(Press-News.org) Contact information: Kat Kearney
kkearney@salk.edu
619-296-8455
Salk Institute
Salk scientists for the first time generate 'mini-kidney' structures from human stem cells
Findings may lead to much-needed therapies for kidney disease
LA JOLLA, CA— Diseases affecting the kidneys represent a major and unsolved health issue worldwide. The kidneys rarely recover function once they are damaged by disease, highlighting the urgent need for better knowledge of kidney development and physiology.
Now, a team of researchers led by scientists at the Salk Institute for Biological Studies has developed a novel platform to study kidney diseases, opening new avenues for the future application of regenerative medicine strategies to help restore kidney function.
For the first time, the Salk researchers have generated three-dimensional kidney structures from human stem cells, opening new avenues for studying the development and diseases of the kidneys and to the discovery of new drugs that target human kidney cells. The findings were reported November 17 in Nature Cell Biology.
Scientists had created precursors of kidney cells using stem cells as recently as this past summer, but the Salk team was the first to coax human stem cells into forming three-dimensional cellular structures similar to those found in our kidneys.
"Attempts to differentiate human stem cells into renal cells have had limited success," says senior study author Juan Carlos Izpisua Belmonte, a professor in Salk's Gene Expression Laboratory and holder of the Roger Guillemin Chair. "We have developed a simple and efficient method that allows for the differentiation of human stem cells into well-organized 3D structures of the ureteric bud (UB), which later develops into the collecting duct system."
The Salk findings demonstrate for the first time that pluripotent stem cells (PSCs)—cells capable of differentiating into the many cells and tissue types that make up the body—can made to develop into cells similar to those found in the ureteric bud, an early developmental structure of the kidneys, and then be further differentiated into three-dimensional structures in organ cultures. UB cells form the early stages of the human urinary and reproductive organs during development and later develop into a conduit for urine drainage from the kidneys. The scientists accomplished this with both human embryonic stem cells and induced pluripotent stem cells (iPSCs), human cells from the skin that have been reprogrammed into their pluripotent state.
After generating iPSCs that demonstrated pluripotent properties and were able to differentiate into mesoderm, a germ cell layer from which the kidneys develop, the researchers made use of growth factors known to be essential during the natural development of our kidneys for the culturing of both iPSCs and embryonic stem cells. The combination of signals from these growth factors, molecules that guide the differentiation of stem cells into specific tissues, was sufficient to commit the cells toward progenitors that exhibit clear characteristics of renal cells in only four days.
The researchers then guided these cells to further differentiated into organ structures similar to those found in the ureteric bud by culturing them with kidney cells from mice. This demonstrated that the mouse cells were able to provide the appropriate developmental cues to allow human stem cells to form three-dimensional structures of the kidney.
In addition, Izpisua Belmonte's team tested their protocol on iPSCs from a patient clinically diagnosed with polycystic kidney disease (PKD), a genetic disorder characterized by multiple, fluid-filled cysts that can lead to decreased kidney function and kidney failure. They found that their methodology could produce kidney structures from patient-derived iPSCs.
Because of the many clinical manifestations of the disease, neither gene- nor antibody-based therapies are realistic approaches for treating PKD. The Salk team's technique might help circumvent this obstacle and provide a reliable platform for pharmaceutical companies and other investigators studying drug-based therapeutics for PKD and other kidney diseases.
"Our differentiation strategies represent the cornerstone of disease modeling and drug discovery studies," says lead study author Ignacio Sancho-Martinez, a research associate in Izpisua Belmonte's laboratory. "Our observations will help guide future studies on the precise cellular implications that PKD might play in the context of kidney development."
INFORMATION:
Other researchers on the study were Yun Xia, Emmanuel Nivet, Thomas Gallegos, Keiichiro Suzuki, Daiji Okamura, Min-Zu Wu, Ilir Dubova, and Concepion Rodriguez Esteban, from the Salk Institute; Nuria Montserrat of the Center of Regenerative Medicine in Barcelona, Spain; and Josep Maria Campistol of the Hospital Clinic of Barcelona.
The work was supported by the California Institute for Regenerative Medicine, the Nomis Foundation, Fundacion Cellex, the G. Harold and Leila Y. Mathers Charitable Foundation, the Leona M. and Harry B. Helmsley Charitable Trust, Fundaciό La Maratό de TV3, CIBER BBN and ISCIII-TERCEL-MINECO.
About the Salk Institute for Biological Studies:
The Salk Institute for Biological Studies is one of the world's preeminent basic research institutions, where internationally renowned faculty probe fundamental life science questions in a unique, collaborative, and creative environment. Focused on both discovery and on mentoring future generations of researchers, Salk scientists make groundbreaking contributions to our understanding of cancer, aging, Alzheimer's, diabetes and infectious diseases by studying neuroscience, genetics, cell and plant biology, and related disciplines.
Faculty achievements have been recognized with numerous honors, including Nobel Prizes and memberships in the National Academy of Sciences. Founded in 1960 by polio vaccine pioneer Jonas Salk, M.D., the Institute is an independent nonprofit organization and architectural landmark.
