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News Article | May 17, 2017
Site: www.sciencedaily.com

Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance, published in the journal Nature, opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived from patients' own cells. "We're tantalizingly close to generating bona fide human blood stem cells in a dish," says senior investigator George Daley, MD, PhD, who heads a research lab in Boston Children's Hospital's Stem Cell Program and is dean of Harvard Medical School. "This work is the culmination of over 20 years of striving." Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice. "This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," says Ryohichi (Rio) Sugimura, MD, PhD, the study's first author and a postdoctoral fellow in the Daley Lab. "This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions." Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells. In 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming. iPS cells were later used to generate multiple human cell types, such as neurons and heart cells -- yet blood-forming stem cells remained elusive. Sugimura, Daley and colleagues combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialized cells and tissues during normal embryonic development. This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish. In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood-forming state. Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells. They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy. Finally, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation. These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination. ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease. "We're now able to model human blood function in so-called 'humanized mice,'" says Daley. "This is a major step forward for our ability to investigate genetic blood disease." The researchers' technique produced a mixture of blood stem cells and so-called hematopoietic progenitor cells, which also give rise to blood cells. Their ultimate goal is to expand their ability to make true blood stem cells in a way that's practical and safe, without the need for viruses to deliver the transcription factors, and to introduce gene-editing techniques like CRISPR to correct genetic defects in pluripotent stem cells before blood cells are made. One challenge in making bona-fide human blood stem cells is that no one's been able to fully characterize these cells. "It's proved challenging to 'see' these cells," says Sugimura. "You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can't go back and study it -- it's already gone. A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona-fide human blood stem cells."


News Article | May 18, 2017
Site: www.biosciencetechnology.com

Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance, published today in the journal Nature, opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived from patients' own cells. "We're tantalizingly close to generating bona fide human blood stem cells in a dish," says senior investigator George Daley, MD, PhD, who heads a research lab in Boston Children's Hospital's Stem Cell Program and is dean of Harvard Medical School. "This work is the culmination of over 20 years of striving." Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice. "This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," says Ryohichi (Rio) Sugimura, MD, PhD, the study's first author and a postdoctoral fellow in the Daley Lab. "This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions." Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells. In 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming. iPS cells were later used to generate multiple human cell types, such as neurons and heart cells -- yet blood-forming stem cells remained elusive. Sugimura, Daley and colleagues combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialized cells and tissues during normal embryonic development. This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish. In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood-forming state. Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells. They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy. Finally, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation. These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination. ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease. "We're now able to model human blood function in so-called 'humanized mice,'" says Daley. "This is a major step forward for our ability to investigate genetic blood disease." The researchers' technique produced a mixture of blood stem cells and so-called hematopoietic progenitor cells, which also give rise to blood cells. Their ultimate goal is to expand their ability to make true blood stem cells in a way that's practical and safe, without the need for viruses to deliver the transcription factors, and to introduce gene-editing techniques like CRISPR to correct genetic defects in pluripotent stem cells before blood cells are made. One challenge in making bona-fide human blood stem cells is that no one's been able to fully characterize these cells. "It's proved challenging to 'see' these cells," says Sugimura. "You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can't go back and study it -- it's already gone. A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona-fide human blood stem cells."


