용 여부가 결정되고 확장된 접근 또는 동정적 사용은 생명이 얼마 남지 않은 말기환자에게 임상 1상을 마친 시험약에 대해 온정적으로 적용될 수 있다. 주 차원에서 인 정되고 있는 시험할 권리법도 임상 1상을 마친 줄기세포기반치료에 대해 적용할수 있도록 한다. 미국의 경우 이러한 신속 프로그램의 마련과 운영이 모두 법률차원에서 이루어지고 있다. 우리의 경우, 대법원이 줄기세포치료를 의약품이라 고 결정하였고 세포치료제도 생물의약품으로 식품의약품안전처의 품목허가를 받아야 환자에게 적용될 수 있다는 입장이다. 임상 3상을 거치지 않고 임상 2상의 자료만으로 품목허가를 해주는 신속심사허가제도도 인정되고 있다. 그렇지만 법 률 차원에서 이들을 규정하고 있지는 않다. 다만, 약사법에서 확장적 접근 또는 동정적 사용만을 규정해 두고 있다. 우리도 법률 차원에서 신속 프로그램을 마련하여 제약사와 환자의 이익을 모두 보장해 줄 수 있는 제도를 마련해야 할 것이다. Stem cell-based therapy is a method using biological products based on stem cell in order to treat and prevent diseases. When FDA tries to apply its traditional regulations of drug market approval to the stem cell-based therapy, there’re different views on it according to the unique characteristics of stem cell-based therapy itself. The balancing test between expedited application to the patients and securing safety for them should be conducted properly. Even though the federal courts concluded that stem cell-based therapy should be the subject of FDA’s traditional regulation on drug market approval, the profit clinics that are conducting autologous stem cell therapy without getting market approval from FDA are increasing and FDA does not execute its regulatory power on them. This is because the commingling of public interest for expedited application to the serious condition or life threatening disease patients and securing safety and efficacy of stem cellbased therapy. To resolve these issues, FDA have conducted expedited programs for long time without going through all the procedures that the traditional FDA market approval required. The use of accelerated approval, fast track, breakthrough therapy designation is decided after clinical trial phase II is completed. The use of expanded access or compassionate use can be decided to the terminally ill patients after clinical trial phase I is completed. The right to try laws in the State level can also decide the use of stem cell-based therapy after clinical trial phase I is completed. All the expedited programs in the U.S. are administered in the level of statutes. In Korea, the Supreme Court concluded that stem cell-based therapy is drug and can be applied to the patients after MFDS’s traditional drug market permission. The same MFDS’s traditional drug market permission is required for cell therapy as biologics to the patients. The expedited program like fast track is also allowed. However, all these pathways are provided on the level of agency rules not the level of statutes. However, expanded access or compassionate use is only stipulated in the statute. We should prepare expedited programs like those of the U.S. on the level of statutes to guarantee both the pharmaceuticals and the patients all together.

