Category Archives: Cell Therapy

Q: I read that you can use your own stem cells to rejuvenate worn-out knees. Does this really work?

A: Worn out is a good way to term what happens to the knee joint with prolonged use. Lets look at how this happens, starting with cartilage.

The lower portion of the knee joint (at the tibia) contains shock absorbers called menisci made of cartilage. You have one on the inner portion and another on the outer portion of each knee. The upper portion of the knee joint (at the femur) is lined with cartilage as well. All of this cartilage helps protect the bones at the joint but it doesnt heal or regenerate well due to limited blood supply. When severe, worn cartilage leads to arthritis of the knee. In knee X-rays of people over age 60, 37 percent have shown evidence of arthritis of the knees.

The intriguing thing about stem cells is that they have the ability to become any type of cell that the body needs. The cells used for stem cell injections in the knees are called mesenchymal stem cells, and they can differentiate into bone, fat or cartilage cells. These stem cells can come from the fat cells of your body, from your bone marrow or from the inner lining of your knee joint; theyre then replicated in the laboratory and injected into the knee joint.

Heres what the research shows so far.

In a 2013 study, 32 patients with meniscal tears of the knee were injected with a combination of stem cells, platelet-rich plasma and hyaluronic acid. The study reported improved symptoms and even MRI evidence of meniscal cartilage regeneration.

In a 2014 study, 55 patients who had surgery for meniscal tears of the knees were separated into three groups, with two of the groups receiving stem cell injections. Researchers found that, after six weeks, pain had decreased substantially in the two groups that received stem cell injections and that the decrease was even greater at one and two years after the injection.

In a 2017 study in the British Journal of Sports Medicine, researchers analyzed six studies that used stem cells for osteoarthritis of the knees. In five of the studies, stem cells were given after surgery to the knee; in the other study, stem cells from a donor were administered without surgery. All the studies showed reduced pain and improved knee function. Further, in three of the four trials, MRIs corroborated the cartilage improvements.

There may be benefit to stem cell injections for cartilage loss of the knees, but more data are needed. Id also like to see more data on this type of therapy as a preventive measure for younger patients before their knees are worn out.

ASK THE DOCTORS is written by Robert Ashley, M.D., Eve Glazier, M.D., and Elizabeth Ko, M.D. Send questions to askthedoctors@

mednet.ucla.edu, or write: Ask the Doctors, c/o Media Relations, UCLA Health, 924 Westwood Blvd., Suite 350, Los Angeles, CA, 90095.

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Stem cell therapy may help knees - News - Citizens' Voice - Citizens Voice

CAR T-cell immunotherapy was seen to eradicate or shrink tumors in 70% of patients with chronic lymphocytic leukemia (CLL) who had exhausted other treatment options, according to a clinical trial report.

Among those who had no sign of cancer left in the bone marrow four weeks after treatment, all had survived with no signs of cancer after six months.

Researchers at the Fred Hutchinson Cancer Research Center also suggested, based on the studies, that analyzing bone marrow using a new genetic technique is a better method than the more commonly used cell counts when attempting to determine a prognosis for the disease.

The report,Durable Molecular Remissions in Chronic Lymphocytic Leukemia Treated With CD19-Specific Chimeric Antigen ReceptorModified T Cells After Failure of Ibrutinib,described the outcomes of 24 CLL patients whose cancer had progressed after treatment with Imbruvica (ibrutinib), which was approved for the treatment of CLL in 2014. The research was published in theJournal of Clinical Oncology.

It was not known whether CAR T-cells could be used to treat these high-risk CLL patients, Cameron Turtle, an immunotherapy researcher at Fred Hutch and lead author of the study, said in apress release. Our study shows that CD19 CAR T-cells are a highly promising treatment for CLL patients who have failed ibrutinib.

CD19 is a molecule found on the surface of leukemia cells. T-cells, gathered from a patient, are engineered to specifically recognize this factor. When that happens, the body launches an aggressive immune response toward these cancer cells.

The Phase 1/2 study (NCT01865617) which is still recruiting participants included patients who had failed a median of five previous treatment rounds. The participants ages ranged from 40 to 73.

