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An Engineered Human Joint
RESEARCH UPDATE
doi:10.1016/mthe.2004.1150
An Engineered Human Joint
R
esearchers have used adult stem cells to form the ball-like structure of a joint found in the human jaw. Tested so far only in animals, the tissue-engineered “articular condyle” might be eventually used to regenerate joints in the jaw, knee or hip that have been lost to injury or diseases such as arthritis. A report on the tissue-engineered articular condyle will
human cadaver. After several weeks, Mao and his colleagues found that the structures retained the molded shape of the human mandibular condyle, with bone-like tissue underneath and a layer of cartilage-like tissue on top— an arrangement similar to that of a natural articular condyle. Moreover, multiple tests confirmed that the newly grown tissues were indeed bone and cartilage. Mao stressed that much additional work is needed before tissueengineered condyles are ready for therapeutic use in patients suffering from osteoarthritis, rheumatoid arthritis, injuries or congenital anomalies. The Journal of Dental Research, (2003), 82: 951-6, doi not provided by publisher.
Articular condoyle engineered from stem cells. Copyright © International and American Associations for Dental Research.
be published in the December 2003 issue of the Journal of Dental Research. “This represents the first time a human-shaped articular condyle with both cartilage- and bone-like tissues was grown from a single population of adult stem cells,” said author Jeremy Mao. “Our ultimate goal is to create a condyle that is biologically viable—a living tissue construct that integrates with existing bone and functions like the natural joint.” To create the articular condyle, the workers induced adult rat mesenchymal stem cells to develop into cells capable of producing cartilage and bone. The cells were then stratified into two integrated layers, encapsulated in a biocompatible gel-like material, and shaped into an articular condyle using a mold made from the temporomandibular or jaw joint of a
MOLECULAR THERAPY Vol. 9, No. 1, January 2004 Copyright © The American Society of Gene Therapy
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Ebola Vaccine Enters Human Trial
he first human trial of a DNA vaccine designed to prevent Ebola infection opened in November 2003. Scientists from the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID) designed the vaccine. Three years ago, VRC Director Gary Nabel, together with a team of scientists from the VRC and the Centers for Disease Control and Prevention, described an experimental Ebola vaccine that fully protected monkeys from lethal infection by the virus. One component of that vaccine will now be assessed for safety in human volunteers. “ This trial is further evidence of the ability of the VRC to rapidly translate basic research into tangible products,” notes NIAID Director Anthony S.
Fauci. “Our accelerated effort to understand and combat Ebola infection is part of the NIAID commitment to its biodefense mission. An effective Ebola vaccine not only would provide a life-saving advance in countries where the disease occurs naturally, it also would provide a medical tool to discourage the use of Ebola virus as an agent of bioterrorism.” Nabel notes, “The current Ebola outbreak in the Congo provides a stark reminder of the need to rapidly develop vaccines against such perilous infections. A few years ago, we did not imagine that our vaccine would enter human trials so quickly, but the re-emergence of such viruses makes it all the more important to respond quickly.” The investigational vaccine is manufactured by Vical Inc. Vical has also secured a nonexclusive license from NIH to proprietary gene sequences used in the vaccine. The candidate vaccine is synthesized using modified, inactivated genes from the Ebola virus. Ultimately, the scientists envision this vaccine as the first in a twostage vaccination strategy called prime-boost: after “priming” with the DNA vaccine, the immune system response is “boosted” by a second inoculation with modified, non-disease-causing cold viruses engineered to express Ebola proteins.
Ebola Virus. Image courtesy CDC.
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RESEARCH UPDATE
Regulatory T Cells Keep GVHD in Check
B
doi:10.1016/mthe.2004.1150
ulatory T cells to control GVHD. The Journal of Clinical Investigation, online edition, doi: 10.1172/JCI200317702
nerve regeneration during the same time period. These results suggest that biosynthetic corneas may provide a viable alternative to donor tissue transplants.
