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Scientists steer the development of stem cells to regenerate and repair organs
2024-12-20 - 2024-12
Investigators from Cedars-Sinai and the University of California, San Francisco (UCSF) have identified a new way to deliver instructions that tell stem cells to grow into specific bodily structures, a critical step in eventually regenerating and repairing tissues and organs.
The scientists engineered cells that form structures called "synthetic organizers." These organizers provided instructions to the stem cells through biochemical signals called morphogens, which stimulated and enabled the stem cells to grow into specific complex tissues and organ-like assemblies.
The research was conducted with mouse embryonic stem cells, and the findings were published in Cell.
"We can use these synthetic organizers to push the stem cells toward making different parts of the early embryo or toward making a heart or other organs," said Ophir Klein, MD, Ph.D., co-corresponding author of the study, executive vice dean of Children's Health and executive director of Cedars-Sinai Guerin Children's.
In one instance, scientists were able to induce the stem cells to begin to form a mouse body that stretched from head to tail, similar to regular embryonic development in the womb. In another instance, the scientists were able to spur the stem cells to generate a large heart-like structure complete with a central chamber and a regular beat, along with a network of early blood vessels.
"This type of synthetic organizer cell platform provides a new way to interface with stem cells and to program what they develop into," said Wendell Lim, Ph.D., co-corresponding author and professor of Cellular and Molecular Pharmacology at UCSF.
"By controlling and reshaping how stem cells differentiate and develop, it might allow us to grow better organs for transplantation or organoids for disease modeling and eventually utilize it to drive tissue regeneration in living patients."
To steer organizer cells and control stem cell development, the scientists uploaded genetic codes into the cells and engineered two key features in the cells.
First, they instructed the cells to stick to the stem cells in the form of a node or a shell clustering around the clump of stem cells. Second, the investigators engineered the organizer cells to produce specific biochemical signals crucial to inducing early embryonic development.
To effectively and precisely control the organizer cells, researchers developed a chemical switch within the cells, allowing scientists to turn the delivery of instructions to stem cells on or off. Additionally, they installed a "suicide" switch to eliminate the organizer cells when needed.
"These synthetic organizers show that we can provide more refined developmental instructions to stem cells by engineering where and when specific morphogen signals are provided," Lim said. "The organizer cells carry both spatial information and biochemical information, thus giving us an incredible amount of control that we have not had before."
Stem cells head to the clinic: treatments for cancer, diabetes and Parkinson’s disease could soon be here
2024-12-20 - 2024-12
The study is one of more than 100 clinical trials exploring the potential of stem cells to replace or supplement tissues in debilitating or life-threatening diseases, including cancer, diabetes, epilepsy, heart failure and some eye diseases. It’s a different approach from the unapproved therapies peddled by many shady clinics, which use types of stem cell that do not turn into new tissue.
All the trials are small and focus mainly on safety. And there are still substantial challenges, including defining which cells will be most fit for which purposes and working out how to bypass the need for immunosuppressant drugs that stop the body from rejecting the cells but increase the risk of infections.
Still, the flurry of clinical studies marks a turning point for stem-cell therapies. Following decades of intense research that has at times triggered ethical and political controversy, the safety and potential of stem cells for tissue regeneration is now being widely tested. “The rate of progress has been remarkable,” says stem-cell specialist Martin Pera at the Jackson Laboratory in Bar Harbor, Maine. “It’s just 26 years since we first learnt to culture human stem cells in flasks.”
Researchers expect some stem-cell therapies to enter the clinic soon. Treatments for some conditions, they say, could become part of general medicine in five to ten years.
Finding a source
Cassy’s symptoms began with a small, persistent tremor in his fingers when he was just 44. The characteristic motor symptoms of Parkinson’s are driven by the degeneration of dopamine-producing neurons called A9 cells in the brain’s substantia nigra. Drugs that replace the missing dopamine are effective, but have side effects including uncontrolled movements and impulsive behaviors. And as the disease progresses, the drugs’ efficacy wanes and the side effects worsen.
The idea of replacing the degenerated dopaminergic cells has a long history. During development, pluripotent ES cells, which have the potential to become many cell types, turn into the specialized cells of the brain, heart, lungs and so on. Theoretically, transplanted stem cells could repair any damaged tissue.
Parkinson’s lent itself to testing that theory. The first transplant of such cells took place in Sweden in 1987 using neurons from the developing brains of fetuses from terminated pregnancies, the only source of immature, or progenitor, neural cells at the time. Since then, more than 400 people with Parkinson’s have received such a transplant — with mixed results. Many people saw no benefit at all, or had debilitating side effects. But others improved so much that they no longer needed to take dopaminergic drugs.
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