Before injecting the engineered T-cells into patients, their white blood cells were destroyed by chemotherapy.

One patient had a severe toxic response to the treatment and was not assessed for the therapys effects. Among the remaining patients, 16 of 23 70% had a response four weeks after treatment.

Not all patients had chemotherapy before CAR T-cell treatment, but among the 19 who did, four had a complete response, and 10 had a partial response.

Two additional patients responded after a second round of chemotherapy and CAR T-cell treatment.

Analyzing bone marrow using a method that can sort cancerous cells from normal cells indicated that 88% were free of disease after treatment. But repeating the analysis in 12 of these patients using a method called IGH deep sequencing showed that only 58% of them had no disease present in the bone marrow.

Those in which the genetic analysis found no traces of cancer all survived with no further traces of disease for a median of 6.6 months after treatment.

For more information about the trial, which also includes patients with relapsed or refractory non-Hodgkins lymphoma or acute lymphoblastic leukemia, see the trial registration page at thislink. The trial treats patients at theSeattle Cancer Care Allianceclinic.

More:
CAR T-Cell Therapy Shown to Eliminate Tumors in Some Chronic Lymphocytic Leukemia Patients During Trial - Lymphoma News Today

The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats' fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

"It's extremely exciting," said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing "the systemic rejuvenating effects," he said, "it's kind of like an unexpected fountain of youth."

"We've been studying new forms of cell therapy for the heart for some 12 years now," Marbn said.

Some of this research has focused on cardiosphere-derived cells.

"They're progenitor cells from the heart itself," Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem "that's very typical of what we find in older human beings: The heart's stiff, and it doesn't relax right, and it causes fluid to back up some," Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats -- that's elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

"The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I'm kind of losing my hair) the animals ... regrew their fur a lot better after they'd gotten cells" compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that "contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue," Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he's begun to explore delivering the cardiac stem cells intravenously in a simple infusion -- instead of injecting them directly into the heart, which would be a complex procedure for a human patient -- and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is "very comprehensive."

"Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems," said Gerstenblith, who did not contribute to the new research. "The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly."

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center's Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has "led the field in this area."

"The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they've seen in the past," said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells "from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue," Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

"We need to make sure there's no harm being done," Herron said, adding that extending the lifetime and improving quality of life amounts to "a tradeoff between the potential risk and the potential good that can be done."

Capicor hasn't announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven "completely safe" in "over 100 human patients," so it would be possible to fast-track them into the clinic, Marbn explained: "I can't tell you that there are any plans to do that, but it could easily be done from a safety viewpoint."

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Cardiac stem cells rejuvenate rats' aging hearts, study says - CNN - CNN

A leading gene and cell therapy group has announced a collaboration focusing on gene and cell therapy manufacturing..

A leading gene and cell therapy group, has announced it has agreed to enter into a collaboration agreement with a consortium of partners, the agreement is a two-year 2 million collaboration project focused on gene and cell therapy manufacturing, co-funded by the UKs innovation agency, Innovate UK.

Cell and gene therapies offer unprecedented promise for the cure, treatment or long-term management of disease and we are delighted that this consortium has been awarded funding from Innovate UK that will help to keep Oxford BioMedica (OXB), our partners and the UK, at the forefront of innovation in industrial viral vector manufacturing., said John Dawson, Chief Executive Officer of Oxford BioMedica.

The aim of the collaboration is to explore and apply novel advanced technologies to further evolve OXBs proprietary suspension LentiVector platform to deliver even higher quality vectors for both clinical and commercial use. The project aims to deliver tangible benefits to patients by shortening the time-to-clinic and time-to-market as well as to improve the cost and access of bringing novel gene and cell therapies to patients.

Each partner in the collaboration holds proprietary technology and know-how that can be used to develop an innovative approach to viral vector manufacturing.

Collaborating on developing improved process analytic technologies with our partners will help drive productivity in viral vector manufacturing, accelerating the development of these transformative advanced therapies. We have the opportunity to both transform patients lives and grow an industry in the UK that we can be proud of,said Keith Thompson, Chief Executive Officer of Cell and Gene Therapy Catapult.