Salk scientists for the first time generate 'mini-kidney' structures from human stem cells
Findings may lead to much-needed therapies for kidney disease
2013-11-18
ELSE PRESS RELEASES FROM THIS DATE:
Scientists fingerprint single cancer cells to map cancer's family tree
2013-11-18
Scientists fingerprint single cancer cells to map cancer's family tree
A new method to take the DNA fingerprint of individual cancer cells is uncovering the true extent of cancer's genetic diversity, new research reveals
A new method to take the DNA fingerprint ...
Evidence found for granite on Mars
2013-11-18
Evidence found for granite on Mars
Researchers now have stronger evidence of granite on Mars and a new theory for how the granite – an igneous rock common on Earth -- could have formed there, according to a new study. The findings suggest a much ...
Columbia engineers make world's smallest FM radio transmitter
2013-11-18
Columbia engineers make world's smallest FM radio transmitter
Team demonstrates new application of graphene using positive feedback
New York, NY—November 17, 2013—A team of Columbia Engineering researchers, led by Mechanical Engineering Professor James Hone and ...
Researchers capture structure of key part of deadly Nipah virus
2013-11-18
Researchers capture structure of key part of deadly Nipah virus
What began as a summer internship project designed for an undergraduate student evolved into a one-year study of one of the deadliest, but little known viruses. Researchers at The Scripps Research Institute ...
Novel study charts aggressive prostate cancer
2013-11-18
Novel study charts aggressive prostate cancer
Study in the Journal Cell Cycle reveals new developments in prognosis
LOS ANGELES (Nov. 18, 2013) – Many patients diagnosed with prostate cancer have indolent, slow-growing forms of the disease that are not life-threatening. ...
New research finds link between red cell distribution width levels and depression in heart patients
2013-11-18
New research finds link between red cell distribution width levels and depression in heart patients
DALLAS – Researchers at the Intermountain Medical Center Heart Institute have discovered a link between elevated red cell distribution width levels and ...
Long-term oral contraceptive users are twice as likely to have serious eye disease
2013-11-18
Long-term oral contraceptive users are twice as likely to have serious eye disease
Research shows birth control use over three years could be a risk factor for glaucoma
NEW ORLEANS – Nov. 18, 2013 – Research presented today, at the 117th Annual Meeting of the American ...
Faster surgery may be better for hip fractures: McMaster study
2013-11-18
Faster surgery may be better for hip fractures: McMaster study
In many countries waits for hip surgery can be 24 hours or longer
Hamilton, Nov. 18, 2013 – The speed of surgery after a hip fracture may have a significant impact on outcomes for older patients, ...
Program helps at-risk family members of patients with heart disease improve their own heart health
2013-11-18
Program helps at-risk family members of patients with heart disease improve their own heart health
Randomized clinical trial
Family members of patients with heart disease adopted healthier lifestyles and decreased their risk of a cardiovascular ...
Early surgery for hip fractures in older adults may improve outcomes
2013-11-18
Early surgery for hip fractures in older adults may improve outcomes
Randomized controlled trial
Early surgery for hip fractures in older people may substantially improve outcomes for patients, according to the results from a randomized controlled ...
LAST 30 PRESS RELEASES:
Are lifetimes of big appliances really shrinking?
Pink skies
Monkeys are world’s best yodellers - new research
Key differences between visual- and memory-led Alzheimer’s discovered
% weight loss targets in obesity management – is this the wrong objective?
An app can change how you see yourself at work
NYC speed cameras take six months to change driver behavior, effects vary by neighborhood, new study reveals
New research shows that propaganda is on the rise in China
Even the richest Americans face shorter lifespans than their European counterparts, study finds
Novel genes linked to rare childhood diarrhea
New computer model reveals how Bronze Age Scandinavians could have crossed the sea
Novel point-of-care technology delivers accurate HIV results in minutes
Researchers reveal key brain differences to explain why Ritalin helps improve focus in some more than others
Study finds nearly five-fold increase in hospitalizations for common cause of stroke
Study reveals how alcohol abuse damages cognition
Medicinal cannabis is linked to long-term benefits in health-related quality of life
Microplastics detected in cat placentas and fetuses during early pregnancy
Ancient amphibians as big as alligators died in mass mortality event in Triassic Wyoming
Scientists uncover the first clear evidence of air sacs in the fossilized bones of alvarezsaurian dinosaurs: the "hollow bones" which help modern day birds to fly
Alcohol makes male flies sexy
TB patients globally often incur "catastrophic costs" of up to $11,329 USD, despite many countries offering free treatment, with predominant drivers of cost being hospitalization and loss of income
Study links teen girls’ screen time to sleep disruptions and depression
Scientists unveil starfish-inspired wearable tech for heart monitoring
Footprints reveal prehistoric Scottish lagoons were stomping grounds for giant Jurassic dinosaurs
AI effectively predicts dementia risk in American Indian/Alaska Native elders
First guideline on newborn screening for cystic fibrosis calls for changes in practice to improve outcomes
Existing international law can help secure peace and security in outer space, study shows
Pinning down the process of West Nile virus transmission
UTA-backed research tackles health challenges across ages
In pancreatic cancer, a race against time
[Press-News.org] Salk scientists for the first time generate 'mini-kidney' structures from human stem cellsFindings may lead to much-needed therapies for kidney disease