News Article | May 19, 2017
Site: www.biosciencetechnology.com

Researchers from Cedars Sinai Medical Center have developed a new technique that, if successful in humans, could replace traditional bone grafts for mending nonhealing limb fractures. The new method, which combines, microbubbles, ultrasound, and gene and stem cell therapies, effectively healed severely broken bones in a study in pigs. In the U.S., approximately 100,000 bones fail to heal correctly, and more than 2 million bone grafts are performed around the globe each year. Bone grafts bridge gaps between the edges of a fracture that are too big for the bone to heal on its own.  There are two kinds of bone grafts: autologous, where bone is taken from the patient’s own body, or allogeneic, where it is taken from a tissue bank. However, both have drawbacks. Autografts, which are considered the current gold standard, are not always available in the volume required, may cause prolonged pain because of the second surgical site, and entail risk of infection and more time spent in the hospital, Gadi Pelled, Ph.D., DMD, assistant professor of surgery at Cedars-Sinai and the study’s co-senior author explained in an interview with Bioscience Technology. “Allografts are readily available from tissue banks, but have a low capacity to form new bone and integrate with the patient’s bones,” he said. “They also have the risk of immune rejection and disease transmission.” Hence, there is a large unmet need in skeleton repair. For the new study, researchers built a scaffold made of collagen, which is a protein the body uses to build bones.  It was implanted at the site of the bone break in laboratory pigs for two weeks, during which it “attracted" stem cells from adjacent bone marrow to populate the injury site, principal investigator and co-senior author of the study Dan Gazit, Ph.D. DMD, co-director of the Skeletal Regeneration and Stem Cell Therapy program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute told Bioscience Technology. Next they injected microbubbles combined with genetic material called a plasmid, which is a short circular strand of DNA that codes for a protein known to induce new bone formation. The DNA can’t enter the cells on its own, so ultrasound pulses and microbubbles facilitate the DNA entry across the cell membrane in a process called sonoporation, Gazit said. “The ultrasound waves cause the microbubbles to oscillate, i.e. inflate and deflate,” Gazit explained. “The oscillation pulls gently on the cell membrane leading to the opening of tiny pores, which shut down very quickly, through which the DNA enters the cells.” The technique promoted total bone healing and the leg fracture was mended in all of the animals within eight weeks after surgery.  Expression of the introduced gene was undetectable after 10 days, and the bone grown in fracture had comparable strength to those produced by surgical bone grafts. “This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat nonhealing bone fractures,” Pelled said in a statement. “It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.” Zulma Gazit, Ph.D., co-director of the Skeletal Regeneration and Stem Cell Program in the Depart of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute and co-author of the study, told Bioscience Technology that the team hopes the technique will translate into humans, and they are actively working towards that goal. “If our technique is successful, bone grafts would not be needed for these types of bone loss cases,” she said. “In addition, we see great promise in the technology for the regeneration and repair of other tissues such as muscle ligaments and more. Wherever stem cells can be recruited and the regeneration factor (gene) is known, the system may be beneficial.” Up next the team is planning to perform comprehensive research to address any concern about the safety of the technology prior to human trials. “We are just at the beginning of a revolution in orthopedics,” Dan Gazit said in a statement. “We’re combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine.” The findings were detailed in a paper published May 17 in Science Translational Medicine.