The aims of this pioneering project are closely aligned with the current government national priorities to make the UK a global hub for manufacturing advanced therapies, which will benefit economic growth and create and retain more highly skilled employment.

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2m collaboration to focus on gene and cell therapy - Drug Target Review

An Odessa physician who specializes in pain management has begun offering stem cell therapy for inflammation from a variety of arthritis.

Dr. Mandeep Othee of ProCare Interventional Pain Medicine, said stem cell therapy has been around since as early as 1938. It has recently been used to stem inflammation, wound care and post-surgical use to help in healing.

The purpose for me is going to be for inflammation for knee arthritis, shoulder arthritis any sort of arthritic process in the neck, the back; any part of the body, Othee said.

Othee said hes always interested in cutting-edge treatments. As associate medical director of In-Patient Rehabilitation at Medical Center Hospital, Othee oversees care for patients with a variety of orthopedic needs, ranging from stroke patients to those recovering from joint replacement surgery, the hospital website said.

He also specializes in diagnosing and treating neck and low-back pain.

The source of the amniotic stem cells is healthy women who have had C-sections who donate their amniotic fluid to a tissue bank. Othee said it is fully regulated by the U.S. Food and Drug Administration and the cells are purified and frozen to preserve them.

The cells provide cushioning, support and lubrication to a developing fetus in the womb.

Its a similar process in the body, so for example, if we take that same stem cell and inject it into the patients knee, or shoulder, or back, or neck it provides the same cushioning, support, lubrication and inflammation reduction that it does in the developing fetus, Othee said.

He added that there are 226 growth factors in the fluid itself, which includes proteins, lipids electrolytes and the magic element of hyaluronic acid.

Thats the typical injection a patient receives in an orthopedic surgeons office. It basically heals the area, provides collagen synthesis and helps with the re-growth of that lost cartilage , Othee said.

Cartilage wears down over time in the joints and injecting the stem cells greatly increases the patients own healing response. Othee said it works 100,000 times better than Platelet Rich Plasma, which is taking a patients own platelets, spinning it down, putting it into a concentrated format and injecting into the patients knee, shoulder, neck or back, Othee said.

Typically, Othee said hes read studies have shown 30, 90 and 100-day responses that are better than steroid shots or hyaluronic acid injections.

It can help patients avoid or delay joint replacement surgeries.

The product he chose is OrthoFlo made by MiMedx.

I chose them because theyre the biggest and the best, Othee said. Their company specializes in different products. One is OrthoFlo. It contains pro-growth factors (and) no tissue fragments or dead cells. It is highly purified human amniotic fluid.

He noted that thousands of injections have been administered over the last five to 15 years and no reactions, side effects or infections have been reported that hes read about.

Currently, no insurance companies pay for the stem cell therapy, but athletes have been getting these for years in other countries, such as Germany and England, and larger cities such as Houston and Dallas. The cost is $2,200 per injection from Othee.

The patient may be sore for a day or two after the stem cell injection and they are able to walk out of the office without a problem. For any sort of knee injections, Othee said a patient may want to wait a week to start running or doing other activities.

Othee said he usually asks patients to stop taking anti-inflammatory medicine for at least seven days before and after the treatment.

He added that there is no age limit on people who could receive stem cell therapy.

Othee said patients may have tried steroid shots, hyaluronic acid, or platelet rich plasma before stem cell therapy. However, they could skip right to stem cell therapy, he added.

Othee said he has spoken to other doctors with patients who have gone straight to stem cell therapy and it works.

Orthopedic surgeon Dr. Vijay Borra doesnt do stem cell injections. He said he thinks research into stem cells just as an injection for osteoarthritis is still in its infancy.

I think a lot of research now is going into using stem cells to generate chondrocytes, which are cartilage to see if we can plug in focal cartilage deficits. Thats where all the research is now. As far as just injecting stem cells into the joint, were still at the very early stages and theres still very little data as to whether it actually works or not, Borra said.

Borra added that there is a lot of good data using that to generate cartilage.

