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장간막 성체줄기세포는 주위환경의 느낌에 따라 분화
Source: University of Pennsylvania
http://www.eurekalert.org/pub_releases/2006-08/uop-uop082306.php
Adult stem cells are touchy-feely, need environmental clues
24-Aug-2006 Contact: Greg Lester glester@pobox.upenn.edu 215-573-6604
펜실베이니아 대학의 연구에 의하면 어떤 성체줄기세포들은 자신이 위치한 물리환경의 “느낌”에 따라 뼈, 근육, 뉴런 또는 다른 형태의 조직으로 변할 수 있다.
연구팀은 인체의 자연적 재생 메커니즘의 일부로서 골수에 있는 장간막(腸間膜) 줄기세포가 부분적 물리 환경 조건에 따라 다른 형태의 조직으로 변형된다는 것을 발견했다. 심지어 연구자들은 줄기세포가 배양된 겔의 단단함을 바꾸는 것으로 줄기세포를 조작할 수 있었다.
이 논문은 Cell 저널 8월 25일자에 실렸으며, 연구자들은 이 발견이 성체줄기세포에 대한 연구방향을 바꿀 수 있다고 생각한다.
“기본적으로 장간막 줄기세포는 자신이 있는 위치를 느끼고 그 느낌대로 변한다. 이 결과는 질병에 대한 줄기세포의 이용에 대한 기초와 배아 발달에서의 줄기세포 행동의 물리적 초석의 시작이다.”라고 Dennis Discher 교수가 말했다.
줄기세포 연구의 많은 부분이 화학적 미세환경(microenvironment)연구를 이용한다. 이것은 분화과정을 통해 줄기세포를 안내하는 것으로 생각되는 화학적 메신저 신호의 수프로서, 이곳에서 줄기세포가 특정한 세포로 변한다. 펜실베이니아 연구팀은 최초로 물리적 미세환경 또한 분화를 통해 세포를 유도하는데 결정적임을 증명했다. 이번 연구의 제1저자인 Adam Engler 교수에 따르면 두뇌를 흉내낸 미세환경이 세포들을 뉴런이 되는 방향으로 유도하며, 근육을 흉내낸 좀더 뻣뻣한 미세환경은 세포들이 근육세포가 되는 방향으로 유도하며 비교적 단단한 미세환경은 세포들이 뼈가 되는 방향으로 유도한다.
“물리적 환경이 줄기세포의 운명을 제한할 것이라 내가 예견한 반면, 나는 그것이 세포의 운명을 이끄는데 충분할 것이라고는 전혀 생각하지 않았다. 아담교수의 첫 이미지에서 물리 환경만으로 줄기세포가 뉴런 또는 근육 또는 뼈가 되도록 구분 짓는다는 것을 알고는 깜짝 놀랐다.”라고 공동저자 Lee Sweeney 교수가 말했다.
장간막 줄기세포는 주위 사물의 압박감을 통해 환경을 감지한다. 각 세포의 골격에는 근육으로 사용하는 분자 모터를 갖고 있다. 연구자들에 따르면, 줄기세포가 세포의 근육을 움직이는데 필요한 힘의 양이 세포내부의 화학신호를 유발시켜 세포의 분화를 이끈다.
“세포 골격은 우리 근육에서처럼 악틴과 미오신 단백질분자에 의해 만들어진 기계적 압력에 바탕한 모터들을 사용한다. 우리가 미오신을 제거하자, 세포들은 물리환경에 반응하지 않았다.”고 Engler 교수가 말했다.
그러나, 물리적 미세환경은 상처 때문에 또한 질병 때문에도 변화할 수 있으며, 이 점이 이들 줄기세포의 치료이용을 어렵게 한다. 예를 들어 심장 발작 후 심장은 상처가 심해, 줄기세포들이 대체심장근육으로 변해 상처를 치료하는데 효과가 없어 보인다.
