Damaged bone or cartilage? Now, grow your own cells in a lab – Hindustan Times

When 14-year-old Aarav Gulati (name changed on request) met with an accident a couple of years ago while playing football, he injured his knee. A portion of the cartilage was damaged, and doctors used turned to a radical new procedure for a solution. They took Gulatis own cells, grew them in a lab and used them to replace the cartilage and repair the damage in a natural way.

He was an ideal case for the use of regenerative cell therapy that was a fairly new phenomenon in orthopaedic treatment in India, says Dr Yash Gulati, senior joint replacement and spine surgeon, New Delhis Indraprastha Apollo Hospital.

The regenerative cell therapy got US FDA approval this year, and the Apollo group partnered with RMS REGROW, a company that specialises in cell therapy technology, to exclusively offer the treatment to patients in India.

Instead of using artificial implants, the technique helps in healing the bone or cartilage damage in a natural way using a persons own cells to regain normal function. Cultured cells (grown in a lab) are injected into a patient to replace diseased or dysfunctional cells.

Instead of using artificial implants, the technique helps in healing the bone or cartilage damage in a natural way using a persons own cells to regain normal function. Cultured cells (grown in a lab) are injected into a patient to replace diseased or dysfunctional cells. (Illustration: Siddhant Jumde)

A small part of the joint cartilage is taken through a keyhole procedure, and is grown in a special manner to convert it into stem cells in the laboratory, says Dr Gulati. This is then applied on the area showing loss of joint cartilage.

Dr Gulati has so far treated 10 people using this therapy in Apollo, Delhi.

Stem cells lead to growth of joint cartilage in defective areas, and normal new cartilage re-grows. In bone damage, bone marrow cells are harvested, cultured and implanted in the area to be able to re-grow in a healthy way, Dr Gulati says.

In Mumbai, those in need of joint replacement because of injury, wear and tear or other lifestyle and ageing, are also realising that new cartilage can be grown in a lab from ones own cells and used instead of artificial materials.

Chondron or cartilage cell therapy is a patient-specific regenerative medical treatment which naturally regrows original cartilage. The therapy is used for repairing articular cartilage of the knee, ankle and shoulder joints and to help replace missing areas of cartilage.

This is a process where a biopsy of cartilage cells (chondrocytes) is taken from the patients knee, ankle or shoulder, says Satyen Sanghavi, chief scientific officer of Regenerative Medical Services Regrow, a biotechnology company in Mumbai.

Causes of bone or cartilage damage

They are then cultured to grow and multiply in a lab for 3-4 weeks into a surplus population of several million. The cultured cells are then re-implanted in the damaged area in a minimally invasive surgical procedure.

The process comes from eight years of work in cell and tissue therapy research. Chondron ACI is the countrys first cell therapy product.

These cells grow and repair tissue with properties similar to that of normal cartilage present in other joints, says Sanghavi. But replacement alone doesnt solve problems. Patients are expected to follow a rehabilitation program, to help the body adjust to new cells and them get back to day-to-day physical.

Its easy to see the advantages of a process like this. Experts say it may avoid the need for future prosthetic joints replacement (especially partial joint replacement) and allows patients the freedom to continue physical activities as before.

It also poses less risk of disease transmission or infection since it comes from the patients own tissue (no foreign material or metal goes inside the body). It may also halt further progression to osteoarthritis, a common problem with those in need of joint replacement.

The procedure costs Rs.3 to 3.5 lakhs.

In India, more than 500 patients have been treated with both bone and cartilage cell therapy procedures, says Sanghavi.

There is a success rate of more than 95%. During our clinical trials and research, we have treated working professionals, housewives, athletes, army men and mountaineers. Almost all of them have successfully recovered and got back to their active life.

However, this new technique has a flip side, too.