Theres some data there can be used to plug defects. Its an option for people who have done everything like a steroid or hyaluronic gel injections. Theyve done all that and they dont want a knee replacement, or they have too many medical issues and theyre not a candidate. Then it is an option. If theres nothing else, then stem cell is an option, Borra said.

He added that stem cell therapy is not covered by most insurance plans and the out-of-pocket pay is very high.

Its really like an end-stage resort for someone who doesnt want surgery. Theres really no down side. Its not going to do any damage, so you can always try to see if it helps, Borra said.

When patients come to see him, Borra said he first gives them an x-ray to see what the problem is. Most of the time, its osteoarthritis.

By the time they come to Borra, he said the patient has tried anti-inflammatories, weight loss and therapy.

Theyve already done all that, so I start off with a steroid injection. If it works five, six months some people choose to do two or three a year. If it doesnt work, the next option is gel injections, hyaluronic acid, which is like artificial joint fluid, Borra said.

He said Othee also offers nerve blocks.

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Odessa physician offering stem cell therapy - Odessa American: News - Odessa American

medwireNews: Treatment with autologous chimeric antigen receptor (CAR) T cells directed against the epidermal growth factor receptor variant III (EGFRvIII) mutation is feasible and well tolerated in patients with recurrent glioblastoma, indicates a first-in-human study.

But barriers to the clinical efficacy of the therapy exist, says the research team, including the inhibitory tumor microenvironment, which becomes even more immunosuppressive after CAR T cells.

Lead author Marcela Maus (Massachusetts General Hospital, Boston, USA) and colleagues chose the EGFRvIII mutation as it is a tumor-specific, oncogenic, and immunogenic epitope expressed in around 30% of newly diagnosed cases of glioblastoma.

In this phase I study, reported in Science Translational Medicine, 10 patients with EGFRvIII-expressing glioblastoma that had progressed after at least one prior line of therapy were given a single infusion of an autologous EGFRvIII-directed CAR T product within a week of progression.

There were no dose-limiting toxicities, and no evidence of off-target EGFR-directed effects such as rash, diarrhea, or pulmonary symptoms or systemic cytokine release syndrome.

Neurologic events were observed in three patients and included a seizure at day 9 in one patient and neurologic decline in two patients, at day 15 in one case and postoperatively in the other. Although such events are common in glioblastoma patients due to the nature of the disease, Maus et al say that they could also result from CAR T-induced immune responses in the confined intracranial space.

They were unable to formally assess efficacy as the majority (n=7) of study participants underwent surgery following infusion of the CAR T cells. But one patient was alive and required no further treatment for 18months or more after the infusion. A further two patients were also alive at the time of analysis, but they showed signs of disease progression by imaging criteria.

The surgical intervention allowed the researchers to evaluate not only tissue-specific trafficking of CAR T cells and on-target effects, but also the tumor microenvironment in situ.

Analysis of tumor samples showed the presence of EGFRvIIICAR T cells in the brain, with higher levels in the four patients who had surgery within 14days of the infusion than in the three who underwent surgery at later timepoints.

And comparison of post-infusion samples with matched samples obtained before the infusion revealed a significant decline in the expression levels of EGFRvIII in five of the seven participants with available samples. Such a decrease in antigen expression in the remaining tumor bed and tissue is indicative of on-target effects, say Maus and colleagues.

But they also found that the expression of several immunosuppressive molecules, including indoleamine 2,3-dioxygenase 1, was markedly increased in post- versus pre-infusion samples, and noted elevations in the relative proportion of immunosuppressive FoxP3+ regulatory T cells after infusion.

These findings suggest that CART-EGFRvIII activation induced a compensatory multifactorial immunosuppressive response in situ, say the investigators, adding that it could potentially be overcome with existing drugs that target immunosuppressive molecules.

Study author Donald ORourke, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, USA, told the press: This is an early stage trial, but we are encouraged by the fact that the cells got into the brain, proliferated, and reduced the level of antigen with very little toxicity to the patients. We can build on this as a therapeutic option for these patients. It gives us clues on what to do next.