one marrow transplantation is an important treatment option for Artificial Biosynthetic patients suffering from certain forms The Proceedings of the National Academy of Cornea of cancer and immune deficiency disSciences, online edition, doi: 10.1073/pnas.2536767100 eases. However, there is a risk that tissue scaffold made from natural transplanted cells may recognize the and synthetic polymers can be recipient’s tissues as foreign and attack U.S. Poorly Prepared for used to grow corneal and nerve cells them. This reaction, known as graftInfluenza Pandemic for implantation, according to a new versus-host disease (GVHD), can be study appearing in the early online lethal if it continues unchecked. he United States is not adequately edition of the Proceedings of the In mice, the co-delivery of large prepared to respond to a worldNational Academy of Sciences. numbers of immunoregulatory CD4+, CD25+ T cells can induce tolerance to wide outbreak of influenza, according Corneal diseases affect over 10 mildonor tissue following allogeneic to an article in the 28 November 2003 lion people worldwide. Currently, the hematopoietic stem cell transplantaissue of the journal Science. The cusmain treatment for corneal blindness tion and therefore might be useful to tomary way to make a vaccine against is transplantation with human donor control the development of GVHD. a specific influenza virus is to let viral tissue. However, the demand outstrips The challenge however has been to genes mix inside chicken eggs. supply, and potential problems can obtain enough freshly purified CD4+, However, according to the authors, in result from the lack of nerve regeneraCD25+ regulatory T cells from a single the event of a pandemic, the process tion after surgery. donor to achieve this therapeutic of initially developing a “seed” virus In search of an alternative treateffect in a clinical setting. suitable for mass production as a vacment, May Griffith and colleagues In the December 4, 2004 issue of cine would be too slow. turned to tissue engineering. The the Journal of Clinical Investigation, José However, the use of reverse genetresearchers designed a matrix comCohen and colleagues describe a proics was shown earlier this year to draposed of the protein collagen and a tocol to circumvent this difficulty. The matically reduce the time to create the synthetic N-isopropylacrylamide-based authors performed regulatory T-cell seed virus. But reverse genetics polymer. This matrix had the same expansion ex vivo by stimulation with requires specific populations of animal optical clarity, curvature, and biomeallogeneic antigen-presenting cells, cells in which to grow the viruses, and chanical properties as a human which has the additional effect of prothere are only a few lines of cells suitcornea. In vitro studies demonstrated ducing alloantigen-specific regulatory able for this process. Most of those that the matrix could support corneal T cells. Regulatory T cells specific for cell lines are owned by large pharmaand nerve cell growth. When the recipient-type alloantigens, but not ceutical companies rather than acaresearchers transplanted the matrix irrelevant regulatory T cells, controlled demic research laboratories. into pigs with damaged corneas, nerve GVHD and favored immune reconstiLaboratories that produce seed vacregeneration occurred within 3 weeks. tution. Preferential survival of specific cines for influenza might need access In contrast, pigs receiving traditional regulatory T cells was observed in the to cell lines that are privately held. As donor transplantations exhibited no grafted anisuch, the authors suggest that mals. The in the event of a pandemic, results may international collaboration find applicawould be required between tion in the government, industry and design of academia, as occurred succlinical trials cessfully in the worldwide that rely on response to SARS earlier this the use of year. Corneal tissue is removed from a pig’s eye (A) and replaced with a biosynthetic implant (B, CD4+, Science, online edition, doi: arrow), which is sutured in place (C, arrows indicate sutures). Copyright © The National Academy CD25+ reg10.1126/science.1090350 of Science.
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MOLECULAR THERAPY Vol. 9, No. 1, January 2004 Copyright © The American Society of Gene Therapy
doi:10.1016/mthe.2004.1150
An Engineered Human Joint
R
esearchers have used adult stem cells to form the ball-like structure of a joint found in the human jaw. Tested so far only in animals, the tissue-engineered “articular condyle” might be eventually used to regenerate joints in the jaw, knee or hip that have been lost to injury or diseases such as arthritis. A report on the tissue-engineered articular condyle will
human cadaver. After several weeks, Mao and his colleagues found that the structures retained the molded shape of the human mandibular condyle, with bone-like tissue underneath and a layer of cartilage-like tissue on top— an arrangement similar to that of a natural articular condyle. Moreover, multiple tests confirmed that the newly grown tissues were indeed bone and cartilage. Mao stressed that much additional work is needed before tissueengineered condyles are ready for therapeutic use in patients suffering from osteoarthritis, rheumatoid arthritis, injuries or congenital anomalies. The Journal of Dental Research, (2003), 82: 951-6, doi not provided by publisher.
Articular condoyle engineered from stem cells. Copyright © International and American Associations for Dental Research.
be published in the December 2003 issue of the Journal of Dental Research. “This represents the first time a human-shaped articular condyle with both cartilage- and bone-like tissues was grown from a single population of adult stem cells,” said author Jeremy Mao. “Our ultimate goal is to create a condyle that is biologically viable—a living tissue construct that integrates with existing bone and functions like the natural joint.” To create the articular condyle, the workers induced adult rat mesenchymal stem cells to develop into cells capable of producing cartilage and bone. The cells were then stratified into two integrated layers, encapsulated in a biocompatible gel-like material, and shaped into an articular condyle using a mold made from the temporomandibular or jaw joint of a
MOLECULAR THERAPY Vol. 9, No. 1, January 2004 Copyright © The American Society of Gene Therapy
T
Ebola Vaccine Enters Human Trial
he first human trial of a DNA vaccine designed to prevent Ebola infection opened in November 2003. Scientists from the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID) designed the vaccine. Three years ago, VRC Director Gary Nabel, together with a team of scientists from the VRC and the Centers for Disease Control and Prevention, described an experimental Ebola vaccine that fully protected monkeys from lethal infection by the virus. One component of that vaccine will now be assessed for safety in human volunteers. “ This trial is further evidence of the ability of the VRC to rapidly translate basic research into tangible products,” notes NIAID Director Anthony S.