The price could be a bit steep for some because stem cell treatment is expensive; and the treatment gets prolonged as a patient has to wait for some time as cell culture takes time and one cannot bear weight on the affected area while the healing is on. Also, not all patients are suitable for it because it can correct only if damage isnt extensive, says Dr Ankit Goyal, associate professor, Safdarjung Sports Injury Centre (SIC) in Delhi.

Safdarjung Hospital had also treated about 35 patients, who had damaged their cartilage, with the technique a few years ago.

We would send cartilage for culture but only in cases where damage was limited. This is definitely not a substitute for knee or hip replacement procedure where the entire joint is extensively damaged. However, it may prevent the need for replacement later on in life, especially in young patients, he says.

More:
Damaged bone or cartilage? Now, grow your own cells in a lab - Hindustan Times

Scientists manipulate ‘signaling’ molecules to control cell migration – Phys.Org

June 30, 2017 Researchers have found a way to tweak cells' movement patterns to resemble those of other cell types. Credit: Tim Phelps/Johns Hopkins University

Johns Hopkins researchers report they have uncovered a mechanism in amoebae that rapidly changes the way cells migrate by resetting their sensitivity to the naturally occurring internal signaling events that drive such movement. The finding, described in a report published online March 28 in Nature Cell Biology, demonstrates that the migratory behavior of cells may be less "hard-wired" than previously thought, the researchers say, and advances the future possibility of finding ways to manipulate and control some deadly forms of cell migration, including cancer metastasis.

"In different tissues inside the body, cells adopt different ways to migrate, based on their genetic profile and environment," says Yuchuan Miao, a graduate student at the Johns Hopkins University School of Medicine and lead author of the study. "This gives them better efficiency to perform specific tasks." For example, white blood cells rhythmically extend small protrusions that allow them to squeeze through blood vessels, whereas skin cells glide, like moving "fans," to close wounds.

On the other hand, Miao notes, uncontrolled cell migration contributes to diseases, including cancer and atherosclerosis, the two leading causes of death in the United States. The migration of tumor cells to distant sites in the body, or metastasis, is what kills most cancer patients, and defective white blood cell migration causes atherosclerosis and inflammatory diseases, such as arthritis, which affects 54 million Americans and costs more than $125 billion annually in medical expenditures and lost earnings.

Because cells migrate in different ways, many drugs already designed to prevent migration work only narrowly and are rarely more than mildly effective, fueling the search for new strategies to control migratory switches and treat migration-related diseases, according to senior author Peter Devreotes, Ph.D., a professor and director of the Department of Cell Biology at the Johns Hopkins University School of Medicine's Institute for Basic Biomedical Research.

"People have thought that cells are typed by the way they look and migrate; our work shows that we can change the cell's migrating mode within minutes," adds Devreotes.

For the new study, Devreotes and his team focused on how chemical signaling molecules activate the motility machinery to generate protrusions, cellular "feet" that are a first step in migration. To do this, they engineered a strain of Dictyostelium discoideum, an amoeba that can move itself around in a manner similar to white blood cells. The engineered amoebae responded to the chemical rapamycin by rapidly moving the enzyme Inp54p to the cell surface, where it disrupted the signaling network. The cells also contained fluorescent proteins, or "markers," that lit up and showed researchers when and where signaling molecules were at work.

Experiments showed that the engineered cells changed their migration behavior within minutes of Inp54p recruitment. Some cells, which the researchers termed "oscillators," first extended protrusions all around the cell margins and then suddenly pulled them back again, moving in short spurts before repeating the cycle. Fluorescent markers showed that these cycles corresponded to alternating periods of total activation and inactivation, in contrast to the small bursts of activity seen in normal cells.

The video will load shortly

Other cells began to glide as "fans," with a broad zone of protrusions marked by persistent signaling activity.

Devreotes describes the signaling behavior at the cell surface as a series of waves of activated signaling molecules that switch on the cellular motility machinery as they spread. In their normal state, cells spontaneously initiated signaling events to form short-lived waves that made small protrusions.