By Shreeya Nanda

medwireNews is an independent medical news service provided by Springer Healthcare. 2017 Springer Healthcare part of the Springer Nature group

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Mutation-directed CAR T cell therapy feasible in recurrent glioblastoma - medwireNews

In the days after a heart attack, surviving patients and their loved ones can breathe a sigh of relief that the immediate danger is over but the scar tissue that forms during the long healing process can inflict lasting damage. Too often it restricts the hearts ability to fill properly between beats, disrupting rhythm and ultimately leading to heart failure. Yet a new possible treatment may help to revitalize an injured ticker.

A cadre of scientists and companies is now trying to prevent or reverse cardiac damage by infusing a cocktail of stem cells into weakened hearts. One company, Melbourne, Australiabased Mesoblast, is already in late-stage clinical trials, treating hundreds of chronic heart failure patients with stem cell precursors drawn from healthy donors hip bones. A randomized trial that includes a placebo group is scheduled to complete enrollment next year.

Mesoblasts earlier-stage trials, published in 2015 inCirculation Research, found that patients who received injections of its cell mixture had no further problems related to heart failure.

Promising results from the new trial would be a major step forward for a field that has long been criticized for studies that are poorly designed, incomplete or lack control-group comparisons, as well as for the peddling of unproved therapies in many clinics worldwide.

Another company, Belgium-based TiGenix, hopes to attack scar tissue before it forms by treating patients with a mixture of heart stem cells within seven days of a heart attack. This approach has just completed phase II trials, but no findings have yet been published.

There are still many unanswered questions about how stem cells typically derived from bones could help heal the heart. Leading theories suggest they may help fight inflammation, revitalize existing heart cells, or drive those cells to divide or promote new blood-vessel growth, says Richard Lee, leader of the cardiovascular program at the Harvard Stem Cell Institute. Other stem cell scientists, including Joshua Hare, who conducted earlier-stage Mesoblast research and directs the Interdisciplinary Stem Cell Institute at the University of Miami, say the cells may work in multiple ways to heal scar tissue. According to Hare, the stem cells could ultimately be a truly regenerative treatment.

Read more from the original source:
Stem cell therapy for heart failure gets a gold-standard trial - Salon

Researchers have created a method to kill cancerous tissue without causing the harmful side effects of chemotherapy.

Medical researchers at the University of California, Irvine have created a stem cell-based method to zero in on cancerous tissue. This method kills the cancerous tissue without causing the nasty side effects of chemotherapy. Such side effects are avoided by treating the disease in a more localized manner. The advancement was spearheaded by associate professor of pharmaceutical sciences Weian Zhao. The details of the stem cell therapy were recently published in Science Translational Medicine.

About the new Stem Cell Therapy

Zhao's team programmed stem cells derived from human bone marrow to pinpoint the specific properties of cancerous tissue. They implemented a portion of code to these engineered cells to identify stiff cancerous tissue, lock onto it and implement therapeutics. The researchers safely used this new stem cell therapy in mice to kill metastatic breast cancer that had moved to the lungs. They transplanted these engineered stem cells in order for the teamto pinpoint and settle in the site of the tumor.

Once the stem cells reached the tumor, they released enzymes referred to as cytosine deaminase. The mice were then provided with an inactive chemotherapy known as prodrug 5-flurocytosine. The tumor enzymes stimulated the chemotherapy into action. Zhao stated his team zeroed in on metastatic cancer that occurs when the disease moves to additional parts of the body. Metastatic tumors are especially dangerous. They are responsible for90 percent of all cancer deaths.

Why the new Stem Cell Therapy is Important

Zhao is adamant his stem cell therapy represents an important newparadigm in the context of cancer therapy. Indeed, Zhao has blazed a trail in a new direction that others will likely follow in the years to come. It is possible his new stem cell therapy serves as an alternative and more effective means of treating cancer. This stem cell therapy will serve as an alternative to numerous forms of chemotherapy that typically have nasty side effects. Chemotherapy certainly kills plenty of growing cancer cells yet it can also harm healthy cells. The new type of treatment keys in on metastatic tissue that allows for the avoidance of the undesirable side effects produced by chemotherapy.

