Stem Cell Clinic

Amazing medicine – The News International

If we cut off the tail of a lizard, it grows back. If we cut off the hand of a human being, it does not grow back. Why not? This question has perplexed scientists for a long time. Recently scientists at the Translational Genomics Research Institute (TGen) and Arizona State University (ASU) in the US identified three tiny RNA switches (known as microRNAs) which turn genes on and off and are responsible for the regeneration of tails in the green lizard. Now researchers are hoping that using the next generation genomic DNA and computer analysis will lead to discoveries of new therapeutic approaches to switch on similar regenerative genes in human beings.

Micro RNAs are able to control many genes at the same time. They have been compared to an orchestra conductor controlling and directing many musicians. Hundreds of genes (musicians playing the orchestra of life), controlled by a few micro RNA switches, have been identified that are responsible in the regenerative process. This may well mark the beginning of a new era in which it may be possible to regenerate cartilage in knees, repair spinal cords and amputated limbs.

Tissue regeneration has become an attractive field of science, triggered by exciting advances in stem cell technologies. Stem cells are undifferentiated biological cells that are then converted into various types of cells such as heart, kidney or skin through a process known as differentiation. They can divide into more stem cells and provide a very effective mechanism for repair of damaged tissues in the body. The developing embryo contains stem cells which are then transformed into specialised cells as the embryo develops. They can be obtained by extraction from the bone marrow, adipose tissue or blood, particularly the blood from the umblical cord after birth.

Stem cells are now finding use in a growing number of therapies. For instance leukaemia is a cancer of the white blood cells. To treat leukaemia, one approach is to get rid of the diseased white blood cells and replace them with healthy cells. This may be done by a bone marrow transplant through which the patients bone marrow stem cells are replaced with those from a healthy, matching donor. If the transplant is successful, the stem cells migrate into the patients bone marrow resulting in the production of new, healthy white blood cells that replace the abnormal cells. Stem cells can now be artificially grown and then transformed (differentiated) into the heart, kidney, nerve or other typed of cells.

The field of regenerative medicine is developing at a fast pace. It involves the replacement, engineering or regeneration of human tissues and organs so that their normal function can be restored. Tissues and organs can also be grown in the laboratory if the body cannot heal itself. If the cells of the organ being grown are derived from the patients own cells, the possibility of rejection of the transplanted organ is minimised. Stem cells may also be used to regenerate organs.

Each year about 130,000 organs, mostly kidneys, are transplanted from one human being to another. The process of growing organs artificially has been greatly accelerated by the advent of 3D bioprinting. This involves the use of 3D printing technologies through which a human organ, liver or kidney, is produced by printing it with cells, layer-by-layer. This became possible when it was discovered that human cells can be sprayed through the nozzles of an inkjet printer without destroying or damaging them. Tissues and organs can thus be produced and transplanted into humans. Joints, jaw bones and ligaments can also be produced in this manner.

Initially, the work was confined to animals when ears, bones and muscle tissues were produced by bioprinting and then successfully transplanted into animals. Even prosthetic ovaries of mice were produced and transplanted so that the recipient mice could conceive and give birth later. While gonads have not been produced by bioprinting in humans, blood vessels have already been produced by the printing process and successfully transplanted into monkeys. Considerable work is also going on in the production of human knee cartilage pads through the bioprinting process. Wear and tear of the cartilage results in difficulties in walking, particular in older age groups, and often requires knee replacement through surgeries. The development of technologies to replace the damaged cartilages with new cartilages made by bioprinting could prove to be invaluable.

Another area of active research in this field is the production of human skin by bioprinting which may be used for treating burns and ulcers. Technologies have been developed to spray stem cells derived from the patient directly on the areas of the body where the skin is needed. In this way, stem cells help skin cells regrow under suitable conditions. Similar progress is being made in generating liver, kidney and heart tissues so that the long waiting time for donors can be circumvented.

When will we be able to print entire human organs? It has been estimated that complete human kidneys and livers should become commercially available through the bioprinting process within five to seven years. Hearts will probably take longer because of their more complex internal structure. However, one thing is clear: a huge revolution is now taking place in the field of regenerative medicine, triggered by spectacular advances in stem cell research. This presents a wonderful opportunity for learning and developing expertise in this field for us in our country.