인간배아줄기세포연구의 민사법적 의미

김민중(KIM Min-Joong) 한국법학원 2008 저스티스 Vol.- No.103

인간배아줄기세포연구에 대한 사회적 논쟁이 뜨겁다. 인간배아줄기세포연구가 척수장애, 파킨슨, 알츠하이머, 뇌졸중, 당뇨와 같은 난치병을 퇴치할 수 있다고 하는 의미에서는 이보다 인류에 더 공헌할 수 있는 일을 찾기 어렵다고 할 수 있다. 그러나 인간배아줄기세포연구가 사회적, 윤리적, 법적으로 아무런 문제점도 없다고 할 수는 없다. 인간배아줄기세포의 연구나 이용과 관련하여 선결하여야 할 과제도 적지 않고, 인간배아줄기세포연구에는 과학적인 문제뿐만 아니라 여러 가지 해결하여야 할 윤리적, 법적 문제가 내포되어 있다는 사실을 부인할 수 없다. 현재 인간배아줄기세포의 연구나 이용에 관한 생명윤리의 문제는 국내에서 뿐만 아니라, 전세계적으로도 대단한 논란이 되고 있다. 또한 인간배아줄기세포연구가 야기하는 문제는 생명윤리의 문제에 국한되지 아니한다. 법적으로도 인간배아줄기세포연구와 관련한 다양한 문제가 제기된다. 인간배아줄기세포연구에 관한 근본적인 법적 문제로서는 인간의 존엄성와 관련한 인권문제가 제기된다. 그리고 예를 들어 인간배아 줄기세포연구를 형법적으로 금지하여야 하는가 하는 형법상의 문제도 제기된다. 역시 인간배아줄기세포연구에서의 법적 문제에 관한 핵심적인 내용의 하나는 인간배아줄기세포연구를 둘러싼 민사법적 과제라고 할 수 있다. 인간배아줄기세포연구와 관련하여 제기되는 민사법적 과제는 매우 다양하리라고 예상되며, 계약법적 문제를 비롯하여 책임법적 문제, 가족법적 문제에까지 민법 전반에 걸쳐 문제가 제기될 수 있다. 우선 인간배아줄기세포연구와 관련하여 다양한 계약관계가 성립할 수 있다. 예를 들어 인간배아줄기세포연구를 위하여는 배아, 특히 난자가 필요하므로, 배아나 난자를 제공받기 위하여는 배아제공자 및 난자 제공자와의 사이에 배아제공계약 또는 난자제공계약이 성립한다. 또한 줄기세포를 난치성 질환을 치료하기 위한 세포치료의 재료로 사용하는 경우에는 환자와의 사이에 첨단의료행위로서의 임상실험이나 줄기세포치료를 실시하기 위한 임상실험계약 또는 의료계약이 성립한다. 인간배아줄기세포연구와 관련한 임상실험을 통하여 피실험자나 제3자가 손해를 입을 수 있다. 만약 줄기세포연구를 적용한 임상실험에서 피실험자나 제3자에게 손해가 발생하면 손해배상책임이 문제되고, 보통 임상실험으로 생긴 손해에 따른 피실험자에 대한 책임은 계약책임이 되고, 제3자에 대한 책임은 불법행위책임으로 된다. The debate over the treatment of human stem cell is new. Ever since human stem cells were first isolated, the possible applications of stem cell research and the moral and legal issues surrounding human stem cell research have created much controversy. Now human stem cell research is a controversial and divisive topic. Research on embryonic stem cells has generated great intrigue in the scientific community. Many medical researchers consider stem cell-based therapies to have the potential of treating a host of human illnesses and yielding a number of medical benefits. However, the embryonic stem cell research raises numerous ethical and legal concerns. The embryonic stem cell research destroys the human embryo. This has generated a storm of debate about if this research can be legally and ethically justified. Human embryonic stem cell is 'master cell', able to develop into almost any cell in the human body. The research with human embryonic stem cells raises complex and sensitive legal questions that should be considered carefully and discussed widely. The civil legal debate surrounding human embryonic stem cell research, will be the focus of this paper.

Bio-inspired polymer scaffolds to potentiate stem cell therapy

조승우 한국공업화학회 2015 한국공업화학회 연구논문 초록집 Vol.2015 No.1

Biomaterials can be applied to engineer stem cell therapy for improved therapeutic efficacy and safety. In this talk, our recent effort using bioinspired materials will be introduced to potentiate stem cell therapy by regulating self-renewal, proliferation, and differentiation of stem cells. Firstly, mussel-inspired surface modification was applied to prepare functional scaffolds and substrates for promoting neuronal and osteogenic differentiation of stem cells. Secondly, bio-inspired superhydrophobic substrates were developed as effective culture platforms to produce highly viable, functional stem cell spheroids with enhanced angiogenic potential. Finally, nanotopographical features mimicking aligned extracellular matrix were tested to enhance neurogenesis and osteogenesis of stem cells. These approaches for stem cell engineering combined with bio-inspired materials can potentiate stem cell therapy for the treatment of neurodegenerative diseases and orthopedic injuries.