Stem Cell Clinic

Is it time to start worrying about conscious human mini-brains? – PLoS Blogs (blog)

By Induced Pluripotent Stem Cells

A human iPSC cerebral organoid in which pigmented retinal epithelial cells can be seen (from the work of McClure-Begley, Mike Klymkowsky, and William Old.)

The fact that experiments on people are severely constrained is a major obstacle in understanding human development and disease. Some of these constraints are moral and ethical and clearly appropriate and necessary given the depressing history of medical atrocities. Others are technical, associated with the slow pace of human development. The combination of moral and technical factors has driven experimental biologists to explore the behavior of a wide range of model systems from bacteria, yeasts, fruit flies, and worms to fish, frogs, birds, rodents, and primates. Justified by the deep evolutionary continuity between these organisms (after all, all organisms appear to be descended from a single common ancestor and share many molecular features), experimental evolution-based studies of model systems have led to many therapeutically valuable insights in humans something that I suspect a devotee of intelligent design creationism would be hard pressed to predict or explain (post link).

While humans are closely related to other mammals, it is immediately obvious that there are important differences after all people are instantly recognizable from members of other closely related species and certainly look and behave differently from mice. For example, the surface layer of our brains are extensively folded (they are known as gyrencephalic) while the brain of a mouse is smooth as a babys bottom (and referred to as lissencephalic). In humans, the failure of the brain cortex to fold is known as lissencephaly, a disorder associated with several severe neurological defects. With the advent of more and more genomic sequence data, we can identify human specific molecular (genomic) differences. Many of these sequence differences occur in regions of our DNA that regulate when and where specific genes are expressed. Sholtis & Noonan (1) provide an example: the HACNS1 locus is a 81 basepair region that is highly conserved in various vertebrates from birds to chimpanzees; there are 13 human specific changes in this sequence that appear to alter its activity, leading to human-specific changes in the expression of nearby genes (). At this point ~1000 genetic elements that are different in humans compared to other vertebrates have been identified and more are likely to emerge (2). Such human-specific changes can make modeling human-specific behaviors, at the cellular, tissue, organ, and organism level, in non-human model systems difficult and problematic (3,4). It is for this reason that scientists have attempted to generate better human specific systems.

One particularly promising approach is based on what are known as embryonic stem cells (ESCs) or pluripotent stem cells (PSCs). Human embryonic stem cells are generated from the inner cell mass of a human embryo and so involve the destruction of that embryo which raises a number of ethical and religious concerns as to when life begins (5)(more on that in a future post). Human pluripotent stem cells are isolated from adult tissues but in most cases require invasive harvesting methods that limit their usefulness. Both ESCs and PSCs can be grown in the laboratory and can be induced to differentiate into what are known as gastruloids. Such gastruloids can develop anterior-posterior (head-tail), dorsal-ventral (back-belly), and left-right axes analogous to those found in embryos (6) and adults (top panel). In the case of PSCs, the gastruloid (bottom panel ) is essentially a twin of the organism from which the PSCs were derived, a situation that raises difficult questions: is it a distinct individual, is it the property of the donor or the creation of a technician. The situation will be further complicated if (or rather, when) it becomes possible to generate viable embryos from such gastruloids.

The Nobel prize winning work of Kazutoshi Takahashi and Shinya Yamanaka (7), who devised methods to take differentiated (somatic) human cells and reprogram them into ESC/PSC-like cells, cells known as induced pluripotent stem cells (iPSCs)(8), represented a technical breakthrough that jump-started this field. While the original methods derived sample cells from tissue biopsies, it is possible to reprogramkidney epithelial cells recovered from urine, a non-invasive approach (9,10). Subsequently, Madeline Lancaster, Jurgen Knblich, and colleagues devised an approach by which such cells could be induced to form what they termed cerebral organoids; they used thismethod to examine the developmental defects associated with microencephaly (11). The value of the approach was rapidly recognized and a number of studies on human conditions, including lissencephaly (12), Zika-virus infection-induced microencephaly(13), and Downs syndrome (14); investigatorshave begun to exploit these methodsto study a range of human diseases.

