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Stem Cells
American scientists grew human esophageal organoids entirely using pluripotent stem cells (PSCs) for the first time, potentially leading to new personalised diagnostic methods and regenerative tissue therapies to treat or cure gastrointestinal disorders.
Jim Wells, Chief Scientific Officer at Cincinnati Children’s Centre for Stem Cell and Organoid Medicine (CuSTOM) and study lead investigator, said.
The study published on Thursday in the journal Cell Stem Cell reported a new method that used human PSCs to produce general esophageal tissues on precisely timed, step-by-step manipulations of genetic and biochemical signals that pattern and form embryonic endoderm and foregut tissues.
“In addition to being a new model to study birth defects like esophageal atresia, the organoids can be used to study diseases like eosinophilic esophagitis and Barrett’s metaplasia, or to bioengineer genetically matched esophageal tissue for individual patients,” said Wells.
The esophagus is a muscular tube that actively passes food from the mouth to the stomach.
The fully formed human esophageal organoids grew to a length of about 300 to 800 micrometers in about two months.
Those tests showed the bioengineered and biopsies tissues were strikingly similar in composition, according to the study.
The scientists focused in part on the gene Sox2 and its associated protein. They used mice, frogs and human tissue cultures to identify other genes and molecular pathways regulated by Sox2 during esophagus formation.
They found that during critical stages of embryonic development, the Sox2 gene blocks the programming and action of genetic pathways that direct cells to become respiratory instead of esophageal.
In addition, Sox2 protein can inhibit the signaling of a molecule called Wnt and thus, promote the formation and survival of esophageal tissues, according to the study.
In another test to help confirm the importance of Sox2 expression on esophageal formation, researchers studied the complete loss of Sox2 during the development process in mice.
The absence of Sox2 resulted in esophageal agenesis, a condition in which the esophagus terminates in a pouch and does not connect to the stomach.
The research team is continuing its studies into the bioengineering process for esophageal organoids and identifying future projects to advance the technology’s eventual therapeutic potential, according to Wells.
Similarly, a study published on Thursday in the journal Cell showed that human skeletal stem cells that become bone, cartilage, or stroma cells have been isolated from fetal and adult bones.
This is the first time that skeletal stem cells, which had been observed in rodent models, have been identified in humans, according to researchers at Stanford University School of Medicine.
The researchers were able to derive the skeletal stem cells from human induced pluripotent stem cells, opening up new therapeutic possibilities.
“Identifying this human skeletal stem cell and elucidating its lineage map will enable the molecular diagnosis and treatment of skeletal diseases,’’ said Senior Study Author, Michael Longaker, Stanford University.
Bones in mice and humans can recover from small- to moderate-sized defects, but adult cartilage tissues possess little to no regenerative ability.
Also, both mice and humans display severe age-related degeneration of skeletal tissues over time.
In the new study, Longaker and his collaborators found that those self-renewing and multi-potent cells were present in both fetal and adult human bone marrow tissues and could be derived from induced pluripotent stem cells (iPSCs).
iPSCs are a type of pluripotent stem cell that can be generated directly from adult cells.
Pluripotent stem cells can propagate indefinitely, and give rise to every other cell type in the body.
By defining the relationships between human skeletal stem cells and downstream skeletal progenitors, the researchers also created a detailed lineage map of stem-cell-mediated formation of skeletal tissues in humans.(Xinhua/NAN)