Though the published piece describing this stem cell therapy is centered on breast cancer metastases within thelungs, the method will soon be applicable to additional metastases. This is due to the fact that numerous solid tumors are stiffer than regular tissue. The new system does not force scientists to invest time and effort to pinpoint and create a brand new protein or genetic marker for each kind of cancer.

The Next Step

At this point in time, Zhao's team has performed pre-clinical animal studies to show the treatment is effective and safe. They plan to segue to human studies in the coming months and years. Zhao's team is currently expanding to additional types of cells such as cancer tissue-sensing and engineered immune system CAR-T (T cells) to treat metastasizing colon and breast cancers. Their goal is totransform this technology for the treatment of additional diseases ranging from diabetes to fibrosis and beyond.

More:
Stem Cell Therapy Selectively Targets and Kills Cancerous Tissue - Anti Aging News

Promising research towards a possible stem cell treatment for several lung conditions has been developed by scientists from the UNC School of Medicine and North Carolina State University. The conditions include idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), and cystic fibrosis often-fatal conditions that affect tens of millions of Americans.

The team of scientists showed that they could harvest lung stem cells from people using a relatively non-invasive, doctors-office technique. They were then able to multiply the harvested lung cells in the lab to yield enough cells sufficient for human therapy.

In a second study, the team demonstrated that in rodents they could use the same type of lung cell to successfully treat a model of IPF a chronic, irreversible, and ultimately fatal disease characterized by a progressive decline in lung function. The researchers have been in discussions with the FDA and are preparing an application for an initial clinical trial in patients with idiopathic pulmonary fibrosis.

Co-senior author of both papers Jason Lobo, MD, an assistant professor of medicine at UNC and medical director of lung transplant and interstitial lung disease, said:

This is the first time anyone has generated potentially therapeutic lung stem cells from minimally invasive biopsy specimens.

Co-senior author Ke Cheng, PhD, an associate professor in NCSUs Department of Molecular Biomedical Sciences and the UNC/NCSU Joint Department of Biomedical Engineering, added,

We think the properties of these cells make them potentially therapeutic for a wide range of lung fibrosis diseases.

These diseases of the lung involve the buildup of fibrous, scar-like tissue, typically due to chronic lung inflammation. As this fibrous tissue replaces working lung tissue, the lungs become less able to transfer oxygen to the blood.

Patients ultimately are at risk of early death from respiratory failure. In the case of IPF, which has been linked to smoking, most patients live for fewer than five years after diagnosis.

The two FDA-approved drug treatments for IPF reduce symptoms but do not stop the underlying disease process. The only effective treatment is a lung transplant, which carries a high mortality risk and involves the long-term use of immunosuppressive drugs.

Scientists have been studying the alternative possibility of using stem cells to treat IPF and other lung fibrosis diseases.

Stem cells are immature cells that can proliferate and turn into adult cells in order to, for example, repair injuries. Some types of stem cells have anti-inflammatory and anti-fibrosis properties that make them particularly attractive as potential treatments for fibrosis diseases.

Cheng and Lobo have focused on a set of stem cells and support cells that reside in the lungs and can be reliably cultured from biopsied lung tissue. The cells are called lung spheroid cells for the distinctive sphere-like structures they form in culture.

As the scientists reported in an initial paper in 2015, lung spheroid cells showed powerful regenerative properties when applied to a mouse model of lung fibrosis. In their therapeutic activity, these cells also outperformed other non-lung-derived stem cells known as mesenchymal stem cells, which are also under investigation to treat fibrosis.

In the first of the two new studies, Lobo and his team showed that they could obtain lung spheroid cells from human lung disease patients with a relatively non-invasive procedure called a transbronchial biopsy.

We snip tiny, seed-sized samples of airway tissue using a bronchoscope, Lobo said. This method involves far less risk to the patient than does a standard, chest-penetrating surgical biopsy of lung tissue.

Cheng and his colleagues cultured lung spheroid cells from these tiny tissue samples until they were numerous enough in the tens of millions to be delivered therapeutically. When they infused the cells intravenously into mice, they found that most of the cells gathered in the animals lungs.