News Article | May 19, 2017
Site: www.chromatographytechniques.com

Researchers from Cedars Sinai Medical Center have developed a new technique that, if successful in humans, could replace traditional bone grafts for mending nonhealing limb fractures. The new method, which combines, microbubbles, ultrasound, and gene and stem cell therapies, effectively healed severely broken bones in a study in pigs. In the U.S., approximately 100,000 bones fail to heal correctly, and more than 2 million bone grafts are performed around the globe each year. Bone grafts bridge gaps between the edges of a fracture that are too big for the bone to heal on its own.  There are two kinds of bone grafts: autologous, where bone is taken from the patient’s own body, or allogeneic, where it is taken from a tissue bank. However, both have drawbacks. Autografts, which are considered the current gold standard, are not always available in the volume required, may cause prolonged pain because of the second surgical site, and entail risk of infection and more time spent in the hospital, Gadi Pelled, Ph.D., DMD, assistant professor of surgery at Cedars-Sinai and the study’s co-senior author explained in an interview with Bioscience Technology. “Allografts are readily available from tissue banks, but have a low capacity to form new bone and integrate with the patient’s bones,” he said. “They also have the risk of immune rejection and disease transmission.” Hence, there is a large unmet need in skeleton repair. For the new study, researchers built a scaffold made of collagen, which is a protein the body uses to build bones.  It was implanted at the site of the bone break in laboratory pigs for two weeks, during which it “attracted" stem cells from adjacent bone marrow to populate the injury site, principal investigator and co-senior author of the study Dan Gazit, Ph.D. DMD, co-director of the Skeletal Regeneration and Stem Cell Therapy program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute told Bioscience Technology. Next they injected microbubbles combined with genetic material called a plasmid, which is a short circular strand of DNA that codes for a protein known to induce new bone formation. The DNA can’t enter the cells on its own, so ultrasound pulses and microbubbles facilitate the DNA entry across the cell membrane in a process called sonoporation, Gazit said. “The ultrasound waves cause the microbubbles to oscillate, i.e. inflate and deflate,” Gazit explained. “The oscillation pulls gently on the cell membrane leading to the opening of tiny pores, which shut down very quickly, through which the DNA enters the cells.” The technique promoted total bone healing and the leg fracture was mended in all of the animals within eight weeks after surgery.  Expression of the introduced gene was undetectable after 10 days, and the bone grown in fracture had comparable strength to those produced by surgical bone grafts. “This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat nonhealing bone fractures,” Pelled said in a statement. “It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.” Zulma Gazit, Ph.D., co-director of the Skeletal Regeneration and Stem Cell Program in the Depart of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute and co-author of the study, told Bioscience Technology that the team hopes the technique will translate into humans, and they are actively working towards that goal. “If our technique is successful, bone grafts would not be needed for these types of bone loss cases,” she said. “In addition, we see great promise in the technology for the regeneration and repair of other tissues such as muscle ligaments and more. Wherever stem cells can be recruited and the regeneration factor (gene) is known, the system may be beneficial.” Up next the team is planning to perform comprehensive research to address any concern about the safety of the technology prior to human trials. “We are just at the beginning of a revolution in orthopedics,” Dan Gazit said in a statement. “We’re combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine.” The findings were detailed in a paper published May 17 in Science Translational Medicine.


News Article | May 17, 2017
Site: www.eurekalert.org

Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance, published today in the journal Nature, opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived from patients' own cells. "We're tantalizingly close to generating bona fide human blood stem cells in a dish," says senior investigator George Daley, MD, PhD, who heads a research lab in Boston Children's Hospital's Stem Cell Program and is dean of Harvard Medical School. "This work is the culmination of over 20 years of striving." Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice. "This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," says Ryohichi (Rio) Sugimura, MD, PhD, the study's first author and a postdoctoral fellow in the Daley Lab. "This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions." Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells. In 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming. iPS cells were later used to generate multiple human cell types, such as neurons and heart cells -- yet blood-forming stem cells remained elusive. Sugimura, Daley and colleagues combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialized cells and tissues during normal embryonic development. This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish. In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood-forming state. Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells. They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy. Finally, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation. These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination. ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease. "We're now able to model human blood function in so-called 'humanized mice,'" says Daley. "This is a major step forward for our ability to investigate genetic blood disease." The researchers' technique produced a mixture of blood stem cells and so-called hematopoietic progenitor cells, which also give rise to blood cells. Their ultimate goal is to expand their ability to make true blood stem cells in a way that's practical and safe, without the need for viruses to deliver the transcription factors, and to introduce gene-editing techniques like CRISPR to correct genetic defects in pluripotent stem cells before blood cells are made. One challenge in making bona-fide human blood stem cells is that no one's been able to fully characterize these cells. "It's proved challenging to 'see' these cells," says Sugimura. "You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can't go back and study it -- it's already gone. A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona-fide human blood stem cells." The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R24DK092760), the National Institute of Allergy and Infectious Diseases (R37AI039394), the National Heart, Lung, Blood Institute Progenitor Cell Biology Consortium (UO1-HL100001), Alex's Lemonade Stand, the Doris Duke Medical Foundation, the American Society of Hematology Scholar Fellowship and the Howard Hughes Medical Institute. Boston Children's Hospital is home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including seven members of the National Academy of Sciences, 11 members of the Institute of Medicine and 10 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 415-bed comprehensive center for pediatric and adolescent health care. Boston Children's is also the primary pediatric teaching affiliate of Harvard Medical School. For more, visit our Vector and Thriving blogs and follow us on our social media channels: @BostonChildrens, @BCH_Innovation, Facebook and YouTube.