In Pakistan a number of important steps have been taken in this fast evolving field. One of them is the establishment of a first rate facility for stem cell research in the Dr Panjwani Centre for Molecular Medicine and Drug Research (PCMD) in the University of Karachi. This institution has already earned an international reputation because of its outstanding publications in this field.

A second important development is that plans to set up an Institute for Translational Regenerative Medicine at PCMD so that Pakistan remains at the cutting edge in this fast emerging field are now under way.

Such initiatives can however only contribute to the process of socio-economic development if they operate under an ecosystem that is designed to promote the establishment of a strong knowledge economy.

Pakistan spends only about 0.3 percent of its GDP on science and about two percent of its GDP on education, bringing the nations ranking to the lowest 10 countries in the world. This is largely due to the stranglehold of the feudal system over our democracy. It is only by tapping into our real wealth our children that Pakistan can emerge from the quagmire of illiteracy and poverty and stand with dignity in the comity of nations.

The writer is chairman of UN ESCAP Committee on Science Technology & Innovation and former chairman of the HEC. Email: [emailprotected]

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Amazing medicine - The News International

T cells support long-lived antibody-producing cells – Medical Xpress

February 21, 2017 by Katherine Unger Baillie Long-lived plasma cells (yellow) dwell in the bone marrow. Credit: University of Pennsylvania

If you've ever wondered how a vaccine given decades ago can still protect against infection, you have your plasma cells to thank. Plasma cells are long-lived B cells that reside in the bone marrow and churn out antibodies against previously encountered vaccines or pathogens.

While plasma cells are vital components of the immune system, they can also be a contributor to disease, as is the case in autoimmune diseases, such as lupus and rheumatoid arthritis, and in certain cancers, such as multiple myeloma.

Now, a group led by researchers at the University of Pennsylvania School of Veterinary Medicine, has come to a better understanding of how these cells are maintained. Using a specialized type of microscope that captures the movement and interaction of cells in living organisms, the scientists observed that, in the bone marrow, immune cells called regulatory T cells closely interact with plasma cells and support them. When the T cells aren't there, plasma cells vanish.

"This interaction was completely unanticipated," said senior author Christopher A. Hunter, Mindy Halikman Heyer Distinguished Professor of Pathobiology and chair of the Department of Pathobiology at Penn Vet. "If we can understand what controls these long-lived plasma cells, then maybe we can augment that interaction, making more plasma cells to, for example, enhance vaccine efficiency. Or, if you want to limit autoimmunity or cancer, maybe there is an opportunity to disrupt this niche to mitigate some of those conditions."

The research, published in the journal Cell Reports, was led by two trainees in Hunter's laboratory, Arielle Glatman Zaretsky and Christoph Konradt, along with a team of researchers from Penn Vet, Penn's Perelman School of Medicine, Harvard Medical School, Osaka University, Medimmune, the University of California, San Diego, and The Wistar Institute.

Hunter's laboratory has long investigated how the immune system responds to infection with the parasite Toxoplasma gondii. They have used high-tech microscopy to visualize the dynamics of immune cells and other structures in living organisms.

This specialized imaging was able to turn up a surprising finding. A video of the bone marrow in a mouse exposed to T. gondii revealed that the animal's plasma cells disappeared, later returning as the infection was controlled.

A few other groups had seen plasma cells behave similarly in response to systemic inflammation or infection, but the reason for the drop in plasma cells remained unclear.

"We don't know whether these cells leave the bone marrow or die there during infection, but, either way, they are gone," said Glatman Zaretzky. "And that set up a great system to understand what kinds of cellular interactions normally create the hospitable environment and allow the plasma cells to remain there."

The research team had noticed that regulatory T cells, which Hunter calls "the health and safety inspectors" of the immune system because they keep immune responses at the appropriate level, were located in a similar region of the bone marrow as the plasma cells, next to the blood vessels. And, when mice were exposed to an infection, these "T regs" declined precipitously, just as the plasma cells had.

Together, these observations called to mind an earlier finding by another group of scientists that showed that T regs play a key role in protecting the bone marrow from inflammation. In other words, it suggested that T regs make the bone marrow an immune-privileged site, shielding its vital components from the potentially damaging effects of infection or immune response.