These cells are from the lung, and so in a sense theyre happiest, so to speak, living and working in the lung, Cheng said.

In the second study, published in Stem Cell Translational Medicine, the researchers first induced a lung fibrosis condition in rats.

The condition closely resembled human IPF. Then the researchers injected the new cultured spheroid cells into one group of rats.

Upon studying this group of animals and another group treated with a placebo, the researchers saw healthier overall lung cells and significantly less lung inflammation and fibrosis in the rats treated with lung spheroid cells.

Also, the treatment was safe and effective whether the lung spheroid cells were derived from the recipients own lungs or from the lungs of an unrelated strain of rats, Lobo said. In other words, even if the donated stem cells were foreign, they did not provoke a harmful immune reaction in the recipient animals, as transplanted tissue normally does.

Lobo and Chen expect that when used therapeutically in humans, lung spheroid cells initially would be derived from the patient to minimize any immune-rejection risk.

Ultimately, however, to obtain enough cells for widespread clinical use, doctors might harvest them from healthy volunteers, as well as from whole lungs obtained from organ donation networks. The stem cells could later be used in patients as-is or matched immunologically to recipients in much the same way transplanted organs are typically matched.

Our vision is that we will eventually set up a universal cell donor bank, Cheng said.

Cheng, Lobo, and their teams are now planning an initial study of therapeutic lung spheroid cells in a small group of IPF patients and expect to apply later this year for FDA approval of the study.

In the long run, the scientists hope their lung stem cell therapy will also help patients with other lung fibrosis conditions of which there are dozens, including COPD, cystic fibrosis, and fibro-cavernous pulmonary tuberculosis.

Image: NC State / UNC

More here:
Stem Cell Therapy For Lung Fibrosis Conditions - ReliaWire

The excitement at Jerusalem-based Gamida Cell, a maker of cell and immune therapy technologies, is palpable.

The biotechnology company has started enrolling patients for a last-stage clinical trial for a drug it believes will help increase the success of bone marrow transplants in blood cancer patients, and help them better withstand the ordeal of the lifesaving procedure.

The patients are being enrolled in the US, Spain, The Netherlands and Singapore. Should the results of the trial, as hoped, be positive, that would lead to the launch of a commercially available product in 2020, Gamida Cells CEO Yael Margolin said in an interview with The Times of Israel.

We are at an exciting transition point, and moving from being a research and development firm, based in Israel, to an international commercial firm, said Margolin who has headed the company for the past 12 years in her sun-drenched office at the biotech firms headquarters in Jerusalem. We need to prepare to commercialize the product. We are now looking at various sites in Israel for a new manufacturing facility and looking to employ some 100 people. These workers will be added to the 40 already employed in Jerusalem.

Gamida Cells CEO, Dr. Yael Margolin (Courtesy)

Preliminary clinical data has already revealed that the risk of their leading product for blood cancers, NiCord, not meeting its targets in the Phase 3 trial, is low, added Margolin.

The drug has already received a breakthrough therapy designation by the US Food and Drug Administration (FDA). The designation is given to a drug that is meant to treat a serious or life-threatening condition, and where preliminary clinical evidence indicates that it may demonstrate a substantial improvement on at least one clinically significant target (endpoint) over other available therapies. The designation also entitles the company to get more and closer FDA guidance to help bring the treatment faster to patients.

The combination of the low clinical risk based on the previous trial results and the lower regulatory risk, because the drug is being developed in close collaboration with the FDA, has spurred the company into a flurry of activity that is aimed at scaling up its production facilities to get ready for the day NiCord hits the markets.

The company said last month it raised $40 million from investors including Novartis, which is already a major shareholder in the firm. The funds will support the ongoing Phase 3 stage for NiCord. The company also announced, on July 20, that it received a $3.5-million grant from the Israeli government that will support the further development of NiCord and other drugs that the company is developing, including therapies for sickle cell disease and for blood and solid cancers. Gamida has also appointed a new chief medical officer, Ronit Simantov, who will be based in the US.

The first market for our drug will be the US, Margolin said.