In contrast, oscillators had faster signaling waves that reached the entire cell boundary to generate protrusions before dying out. Fans also showed expanded waves that continually activated the cell front without ever reaching the cell rear, resulting in wide, persistent protrusions.

The scientists say their experiments show that the cell movement changes they saw resulted from lowering the threshold level of signaling activity required to form a wave. That is, cells with a lower threshold are more likely to generate waves and, once initiated, the activation signals spread farther with each step.

Devreotes says the team's experimental results offer what appears to be the first direct evidence that waves of signaling molecules drive migratory behavior. Previously, his laboratory showed a link between signaling and migration, but had not specifically examined waves.

In further experiments, Devreotes and his team found that they could recruit different proteins to shift cell motility, suggesting, he says, that altering threshold is a general cell property that can change behaviorno matter how cells migrate. His team was also able to restore normal motility to fans and oscillators by blocking various signaling activities, suggesting new targets for drugs that could be designed to control migration.

Devreotes cautions that what happens in an amoeba may not have an exact counterpart in a human cell, but studies in his lab suggest that something like the wave-signaling mechanism they uncovered operates in human cells as well.

The bottom line, says Miao, is that "we now know we can change signaling wave behavior to control the types of protrusions cells make. When cells have different protrusions, they have different migratory modes. When we come to understand the essential differences between cells' migratory modes, we should have better ways to control them during disease conditions."

Explore further: How cells communicate to move together as a group

More information: Yuchuan Miao et al. Altering the threshold of an excitable signal transduction network changes cell migratory modes, Nature Cell Biology (2017). DOI: 10.1038/ncb3495

When an individual cell needs to move somewhere, it manages just fine on its own. It extends protrusions from its leading edge and retracts the trailing edge to scoot itself along, without having to worry about what the other ...

Cell migration is important for development and physiology of multicellular organisms. During embryonic development individual cells and cell clusters can move over relatively long distances, and cell migration is also essential ...

When Greek mythology and cell biology meet, you get the protein Callipygian, recently discovered and named by researchers at The Johns Hopkins University for its role in determining which area of a cell becomes the back as ...

(Medical Xpress) -- Discoveries by a Yale-led team of scientists could lead the way for development of new therapies for treating fibrosis and tumor metastasis. The researchers have both uncovered a signaling pathway that ...

Living cells respond to biochemical signals by moving toward those at higher concentration, a process carefully mapped out by biologists over the past several decades. But cells also move in response to mechanical forces, ...

This heart-shaped image shows two mouse skin cancer cells connected to each other with actin, a protein that is part of the cellular skeleton. Researchers use mouse cells like these to tease out the molecular methods that ...

Nature makes the vibrant pigments manufacturers want for foods and cosmetics, but getting them from plants to the products we buy is so difficult that many manufacturers rely on artificial colors. Now, researchers at Rensselaer ...

For centuries evolutionary biologists have been considering a difficult question: why do some animals 'choose' not to have children and instead help others rear their young? Researchers from Royal Holloway, University of ...

(Phys.org)A team of researchers at Purdue University in the U.S. and the University of Amsterdam and Universit catholique de Louvain in the Netherlands has isolated the gene responsible for producing a protein that aids ...

If cellular identity is to be maintained, it is important that actively transcribed chromatin stretches remain in a loose configuration as long as these genes are needed. Marc Bhler and his group have uncovered a novel ...

Johns Hopkins researchers report they have uncovered a mechanism in amoebae that rapidly changes the way cells migrate by resetting their sensitivity to the naturally occurring internal signaling events that drive such movement. ...

Photosynthesis is one of the most complicated and important processesresponsible for kick-starting Earth's food chain. While we have modeled its more-than-100 major steps, scientists are still discovering the purpose of ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

See original here:
Scientists manipulate 'signaling' molecules to control cell migration - Phys.Org