Curious whether these T regs interacted with plasma cells, the researchers examined both cell types in mice that have T regs labeled with a green fluorescent marker and plasma cells labeled with a yellow one. They found that T regs appeared to be closely interacting with plasma cells for extended periods of time.

"No one had put these two cell types together before," Hunter said. "Yet, when we looked, we saw that these interactions were not rare but were frequent and sustained."

Further studies found that both of these cell types also interact with dendritic cells, which are thought to promote plasma-cell survival. The researchers also demonstrated that T regs were necessary to maintain plasma cells, showing that enhancing T reg survival in mice during infection increased plasma-cell numbers and that experimentally depleting T regs led to reductions in plasma cells.

The work gives insight into how the body is able to sustain plasma cells for so long, ensuring that they will jump into action even years after a vaccine was administered or an earlier infection was conquered. They also lay the foundation for targeting this cell populationa feat that has thus far escaped scientiststo ameliorate autoimmune diseases that arise due to inappropriate antibody production or to treat cancers that form from plasma cells.

Explore further: Shp1 protein helps immune system develop its long-term memory

More information: Cell Reports, DOI: 10.1016/j.celrep.2017.01.067 , http://www.cell.com/cell-reports/fulltext/S2211-1247(17)30137-7

A protein called Shp1 is vital to the immune system's ability to remember infections and fight them off when they reappear, researchers at A*STAR have found.

Antibody-secreting plasma cells arise from B cell precursors and are essential for adaptive immune responses against invading pathogens. Plasma cell dysfunction is associated with autoimmune and neoplastic disorders, including ...

Melbourne researchers have identified a protein responsible for preserving the antibody-producing cells that lead to long-term immunity after infection or vaccination.

Multiple myeloma is a cancer of the plasma cells that reside inside bone marrow. Plasma cells produce certain proteins that build up the immune system. In abnormal quantities, these proteins damage the body and compromise ...

Scientists have identified the gene essential for survival of antibody-producing cells, a finding that could lead to better treatments for diseases where these cells are out of control, such as myeloma and chronic immune ...

Scientists from A*STAR's Bioprocessing Technology Institute (BTI) have uncovered the crucial role of two signalling molecules, DOK3 and SHP1, in the development and production of plasma cells. These discoveries, published ...

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T cells support long-lived antibody-producing cells - Medical Xpress

Hear This: Scientists Regrow Sound-Sensing Cells – Live Science

Scientists have coaxed sound-sensing cells in the ear, called "hair cells," to grow from stem cells. This technique, if perfected with human cells, could help halt or reverse the most common form of hearing loss, according to a new study.

These delicate hair cells can be damaged by excessive noise, ear infections, certain medicines or the natural process of aging. Human hair cells do not naturally regenerate; so as they die, hearing declines.

More than 20 million Americans have significant hearing loss resulting from the death or injury of these sensory hair cells, accounting for about 90 percent of hearing loss in the United States, according to the Centers for Disease Control and Prevention.

In the new study, scientists at Harvard University and the Massachusetts Institute of Technology reported that they isolated stem cells from a mouse ear, discovered how to get them to multiply in a laboratory setting, and then converted them into hair cells. Their previous efforts, in 2013, produced only 200 hair cells. With a new technique, however, the research team has increased this number to 11,500 hair cells that were grown from one mouse ear. [Inside Life Science: Once Upon a Stem Cell]

Their paper describing the stem cell advance appears today (Feb. 21) in the journal Cell Reports.

Jeffrey Corwin, an expert on hair-cell regeneration and a professor of neuroscience at the University of Virginia School of Medicine, who was not part of this new research, called it "a very impressive studyby a dream team of scientists" and "a big advance" in the pursuit of regenerating these sensory hearing cells in humans.

Hair cells grow in bundles in the inner ear, and are so named because they look like hairs. Many hair cells within the ear are involved in balance, not hearing. But in the cochlea, the hearing organ deep in the ear canal, there are two kinds of specialized hair cells: outer hair cells, which amplify pitch and enable humans to discern subtle differences in sound; and inner hair cells, which convert sound into electrical signals sent to the brain. Humans have two cochleae (one in each ear), and each has only about 16,000 hair cells.

