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MIT engineers report new approach to tissue engineering

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    MIT engineers report new approach to tissue engineering

    Public release date: 13-Oct-2003
    Contact: Elizabeth A. Thomson
    Massachusetts Institute of Technology
    MIT engineers report new approach to tissue engineering
    MIT engineers report a new approach to creating three-dimensional samples of human tissue that could push researchers closer to their ultimate goal: tissues for therapeutic applications and replacement organs. The technique could also help answer questions in cell and developmental biology.

    The team "seeded" human embryonic stem cells, which have the potential to differentiate into a variety of specialized cells, onto a biodegradable polymer scaffold. By treating the scaffold/stem cell structure with chemical cues, or growth factors, known to stimulate the formation of specific cell types, the researchers coaxed the stem cells to form tissues with characteristics of developing human cartilage, liver, nerves and blood vessels.

    "Here we show for the first time that polymer scaffolds � promoted proliferation, differentiation and organization of human embryonic stem cells into 3D structures," the researchers wrote in a paper to appear the week of Oct. 13 in the online edition of the Proceedings of the National Academy of Sciences.

    Further, the resulting tissues continued to thrive when implanted in mice with suppressed immune systems (to eliminate rejection). They expressed human proteins, and integrated with the host's blood-vessel networks.

    "For me it was very exciting to see that these [stem] cells could move around and start to 'talk' with one another, generating the different cell types common to a given tissue and organizing into that tissue," said Shulamit Levenberg, first author of the paper and a research associate in the Department of Chemical Engineering.

    The technique could also have an impact on the study of cell and developmental biology. "When you give cells a three-dimensional structure [on which to grow], it's really a lot more like what's happening in the embryo," said Levenberg, a mother of four whose youngest child is seven months old.

    Levenberg's colleagues on the work are Robert Langer, the Germeshausen Professor of Chemical and Biomedical Engineering; MIT alumna Ngan Huang (S.B. 2002); Erin Lavik, a postdoctoral fellow in the MIT-Harvard Division of Health Sciences and Technology who is now a professor at Yale; Arlin Rogers of MIT's Division of Comparative Medicine; and Joseph Itskovitz-Eldor of the Technion in Israel.

    The work provides a new approach to prodding stem cells to grow into different tissues. Before, researchers created a variety of cell types from one batch of stem cells, then isolated the cell type of interest. The isolated cells were then grown on a given medium, such as a polymer scaffold. The same MIT team did just that last year with the endothelial cells that blood vessels are composed of.

    This time around, the MIT researchers seeded stem cells directly into the scaffold. "We found that with different growth factors, we could push them in different directions," said Levenberg.

    The polymer scaffold is key. "The scaffold provides physical cues for cell orientation and spreading, and pores provide space for remodeling of tissue structures," the researchers wrote.

    The scaffold was carefully engineered. "If the scaffold is too soft," for example, "it collapses under the cells' mechanical forces," said Levenberg. The team also used two different polymers to create the scaffold. "One degrades quickly, the other more slowly," she said. "That gives cells room to grow while still retaining a support structure for them."

    The work was supported by the National Institutes of Health. The human embryonic stem cells are from an NIH-approved line.


    Scaffold Grows Organs from Stem Cells
    Dwayne Hunter
    Betterhumans Staff

    Monday, October 13, 2003, 4:56:58 PM CT

    A biodegradable polymer scaffold has encouraged stem cells to grow and differentiate into complex, 3D tissues, bringing scientists closer to engineering live human organs for transplant and having a new tool for studying early organ development.

    Researchers have long known that human embryonic stem cells hold promise for transplantation therapy because of their unique ability to differentiate into various cell types with the aid of chemical cues.

    However, it has been difficult to control cell proliferation and cell differentiation into higher-order structures that could be directly used for tissue engineering applications.

    Porous polymer

    The challenge of creating higher order structures from stem cells was taken up by Robert Langer and colleagues from the Department of Chemical Engineering at the Massachusetts Institute of Technology in Cambridge, Massachusetts.

    Langer's team hypothesized that porous biodegradable polymer scaffolds could be used to support embryonic stem cells as they formed complex 3D tissue structures during differentiation.

    The team developed a scaffold that provides physical cues for cell orientation and spreading and that has pores to provide space for remodeling of tissue structures.

    Within two weeks of constructing the 3D scaffolds from biodegradable polymers and inducing embryonic stem cell differentiation with growth factors such as RA, activin-A and insulin-like growth factor-I, Langer and colleagues got cells to exhibit 3D organization resembling primitive neural, cartilage and liver tissue, depending on which growth factors were added.

    Integrated into mice

    When transplanted into immune-deficient mice, the constructs expressed human proteins and integrated with their host's blood vessel networks.

    In the mice, the scaffold-supported embryonic stem cell constructs remained viable for at least two weeks.

    The approach provides a unique culture system for addressing questions in cell and developmental biology, and provides a potential mechanism for creating viable human tissue structures for therapeutic applications.

    Growth of human tissues in vitro holds promise for addressing organ shortages and infectious disease risks, which present serious challenges in transplantation medicine.

    The researchers say that further studies are required to promote tissue differentiation in vitro and in vivo and to address regulation of cellular proliferation.

    The work is reported in the Proceedings of the National Academy of Science (read abstract).


      in complete science

      I meant silence...[img]/forum/images/smilies/smile.gif[/img]


        Originally posted by Bubo-Hungary:

        in complete science

        I meant silence...[img]/forum/images/smilies/smile.gif[/img]
        my original question lost somehow.

        My remark was as chemical engineer that tissue engineering will be I think the final solution. Or.. I saw on TV that a doctor in Canada partially cured a man with parkinson's disease by injecting a modified virus into his brain which activaed certain nerve cells to produce neurotrophins.
        Maybe with a modified virus it will be possible to inject it to the SC force it to regenerate.

        My personal question to you was that in complete silence when I turn my head I hear a noise in my neck, I hear it since years. Also when I move my head suddenly I hear a crunch like sound in my neck. I am only 34. Is it possible that I broke my neck during regular use (turning in my bed while I am sleeping)?
        I have no osteoporosis, nor I never broke any bones of mine. I do not experience any similar phenomenon in any of my other parts of my body. Is it possible I break my spinal cord when I just turn my head?
        Thank you