“심장 조직은 심장발작 중에 심하게 손상 받을 수 있어 줄기세포들은 미세환경을 심장근육으로 변하는 신호로 인지하지 못한다. 그러나 우리 연구는 심장, 척주 또는 어떤 손상을 입은 환경이든 이식하기 전 실험실에서 치료용 줄기세포를 자극시킬 수 있음을 보여준다.
Source: University of Pennsylvania
http://www.eurekalert.org/pub_releases/2006-08/uop-uop082306.php
Adult stem cells are touchy-feely, need environmental clues
24-Aug-2006 Contact: Greg Lester glester@pobox.upenn.edu 215-573-6604
PHILADELPHIA - A certain type of adult stem cell can turn into bone, muscle, neurons or other types of tissue depending on the "feel" of its physical environment, according to researchers at the University of Pennsylvania.
The researchers discovered that mesenchymal stem cells, which regularly reside in the bone marrow as part of the body's natural regenerative mechanism, depend on physical clues from their local environment in order to transform into different types of tissue. The researchers were even able to manipulate stem cells by changing the firmness of the gel on which they were grown.
The researchers believe that their findings, which appear in the Aug. 25 issue of the journal Cell, could change the way in which people work with stem cells.
"Basically, mesenchymal stem cells feel where they're at and become what they feel," said Dennis Discher, a professor in Penn's School of Engineering and Applied Science. "The results begin to establish a physical basis for both stem-cell use against diseases and for stem-cell behavior in embryonic development,"
Much of the work in stem-cell science has involved the study of the chemical microenvironment, the soup of chemical messenger signals that are generally thought to guide stem cells through the process of differentiation, where relatively "blank" stem cells turn into specific cell types. For the first time, the Penn researchers have proven that the physical microenvironment is also crucial for guiding the cells through differentiation. According to Adam Engler, the first author on the study and a graduate student in the School of Engineering and Applied Science, soft microenvironments, that mimic the brain, guide the cells toward becoming neurons, stiffer microenvironments, that mimic muscle, guide the cells toward becoming muscle cells and comparatively rigid microenvironments guide the cells toward becoming bone.
"While I anticipated that the physical environment might limit the fate of stem cells, I never really thought that it would be sufficient to direct cell fate," said Lee Sweeney, a coauthor of the study and chairman of Physiology in Penn's School of Medicine. "When I saw Adam's first images, I was stunned to see that the physical environment alone was telling the stem cells to become neurons or muscle or bone. "
Mesenchymal stem cells sense their environment through the force it takes them to push against surrounding objects. Each cell has its own skeleton and molecular motors that it uses as muscles. According to the researchers, the amount of force the stem cell needs to move its cellular muscles triggers an internal chemical signal that, in turn, directs the cell to differentiate.
"The cytoskeleton uses motors that, like our muscles, are based on the mechanical tension created by molecules of actin and myosin," Engler said. "When we deprive these stem cells of myosin, the cells do not respond to their physical environment, only their chemical environment."
But, the physical microenvironment can change due to injury and also in disease, which would make it difficult to use these stem cells in certain types of therapy. After a heart attack, for example, the heart becomes so scarred that stem cells seem ineffective in fixing the damage by turning into replacement cardiac muscle.
"The cardiac tissue may have been so damaged during the heart attack that the stem cells do not recognize the microenvironment as a guide for turning into heart muscle," Discher said; "however, our studies show that it might be possible to 'prime' stem cells for therapy in the lab, before implanting them in the heart, spine or whatever damaged environment you want to place them."
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Penn researchers involved in this study also include Shamik Sen from the School of Engineering and Applied Science. Funding for this research was provided by the National Institutes of Health, the Muscular Dystrophy Association and the National Science Foundation.
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"Ethics" is simply a last-gasp attempt by deist conservatives and
orthodox dogmatics to keep humanity in ignorance and obscurantism,
through the well tried fermentation of fear, the fear of science and
new technologies.
There is nothing glorious about what our ancestors call history,
it is simply a succession of mistakes, intolerances and violations.
On the contrary, let us embrace Science and the new technologies
unfettered, for it is these which will liberate mankind from the
myth of god, and free us from our age old fears, from disease,
death and the sweat of labour.
Rael
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