In fish, birds, lizards and amphibians, cochlear hair cells that die can be regenerated in as fast as a few days. However, in mammals, for the most part, the cells cannot regenerate except for mice and other small mammals when they are newly born. But since so many species can naturally regenerate hair cells from a stem cell precursor, including some newborn mammals, many researchers have been motivated to find a way to rekindle hair-cell regeneration in adult mammals and, of course, in humans, Corwin said.

The new research was done by a team led by Albert Edge, director of the Tillotson Cell Biology Unit at the Massachusetts Eye and Ear Infirmary and professor of otolaryngology at Harvard Medical School in Boston.

In 2012, Edge's group discovered stem cells in the ear called Lgr5+ cells. These cells are also found in the gut, where they actively regenerate the entire lining of human intestines every eight days. The research team soon found a way to coax the Lgr5+ cells to differentiate into hair cells, instead of intestinal cells. But the process was slow, and the yield was low.

Now, the researchers have increased the yield dramatically by inserting a new step. After removing Lgr5+ cells from mice, the researchers first get them to divide in a special growth medium. This step produced a two-thousandfold increase in Lgr5+ cells, Edge told Live Science. Then, the researchers moved these stem cells into a different kind of growth culture and added certain chemicals to turn the Lgr5+ cells into hair cells. [7 Ways the Mind and Body Change With Age]

These laboratory-grown hair cells appear to have many of the characteristics of actual inner and outer hair cells, although they might not be fully functional, Edge said. The most immediate use for this new technique will be to create a large set of the cells to test drugs and to identify compounds that can heal damaged hair cells or regrow them and restore hearing, Edge said.

Scientists have had difficulty testing drugs on large batches of actual hair cells because there are so few in mammalian ears and they are deep in the cochlea, hard to extract, Edge said.

The researchers have reason to believe the technique to regenerate fully functional hair cells in humans could someday work. As reported in their paper, the team tested the technique on a sample of healthy ear tissue from a 40-year-old patient who underwent a labyrinthectomy (removal of parts of the inner ear) to access a brain tumor. The adult human stem cells isolated from this tissue also multiplied and differentiated into hair cells, although not as robustly as the mouse cells did.

But as Corwin noted about Edge's research, "You can see in their paper that they are perfecting their technique as they go along."

Follow Christopher Wanjek @wanjekfor daily tweets on health and science with a humorous edge. Wanjek is the author of "Food at Work" and "Bad Medicine." His column, Bad Medicine, appears regularly on Live Science.

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Hear This: Scientists Regrow Sound-Sensing Cells - Live Science

Stem cell therapy adds pep to pets – Liberty Tribune

COLUMBUS For the past year, Dr. Todd Paczosa has been practicing what he calls the future of medicine.

The veterinarian treats his four-legged patients through stem cell therapy.

Im not anti-antibiotic, anti-medicine. I just believe that even in the future of cancer treatment that it is going to come down to your body healing itself, Paczosa said.

The process involves removing fatty tissue from a patient, extracting stem cells, then injecting the cells back into the animal's joints to promote healing.

Paczosa said he researched the treatment for about a decade before deciding to offer it at Redstone Veterinary Hospital in Columbus.

Our body is full of cells that heal. You get cut, your body heals. What we are doing is taking those cells, waking them up and saying, Hey, lets go to work, he said.

Since he started offering stem cell therapy last March, 17 dogs, horses and cattle have used the treatment. One of those patients is Butch, a 9-year-old schnauzer owned by Marge Biester of Columbus that was suffering from a strained ligament and achy joints.

He was really hurting. I had to do something for him, Biester said, adding that Butch wasnt putting much weight on his back leg when he walked.

The treatment was done in January. Butch was put under anesthesia to retrieve the fat tissue. Using equipment in-house, the stem cells were extracted and injected back into the dog that same day.

Paczosa, who has been a veterinarian for 23 years, said the entire process can be done in a day.

Biester noticed results in about two weeks.Butch wasnt doing his three-legged walk anymore and began acting like a more-active, younger version of himself.

Im amazed at how quickly he recovered, she said.

Paczosa said all of the animals he has treated so far have shown improvement.

One of these days, we will have one that doesnt work. Thats just medicine, but we havent had one yet, he said.

The possibility of the stem cell therapy not working can be a turnoff for some pet owners who might find it difficult to spend $1,900 to $2,400 for the treatment at Redstone. If it does work, Paczosa said the therapy is less expensive in the long run than putting an animal on medication for extended periods of time to ease the pain from arthritis.

