UCLA stem cell scientists first to track joint cartilage development in humans

December 12, 2013

Stem cell researchers from UCLA have published the first study to identify the origin cells and track the early development of human articular cartilage, providing what could be a new cell source and biological roadmap for therapies to repair cartilage defects and damage from osteoarthritis.

Such transformative therapies could reach clinical trials within three years, said the scientists from UCLA's Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

The study, led by Dr. Denis Evseenko, an assistant professor of orthopedic surgery and head of UCLA's Laboratory of Connective Tissue Regeneration, was published online Dec. 12 in the journal Stem Cell Reports and will appear in a forthcoming print edition.

Articular cartilage, a highly specialized tissue formed from cells called chondrocytes, protects the bones of joints from forces associated with load-bearing and impact and allows nearly frictionless motion between the articular surfaces -- the areas where bone connects with other bones in a joint.

Cartilage injury and a lack of cartilage regeneration often lead to osteoarthritis, which involves the degradation of joints, including cartilage and bone. Osteoarthritis currently affects more than 20 million people in the U.S., making joint-surface restoration a major priority in modern medicine.

While scientists have studied the ability of different cell types to generate articular cartilage, none of the current cell-based repair strategies -- including expanded articular chondrocytes or mesenchymal stromal cells from adult bone marrow, adipose tissue, sinovium or amniotic fluid -- have generated long-lasting articular cartilage tissue in the laboratory.

For the current study, Evseenko and his colleagues used complex molecular biology techniques to determine which cells grown from embryonic stem cells, which can become any cell type in the body, were the progenitors of cartilage cells, or chondrocytes. They then tested and confirmed the growth of these progenitor cells into cartilage cells and monitored their growth progress, observing and recording important genetic features, or landmarks, that indicated the growth stages of these cells as they developed into the cartilage cells.

By bridging developmental biology and tissue engineering, Evseenko's discoveries represent a critical "missing link," providing scientists with checkpoints to tell if the cartilage cells are developing correctly.

"We began with three questions about cartilage development," Evseenko said. "We wanted to know the key molecular mechanisms, the key cell populations and the developmental stages in humans. We carefully studied how the chondrocytes developed, watching not only their genes but other biological markers that will allow us to apply the system for the improvement of current stem cell-based therapeutic approaches."

The research was also the first to employ the highest animal-free standards in attempting to generate all the key landmarks that allow the development of cell types that could be used in treatments to regrow damaged human cartilage. Stem cells are often grown using animal-based components, which help the stem cells flourish and grow, but such components can lead to unwanted variations and contamination. Evseenko's research process did not rely on any animal components, thus allowing for the potential production of therapies, such as stem cell serums, that are safe for humans.

Evseenko noted that in a living organism, more than one cell type is responsible for the complete regeneration of tissue, so in addition to the studies involving the generation of articular cartilage from human stem cells, he and his team are trying different protocols using various combinations of adult progenitor cells present in the joint to regenerate cartilage until the best one is found for therapeutic use.

With the progenitor cells and the landmarks of proper cartilage development identified, Evseenko believes that an effective cellular therapy for diseased or damaged joint cartilage could be tested in human trials within three years. Such stem cell-based therapies could make many current knee and hip replacement surgeries unnecessary, offering patients the ability to regrow lost cartilage, keep their bones intact and avoid the discomfort and risk of major joint-replacement surgery.
-end-
The research was supported by the National Institutes of Health, the U.S. Department of Defense, the Arthritis National Research Fund and the California Institute of Regenerative Medicine.

The Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 200 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA's Jonsson Comprehensive Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science.

For more news, visit the UCLA Newsroom and follow us on Twitter.

University of California - Los Angeles

Related Stem Cells Articles from Brightsurf:

SUTD researchers create heart cells from stem cells using 3D printing
SUTD researchers 3D printed a micro-scaled physical device to demonstrate a new level of control in the directed differentiation of stem cells, enhancing the production of cardiomyocytes.

More selective elimination of leukemia stem cells and blood stem cells
Hematopoietic stem cells from a healthy donor can help patients suffering from acute leukemia.

Computer simulations visualize how DNA is recognized to convert cells into stem cells
Researchers of the Hubrecht Institute (KNAW - The Netherlands) and the Max Planck Institute in Münster (Germany) have revealed how an essential protein helps to activate genomic DNA during the conversion of regular adult human cells into stem cells.

First events in stem cells becoming specialized cells needed for organ development
Cell biologists at the University of Toronto shed light on the very first step stem cells go through to turn into the specialized cells that make up organs.

Surprising research result: All immature cells can develop into stem cells
New sensational study conducted at the University of Copenhagen disproves traditional knowledge of stem cell development.

The development of brain stem cells into new nerve cells and why this can lead to cancer
Stem cells are true Jacks-of-all-trades of our bodies, as they can turn into the many different cell types of all organs.

Healthy blood stem cells have as many DNA mutations as leukemic cells
Researchers from the Princess Máxima Center for Pediatric Oncology have shown that the number of mutations in healthy and leukemic blood stem cells does not differ.

New method grows brain cells from stem cells quickly and efficiently
Researchers at Lund University in Sweden have developed a faster method to generate functional brain cells, called astrocytes, from embryonic stem cells.

NUS researchers confine mature cells to turn them into stem cells
Recent research led by Professor G.V. Shivashankar of the Mechanobiology Institute at the National University of Singapore and the FIRC Institute of Molecular Oncology in Italy, has revealed that mature cells can be reprogrammed into re-deployable stem cells without direct genetic modification -- by confining them to a defined geometric space for an extended period of time.

Researchers develop a new method for turning skin cells into pluripotent stem cells
Researchers at the University of Helsinki, Finland, and Karolinska Institutet, Sweden, have for the first time succeeded in converting human skin cells into pluripotent stem cells by activating the cell's own genes.

Read More: Stem Cells News and Stem Cells Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.