News Article | May 18, 2017
Site: www.biosciencetechnology.com

Researchers at Boston Children's Hospital have, for the first time, generated blood-forming stem cells in the lab using pluripotent stem cells, which can make virtually every cell type in the body. The advance, published today in the journal Nature, opens new avenues for research into the root causes of blood diseases and to creating immune-matched blood cells for treatment purposes, derived from patients' own cells. "We're tantalizingly close to generating bona fide human blood stem cells in a dish," says senior investigator George Daley, MD, PhD, who heads a research lab in Boston Children's Hospital's Stem Cell Program and is dean of Harvard Medical School. "This work is the culmination of over 20 years of striving." Although the cells made from the pluripotent stem cells are a mix of true blood stem cells and other cells known as blood progenitor cells, they proved capable of generating multiple types of human blood cells when put into mice. "This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," says Ryohichi (Rio) Sugimura, MD, PhD, the study's first author and a postdoctoral fellow in the Daley Lab. "This also gives us the potential to have a limitless supply of blood stem cells and blood by taking cells from universal donors. This could potentially augment the blood supply for patients who need transfusions." Since human embryonic stem (ES) cells were isolated in 1998, scientists have been trying, with little success, to use them to make blood-forming stem cells. In 2007, three groups (including the Daley lab) generated the first induced pluripotent stem (iPS) cells from human skin cells through genetic reprogramming. iPS cells were later used to generate multiple human cell types, such as neurons and heart cells -- yet blood-forming stem cells remained elusive. Sugimura, Daley and colleagues combined two previous approaches. First, they exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals that direct stem cells to differentiate into specialized cells and tissues during normal embryonic development. This generated hemogenic endothelium, an early embryonic tissue that eventually gives rise to blood stem cells, although the transition to blood stem cells had never been achieved in a dish. In the second step, the team added genetic regulatory factors (called transcription factors) to push the hemogenic endothelium toward a blood-forming state. Starting with 26 transcription factors identified as likely candidates, they eventually came down to just five (RUNX1, ERG, LCOR, HOXA5 and HOXA9) that were both necessary and sufficient for creating blood stem cells. They delivered the factors into the cells with a lentivirus, as used in some forms of gene therapy. Finally, they transplanted the genetically engineered hemogenic endothelial cells into mice. Weeks later, a small number of the animals carried multiple types of human blood cells in their bone marrow and blood circulation. These included red blood cell precursors, myeloid cells (precursors of monocytes, macrophages, neutrophils, platelets and other cells), and T and B lymphocytes. Some mice were able to mount a human immune response after vaccination. ES cells and iPS cells were similarly good at creating blood stem and progenitor cells when the technique was applied. But the researchers are most interested in iPS cells, which offer the added ability to derive cells directly from patients and model disease. "We're now able to model human blood function in so-called 'humanized mice,'" says Daley. "This is a major step forward for our ability to investigate genetic blood disease." The researchers' technique produced a mixture of blood stem cells and so-called hematopoietic progenitor cells, which also give rise to blood cells. Their ultimate goal is to expand their ability to make true blood stem cells in a way that's practical and safe, without the need for viruses to deliver the transcription factors, and to introduce gene-editing techniques like CRISPR to correct genetic defects in pluripotent stem cells before blood cells are made. One challenge in making bona-fide human blood stem cells is that no one's been able to fully characterize these cells. "It's proved challenging to 'see' these cells," says Sugimura. "You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you can't go back and study it -- it's already gone. A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona-fide human blood stem cells."