Other pluses, he said, are that the regenerative therapy isnt as invasive as surgery and anti-rejection drugs don't have to be used since the cells come from the same animal.More than one joint can also be treated at a time and it can eliminate the use of non-steroidal anti-inflammatory drugs.

The biggest risks are putting the animal under anesthesia and infection of the surgical site where the fatty tissue is removed, typically from the shoulder area or abdomen.

Stem cell therapy is practiced at a few hundred veterinary clinics in the country. Redstone works with the animal stem cell company MediVet Biologics and uses that companys in-house technology.

Paczosa said owners have come from other states to use the therapy at his Columbus clinic.

Initial results from the procedure lasts about two years. An option to bank stem cells from a pet is available. A portion of what is taken can be stored in a lab and used again in the future.

For Paczosa's patients, results have been quick and ongoing.

Most owners have seen a dramatic improvement in two weeks. Our first patient is still seeing improvements, he said.

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Stem cell therapy adds pep to pets - Liberty Tribune

TiGenix hires Lonza to make cell therapy for Crohn’s complications – BioPharma-Reporter.com

TiGenix is using Lonza as a US CMO and Takeda as an ex-US commercialization partner to launch and trial its off-the-shelf stem cell therapy for a complication of Crohns disease.

TiGenix NV is a Belgian biotech developing a Phase III cell therapy Cx601 for a complication of Crohns Disease which has been licensed ex-US to Takeda Pharmaceutical Company Ltd.

Cx601 is based on stem cells taken from donor adipose tissue, as an allogenic off-the-shelf cell therapy product for the treatment of complex perianal fistulas in patients with Crohns disease patients who do not otherwise respond to standard therapies.

According to new data released today from thepivotal Phase III trial , Cx601 has reached its primary endpoint: long term remission ofperianal fistulas in patients with Crohns disease.

Wilfried Dalemans, CTO of TiGenix, told Biopharma-Reporter that TiGenix is also working with Lonza to facilitate a new trial for registering Cx601 in the states.

[Lonza] is now introducing our manufacturing process into their facilities in the US. Once the tech transfer is completed, they will produce clinical material,he told us.

TiGenix is developing Cx601 in the States after an agreement with the US FDA based on a special protocol assessment procedure (SPA) in 2015. Dalemans added:This is the first time we're working with a CMO in the US.

For the pivotal Phase III trial for Cx601 in the US, TiGenix will use the services of a US-based contract manufacturing organization, Lonza. This trial is expected to begin in the first half of 2017, and the firm has already begun the process of transferring our technology to them for the purpose to this trial.

Manufacturing Cx601

The Cx601 therapies are manufactured in a 2-dimensional cell culture in CF5, and according to Dalemans, do not yet need more sophisticated reactors.

To meet the manufacturing capacity for the European launch of Cx601, the current GMP facilities in Madrid are currently being expanded with the 50-50 financial support of Takeda.

Dalemans told us:We're using local service providers for the engineering of the facility extension. For the equipment, we are at this stage still selecting who we will use to supply instruments like incubators and laminar flows etc.

From the manufacturing site, the products arepackaged in special containers to maintain a temperature between 15 25 degrees centigrade for transport to the clinical site.

Cx601 is a living product - a suspension of living cells kept at room temperature. Because its not a frozen product, we do indeed need a cold chain supplier,he explained.

Takedas advice

Last July last year TiGenix partnered with Takeda to give the big pharma firm exclusive rights to commercialize Cx601 for complex perianal fistulas outside the US.

Luke Willats, a spokesperson for Takeda, told us:Takeda is a global leader in gastroenterology, [so] the acquisition of Cx601 is just a dedication and commitment to GI - and the related complications.

For these reasons, Takeda and TiGenix are working very closely in anticipation of the EMA approval, expected in the second half of 2017.

Dalemans explained: We're expanding our current Madrid facility to meet the capacity that will be needed once Takeda begins to commercialise Cx601 - we're also working closely with Takeda for even further extension of the capacity.

Willats told us that once authorization by the European regulators is obtained, Takeda will assume commercialization for Cx601 outside of the US.

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TiGenix hires Lonza to make cell therapy for Crohn's complications - BioPharma-Reporter.com