Fauci. “Our accelerated effort to understand and combat Ebola infection is part of the NIAID commitment to its biodefense mission. An effective Ebola vaccine not only would provide a life-saving advance in countries where the disease occurs naturally, it also would provide a medical tool to discourage the use of Ebola virus as an agent of bioterrorism.” Nabel notes, “The current Ebola outbreak in the Congo provides a stark reminder of the need to rapidly develop vaccines against such perilous infections. A few years ago, we did not imagine that our vaccine would enter human trials so quickly, but the re-emergence of such viruses makes it all the more important to respond quickly.” The investigational vaccine is manufactured by Vical Inc. Vical has also secured a nonexclusive license from NIH to proprietary gene sequences used in the vaccine. The candidate vaccine is synthesized using modified, inactivated genes from the Ebola virus. Ultimately, the scientists envision this vaccine as the first in a twostage vaccination strategy called prime-boost: after “priming” with the DNA vaccine, the immune system response is “boosted” by a second inoculation with modified, non-disease-causing cold viruses engineered to express Ebola proteins.
Ebola Virus. Image courtesy CDC.
3
RESEARCH UPDATE
Regulatory T Cells Keep GVHD in Check
B
doi:10.1016/mthe.2004.1150
ulatory T cells to control GVHD. The Journal of Clinical Investigation, online edition, doi: 10.1172/JCI200317702
nerve regeneration during the same time period. These results suggest that biosynthetic corneas may provide a viable alternative to donor tissue transplants.
one marrow transplantation is an important treatment option for Artificial Biosynthetic patients suffering from certain forms The Proceedings of the National Academy of Cornea of cancer and immune deficiency disSciences, online edition, doi: 10.1073/pnas.2536767100 eases. However, there is a risk that tissue scaffold made from natural transplanted cells may recognize the and synthetic polymers can be recipient’s tissues as foreign and attack U.S. Poorly Prepared for used to grow corneal and nerve cells them. This reaction, known as graftInfluenza Pandemic for implantation, according to a new versus-host disease (GVHD), can be study appearing in the early online lethal if it continues unchecked. he United States is not adequately edition of the Proceedings of the In mice, the co-delivery of large prepared to respond to a worldNational Academy of Sciences. numbers of immunoregulatory CD4+, CD25+ T cells can induce tolerance to wide outbreak of influenza, according Corneal diseases affect over 10 mildonor tissue following allogeneic to an article in the 28 November 2003 lion people worldwide. Currently, the hematopoietic stem cell transplantaissue of the journal Science. The cusmain treatment for corneal blindness tion and therefore might be useful to tomary way to make a vaccine against is transplantation with human donor control the development of GVHD. a specific influenza virus is to let viral tissue. However, the demand outstrips The challenge however has been to genes mix inside chicken eggs. supply, and potential problems can obtain enough freshly purified CD4+, However, according to the authors, in result from the lack of nerve regeneraCD25+ regulatory T cells from a single the event of a pandemic, the process tion after surgery. donor to achieve this therapeutic of initially developing a “seed” virus In search of an alternative treateffect in a clinical setting. suitable for mass production as a vacment, May Griffith and colleagues In the December 4, 2004 issue of cine would be too slow. turned to tissue engineering. The the Journal of Clinical Investigation, José However, the use of reverse genetresearchers designed a matrix comCohen and colleagues describe a proics was shown earlier this year to draposed of the protein collagen and a tocol to circumvent this difficulty. The matically reduce the time to create the synthetic N-isopropylacrylamide-based authors performed regulatory T-cell seed virus. But reverse genetics polymer. This matrix had the same expansion ex vivo by stimulation with requires specific populations of animal optical clarity, curvature, and biomeallogeneic antigen-presenting cells, cells in which to grow the viruses, and chanical properties as a human which has the additional effect of prothere are only a few lines of cells suitcornea. In vitro studies demonstrated ducing alloantigen-specific regulatory able for this process. Most of those that the matrix could support corneal T cells. Regulatory T cells specific for cell lines are owned by large pharmaand nerve cell growth. When the recipient-type alloantigens, but not ceutical companies rather than acaresearchers transplanted the matrix irrelevant regulatory T cells, controlled demic research laboratories. into pigs with damaged corneas, nerve GVHD and favored immune reconstiLaboratories that produce seed vacregeneration occurred within 3 weeks. tution. Preferential survival of specific cines for influenza might need access In contrast, pigs receiving traditional regulatory T cells was observed in the to cell lines that are privately held. As donor transplantations exhibited no grafted anisuch, the authors suggest that mals. The in the event of a pandemic, results may international collaboration find applicawould be required between tion in the government, industry and design of academia, as occurred succlinical trials cessfully in the worldwide that rely on response to SARS earlier this the use of year. Corneal tissue is removed from a pig’s eye (A) and replaced with a biosynthetic implant (B, CD4+, Science, online edition, doi: arrow), which is sutured in place (C, arrows indicate sutures). Copyright © The National Academy CD25+ reg10.1126/science.1090350 of Science.
A
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MOLECULAR THERAPY Vol. 9, No. 1, January 2004 Copyright © The American Society of Gene Therapy