News Article | May 19, 2017
Site: www.chromatographytechniques.com

Researchers from Cedars Sinai Medical Center have developed a new technique that, if successful in humans, could replace traditional bone grafts for mending nonhealing limb fractures. The new method, which combines, microbubbles, ultrasound, and gene and stem cell therapies, effectively healed severely broken bones in a study in pigs. In the U.S., approximately 100,000 bones fail to heal correctly, and more than 2 million bone grafts are performed around the globe each year. Bone grafts bridge gaps between the edges of a fracture that are too big for the bone to heal on its own.  There are two kinds of bone grafts: autologous, where bone is taken from the patient’s own body, or allogeneic, where it is taken from a tissue bank. However, both have drawbacks. Autografts, which are considered the current gold standard, are not always available in the volume required, may cause prolonged pain because of the second surgical site, and entail risk of infection and more time spent in the hospital, Gadi Pelled, Ph.D., DMD, assistant professor of surgery at Cedars-Sinai and the study’s co-senior author explained in an interview with Bioscience Technology. “Allografts are readily available from tissue banks, but have a low capacity to form new bone and integrate with the patient’s bones,” he said. “They also have the risk of immune rejection and disease transmission.” Hence, there is a large unmet need in skeleton repair. For the new study, researchers built a scaffold made of collagen, which is a protein the body uses to build bones.  It was implanted at the site of the bone break in laboratory pigs for two weeks, during which it “attracted" stem cells from adjacent bone marrow to populate the injury site, principal investigator and co-senior author of the study Dan Gazit, Ph.D. DMD, co-director of the Skeletal Regeneration and Stem Cell Therapy program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute told Bioscience Technology. Next they injected microbubbles combined with genetic material called a plasmid, which is a short circular strand of DNA that codes for a protein known to induce new bone formation. The DNA can’t enter the cells on its own, so ultrasound pulses and microbubbles facilitate the DNA entry across the cell membrane in a process called sonoporation, Gazit said. “The ultrasound waves cause the microbubbles to oscillate, i.e. inflate and deflate,” Gazit explained. “The oscillation pulls gently on the cell membrane leading to the opening of tiny pores, which shut down very quickly, through which the DNA enters the cells.” The technique promoted total bone healing and the leg fracture was mended in all of the animals within eight weeks after surgery.  Expression of the introduced gene was undetectable after 10 days, and the bone grown in fracture had comparable strength to those produced by surgical bone grafts. “This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat nonhealing bone fractures,” Pelled said in a statement. “It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.” Zulma Gazit, Ph.D., co-director of the Skeletal Regeneration and Stem Cell Program in the Depart of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute and co-author of the study, told Bioscience Technology that the team hopes the technique will translate into humans, and they are actively working towards that goal. “If our technique is successful, bone grafts would not be needed for these types of bone loss cases,” she said. “In addition, we see great promise in the technology for the regeneration and repair of other tissues such as muscle ligaments and more. Wherever stem cells can be recruited and the regeneration factor (gene) is known, the system may be beneficial.” Up next the team is planning to perform comprehensive research to address any concern about the safety of the technology prior to human trials. “We are just at the beginning of a revolution in orthopedics,” Dan Gazit said in a statement. “We’re combining an engineering approach with a biological approach to advance regenerative engineering, which we believe is the future of medicine.” The findings were detailed in a paper published May 17 in Science Translational Medicine.