The Gamida Cell lab in Jerusalem where umbilical cord blood is stored in tanks, July 16, 2017. (Shoshanna Solomon/Times of Israel)

NiCord, which would be the first drug developed by Gamida to hit the market if the trial goes well is believed to increase the chances of a successful bone marrow transplantation process for patients who do not have a rapidly available, fully matched, bone marrow donor.

Today some high-risk blood cancers cannot be cured unless patients undergo a bone marrow graft. For that purpose, a perfect 100-percent match needs to be found, a process that in the US takes an average of three to four months, if the patient is lucky. Sometimes, no match is found.

There are 70,000 patients a year globally with blood cancers who need a bone marrow transplant, Margolin said. It is a rare condition. But for that transplant, you need a donor with full tissue matching. As many as 50% dont get to the transplant phase, because they havent found a matching donor in time.

Umbilical cord blood collected from newborn babies contains stem cells, which can be used to treat diseases. Today cord-blood banks around the world store the cord blood. It great advantage is that because it is so young, there is no need for a full tissue matching.

The big advantage with umbilical blood is that you dont need full tissue matching; a partial match is enough, Margolin continued. Most patients generally find at least one unit of cord blood that partially matches them.

Stem cells in a bag in Gamida Cells Jerusalem lab, July 16, 2017 (Shoshanna Solomon/Times of Israel)

The problem is that the quantity of cells in each unit is not huge, and it is the number of stem cells in the cord blood that is critical to the success of transplantation.

Our idea is to leverage the advantages of the cord blood and overcome the limitations of the cell number by applying our own platform technology, called NAM Technology, added Margolin. This technology allows us to take one unit of umbilical cord blood and expand the number of stem cells within it and enhance their performance.

Gamida Cell selects the stem cells from the unit and puts them in a culture together with a molecule called Nicotinamide (NAM) a form of Vitamin B3 and adds other ingredients. This culture, to which the firm holds intellectual property rights, increases the number of stem cells, and enhances their functionality, Margolin said.

The cells are then harvested from the culture, frozen in a small blood-bag in a final formulation that is ready for infusion, and then shipped to hospitals via couriers. Doctors thaw the product by the bedside of the patients and infuse the fluid into them.

From start to finish, our process takes three weeks, Margolin said. The average search for a bone marrow match takes three to four months.

The clinical trial underway is enrolling patients aged 16 years and older.

An earlier trial of the drug showed that patients transplanted with NiCord showed a more rapid engraftment the amount of time needed for the development of a minimal amount of white blood cells, or neutrophils, in the blood. That minimum amount indicates the patient is now less vulnerable to infections and bleeding following the transplant, and is an indication of success.

In the pilot phase clinical trials, the median time to neutrophil engraftment with NiCord was 11 days, compared to three to four weeks in patients who received standard umbilical cord blood. The results in a study conducted at Duke University also showed a lower rate of infection 22% vs 54%; and a lower duration of hospitalization compared to standard umbilical cord engraftment, Margolin said.

Now the company is enrolling patients for its larger, Phase 3 multi-national, randomized controlled registration study. And in February it said it had already transplanted its first patient, as part of the trial.

We hope to publish positive topline data from the Phase3 study in the first half of 2019 and launch the product on the market in 2020, she said.

Metal barrel with a frozen bag of umbilical cord stem cells ready for delivery from Gamida Cells Jerusalem lab, July 16, 2017. (Shoshanna Solomon/Times of Israel)

A metal barrel within which was a frozen bag of umbilical cord stem cells was waiting to be picked by a courier in the lobby of the Gamida Cell offices, ready to be thawed and injected into a patient somewhere around the world.

We have a sophisticated infrastructure that coordinates everything between the cord bank blood and our manufacturing site and the hospital where the patient is to be treated, Margolin continued. This infrastructure is 100% robust, but we plan to scale this up toward commercialization.

The $40 million in funds the company raised last month is expected to last until late 2019. After that, she added, all options are on the table: an IPO, or teaming up with a strategic partner, are both possibilities for the future.

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Cell therapy firm in flurry of activity as hope nears for bone marrow ... - The Times of Israel