The production of cerebral organoids from reprogrammed human somatic cells has also attracted the attention of the media (15). While mini-brain is certainly a catchier name, it is a less accurate description of a cerebral organoid, itself possibly a bit of an overstatement, since it is not clear exactly how cerebral such organoids are. For example, the developing brain is patterned by embryonic signals that establish its asymmetries; it forms at the anterior end of the neural tube (the nascent central nervous system and spinal cord) and with distinctive anterior-posterior, dorsal-ventral, and left-right asymmetries, something that simple cerebral organoids do not display. Moreover, current methods for generating cerebral organoids involve primarily what are known as neuroectodermal cells our nervous system (and that of other vertebrates) is a specialized form of the embryos surface layer that gets internalized during development. In the embryo, the developing neuroectoderm interacts with cells of the circulatory system (capillaries, veins, and arteries), formed by endothelial cells and what are known as pericytes that surround them. These cells, together with interactions with glial cells (astrocytes, a non-neuronal cell type) combine to form the blood brain barrier. Other glial cells (oligodendrocytes) are also present; in contrast, both types of glia (astrocytes and oligodendrocytes) are rare in the current generation of cerebral organoids. Finally, there are microglial cells, immune system cells that originate from outside the neuroectoderm; they invade and interact with neurons and glia as part of the brains dynamic neural system. The left panel of the figure shows, in highly schematic form how these cells interact (16). The right panel is a drawing of neural tissue stained by the Golgi method (17), which reveals~3-5% of the neurons present. There are at least as many glial cells present, as well as microglia, none of which are visible in the image. At this point, cerebral organoids typically contain few astrocytes and oligodendrocytes, no vasculature, and no microglia. Moreover, they grow to be about 1 to 3 mm in diameter over the course of 6 to 9 months; that is significantly smaller in volume than a fetal or newborns brain. While cerebral organoids can generate structures characteristic of retinal pigment epithelia (top figure) and photo-responsive neurons (18), such as those associated with the retina, an extension of the brain, it is not at all clear that there is any significant sensory input into the neuronal networks that are formed within a cerebral organoid, or any significant outputs, at least compared to the role that the human brain plays in controlling bodily and mental functions.

The reasonable question, then, must be whether a cerebral organoid, which is a relatively simple system of cells (although itself complex), is conscious. It becomes more reasonable as increasingly complex systems are developed, and such work is proceeding apace. Already researchers are manipulating the developing organoids environment to facilitate axis formation, and one can anticipate the introduction of vasculature. Indeed, the generation of microglia-like cells from iPSCs has been reported; such cells can be incorporated into cerebral organoids where they appear to respond to neuronal damage in much the same way as microglia behave in intact neural tissue (19).

We can ask ourselves, what would convince us that a cerebral organoid, living within a laboratory incubator, was conscious? How would such consciousnessmanifest itself? Through some specific pattern of neural activity, perhaps? As a biologist, albeit one primarily interested in molecular and cellular systems, I discount the idea, proposed by some physicists and philosophers as well as the more mystical, that consciousness is a universal property of matter (20,21). I take consciousness to be an emergent property of complex neural systems, generated by evolutionary mechanisms, builtduring embryonic and subsequent development, and influenced bysocial interactions (BLOG LINK) using information encoded within the human genome (something similar to this: A New Theory Explains How Consciousness Evolved). While a future concern, in a world full of more immediate and pressing issues, it will be interesting to listen to the academic, social, and political debate on what to do with mini-brains as they grow in complexity and perhaps inevitably, towards consciousness.

Footnotes and references

Thanks to Rebecca Klymkowsky, Esq. and Joshua Sanes, Ph.D. for editing anddisciplinarysupport.

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Is it time to start worrying about conscious human mini-brains? - PLoS Blogs (blog)

Stem Cells Offer New Solutions for Lung Disease – Miami’s Community Newspapers

By Adult Stem Cells

Kristin Comella, Chief Science Officer

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and is projected to be the third by 2020. COPD is associated with an exaggerated chronic inflammatory response causing airway abnormalities. Patients typically undergo a progression of declining lung function, characterized by an increase of cough, shortness of breath, and mucus production. Extra-pulmonary manifestations of COPD include osteoporosis, cardiovascular disease, skeletal muscle abnormalities, and depression. There is currently no cure and the manifestations can only be treated symptomatically. It afflicts more than 5% of the population in many countries and accounts for more than 600 billion in health care costs, morbidity, and mortality.

Adult stem cells are found in every part of the body and their primary role is to heal and maintain the tissue in which they reside. Stem cells are unspecialized cells capable of renewing themselves by cell division. In addition, they have the ability to differentiate into specialized cell types. Adult stem cells can be harvested from a patients own tissue, such as adipose (fat) tissue, muscle, teeth, skin or bone marrow. One of the most plentiful sources of stem cells in the body is the fat tissue. In fact, approximately 500 times more stem cells can be obtained from fat than bone marrow. Stem cells derived from a patients own fat are referred to as adipose-derived stem cells (ADSCs). Adipose derived stem cells have been explored with respect to their activity in diseases involving significant inflammatory or degenerative components. More recently, adult stem cells have been identified as having the potential to reverse the effects of diseases like COPD.

The mixed population of cells that can be obtained from fat is called a stromal vascular fraction (SVF). The SVF can easily be isolated from fat tissue in approximately 30-90 minutes in a clinic setting (under local anesthesia) using a mini-lipoaspirate technique. The SVF contains all cellular elements of fat, excluding adipocytes. Tens to hundreds of millions of ADSCs can be obtained in the context of the SVF acquired from 20-200 ml of adipose tissue during this out-patient procedure. This sets the stage for their practical use at the point-of-care, in which a preparation of ASC can be provided for infusion or injection after the mini-liposuction. COPD patients who have undergone stem cell therapies often express the willingness to receive additional cell infusions if possible, due to a feeling of well-being associated with the injection. There is early evidence of feasibility and safety of infusions into the patients with COPD. In relevant studies, intravenous infusion of cultured adipose stem cells has been demonstrated to remarkably improve the onset and progression of smoke exposure-induced emphysema in rodents.