News Article | November 23, 2016
Site: www.eurekalert.org

Harvard Stem Cell Institute (HSCI) researchers have used a colorful, cell-labeling technique to track the development of the blood system and trace the lineage of adult blood cells travelling through the vast networks of veins, arteries, and capillaries back to their parent stem cell in the marrow. Their findings have already advanced the understanding of blood development as well as blood diseases. Developed at Harvard's Center for Brain Science, the technique involves coding multiple colors of florescent protein into a cell's DNA. As genes recombine inside the cell, the cell elaborates a color unique to its genetic code. For blood stem cells, that color becomes a genetic signature passed down to daughter cells; purple stem cells, for example, will only make purple blood cells. Two independent research teams, one led by David Scadden, HSCI co-director and Gerald and Darlene Jordan Professor of Medicine at Harvard University, and the other by his colleague Leonard Zon, HSCI Executive Committee member and director of the Stem Cell Program at Boston Children's Hospital, adapted the color-based labeling to the blood system to better understand how blood stem cells behave. In a study recently published in Nature Cell Biology, a research team led by Scadden found that in mice individual blood stem cells had a specific and restricted blood production repertoire. "We used to think of stem cells as the mother cell that gives rise to all these other cells in the system on an as needed basis," said Vionnie Yu, first author of the study and, at the time of the research, a postdoctoral fellow in Scadden's lab. But their results suggest that stem cells have a scripted set of responses and cannot make just any blood cell type. When transplanted into a new environment, each cell not only consistently made the same mature blood cell types but also the same number of those cells. Additionally, clones responded similarly to inflammatory and chemotoxic stress, suggesting the cells had a hardwired memory dictating their behavior. They found that this memory was written into the stem cell epigenome. Blood stem cells, said Scadden, may be more like chess pieces with a fixed way they can behave within the system. "When you are young and have a full chess set you can mount a vigorous and multilayered defense to an attack on your system," Scadden said, "but if you lose chess pieces with age or you don't receive a full suite of players during a bone marrow transplant, the pieces you have left could determine your ability to protect yourself." In addition to looking at blood stem cells in adult mice, color tagging also allows researchers to explore the blood system as a zebrafish embryo develops. "We've been working with David Scadden for years as part of the HSCI. Initially, we presented our work at a joint lab meeting and realized we could study stem cell clones with this multi-color system," said Zon, who is also a professor in Harvard's Stem Cell and Regenerative Biology department. "We shared ideas and results, and even wrote a grant together on the topic. It is wonderful that studying clonal dynamics in two different animals could provide such complementary information." In a study published yesterday in Nature Cell Biology, the researcher team led by Zon used the color tagging system to define the origin and number of stem cells that contribute to lifelong blood production. About 24 to 30 hours after fertilization, dozens of stem cells budded off from the dorsal side of the aorta. Only twenty made it to a secondary site before heading to the kidney marrow, the zebrafish equivalent to human and mouse bone marrow. After transplanting the multicolored marrow into fish that had received sublethal doses of radiation, the researchers found that some blood stem cell lineages supplied a greater proportion of blood than they had before and that certain lineages could survive harsher conditions than others. Knowing which cells are responsible for blood production could have implications for understanding the development of blood cancers, explains Jonathan Henninger, a graduate student in Zon's lab at Boston Children's Hospital and first author in the study. For example, one blood stem cell could develop a mutation that gives it a competitive edge, allowing it to take over the blood system. "If that cell starts behaving badly, it could lead to blood disorders, such as myeloid dysplasia and leukemia," Henninger said. Researchers know these disorders come from a single stem cell or a downstream progenitor cell, said Henninger, but right now they are looking at populations of stem cells in bulk. "To be able to identify that single cell that went awry could help us better understand these diseases."


PubMed | Stem Cell Program, University of California at San Diego, California State University, Chico and Academy of Sciences of the Czech Republic
Type: Journal Article | Journal: Nature protocols | Year: 2016

This protocol describes the ex vivo characterization of zebrafish hematopoietic progenitors. We show how to isolate zebrafish hematopoietic cells for cultivation and differentiation in colony assays in semi-solid media. We also describe procedures for the generation of recombinant zebrafish cytokines and for the isolation of carp serum, which are essential components of the medium required to grow zebrafish hematopoietic cells ex vivo. The outcome of these clonal assays can easily be evaluated using standard microscopy techniques after 3-10 d in culture. In addition, we describe how to isolate individual colonies for further imaging and gene expression profiling. In other vertebrate model organisms, ex vivo assays have been crucial for elucidating the relationships among hematopoietic stem cells (HSCs), progenitor cells and their mature progeny. The present protocol should facilitate such studies on cells derived from zebrafish.


SAN FRANCISCO, Nov. 16, 2016 /PRNewswire/ -- Aelan Cell Technologies, Inc. (www.aelanct.com) announced today that Meenakshi Gaur, Ph.D., Director of Stem Cell Program at Aelan, will give a presentation titled "TIME DEPENDENT CHANGE IN THE SECRETION OF BIOLOGICS AND IMMUNOMODULATORY CAPACIT...

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