Stem cells possess enormous regenerative potential. The potential applications are virtually limitless. Patients can receive cutting edge treatments that are safe, compliant, and effective. Our team has successfully treated over 7000 patients with very few safety concerns reported. One day, stem cell treatments will be the gold standard of care for the treatment of most degenerative diseases. We are extremely encouraged by the positive patient results we are seeing from our physician-based treatments. Our hope is that stem cell therapy will provide relief and an improved quality of life for many patients. The future of medicine is here!

For additional information on Stem Cell Centers of Excellences South Miami clinic, visit http://www.stemcellcoe.com.

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Stem Cells Offer New Solutions for Lung Disease - Miami's Community Newspapers

Revolutionary Israeli ALS Therapy Receives FDA Approval for Phase 3 Clinical Trials – TheTower.org

By Stem Cell Medical Center

BrainStorm Cell Therapeuticsof Petah Tikva is recruiting American patients for a Phase 3 clinical study of itsNurOwn stem-cell treatmentintended to halt progression of amyotrophic lateral sclerosis (ALS).

The announcement was made in a patient webinar last week.

The NurOwn platform grew out of a technique developed at Tel Aviv University for growing and enhancing stem cells harvested from patients own bone marrow. The enhanced cells, injected via lumbar puncture, secrete elevated levels of nerve-growth factors believed to protect existing motor neurons, promote motor neuron growth and reestablish nerve-muscle interaction.

A 24-week Phase 2 safety study was concluded in 2016 on 48 participants (36 treated, 12 placebo) with possible, probable and definite ALS. This study was done at the University of Massachusetts Medical School, Massachusetts General Hospital and the Mayo Clinic.

The Phase 3 double-blind, placebo-controlled study, to begin enrollment in August, will look at efficacy and safety of repeated doses. The California Institute for Regenerative Medicine has awarded Brainstorm a $16 million grant to support the pivotal trial.

This study will accept 200 randomized study participants between the ages of 18 and 60 (half getting the treatment and half a placebo) at the three previous centers as well as California Pacific Medical Center in San Francisco, UC-Irvine near Los Angeles and another site not announced.

Potential participants must live within about 100 miles of one of the centers for ease of follow-up. They will receive three doses over a 16-week treatment phase and then undergo 28 weeks of follow-up.

BrainStorm President and CEO Chaim Lebovits said he hopes to get approval by the end of the year for a hospital exemption program in Israel an accelerated regulatory pathway that would clear the way for a first batch of 50 patients to receive NurOwn at Tel Aviv Sourasky Medical Center. However, there will be no compassionate treatment using NurOwn in Israel or elsewhere.

The NurOwn platform technology also has potential applications in any neurodegenerative disease, such as multiple sclerosis and Parkinsons.

(via Israel21c)

[Photo:TheMarker Online / YouTube]

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Revolutionary Israeli ALS Therapy Receives FDA Approval for Phase 3 Clinical Trials - TheTower.org

Cells that stand in the way of HIV cure: Discovery expands understanding of marrow’s role – Medical Xpress

By Stem Cell Medical Center

July 31, 2017 Illustration incorporating gene-expression maps and cell images from the new research. Credit: University of Michigan

Every day, 17 million HIV-infected people around the world swallow pills that keep the virus inside them at bay.

That is, as long as they swallow those pills every day for the rest of their life.

But no matter how many drugs they take, they'll always have the virus in them, lurking in their white blood cells like a fugitive from justice.

And if they ever stop, HIV will come out of hiding and bring down their immune system from the inside out, causing the disease known as AIDS and potentially spreading to others before killing them.

Now, new research into HIV's hiding places reveals new clues about exactly how it persists in the body for years. The discovery could speed the search for drugs that can flush HIV out of its long-term hideouts and cure an infection for good.

In a new paper in PLoS Pathogens, a team led by University of Michigan researcher Kathleen Collins, M.D., Ph.D. reports that HIV hides in more types of bone marrow cells than previously thought - and that when these cells divide, they can pass the virus's genetic material down to their "daughter" cells intact.

This keeps the infection going for years, without tipping off the armed guards of the immune system.

Collins and her colleagues made the discovery in bone marrow samples donated by dozens of long-term HIV patients treated at U-M's academic medical center, Michigan Medicine, and at Henry Ford Health System in Detroit.

Using funding from the National Institutes of Health, they found that HIV can hide in hematopoietic progenitor cells (HPCs), which also serve as the parents of new blood cells that replace worn-out ones on a regular basis. HIV tricks the cells into incorporating the virus's genetic material into the cells' own DNA.

"Looking for the cells that harbor functional HIV is like searching for a needle in a haystack. Our new results expand our understanding of the type of cells that can do it," says Collins, a professor of Microbiology and Immunology and of Infectious Disease at the U-M Medical School. "It's like a cancer biology problem, only the 'mutation' in the cells is the inserted viral genome."

HPCs are made by hematopoietic stem cells, the "master cells" of blood production found in the marrow. Previous research had shown that HIV can hide for years in the bone marrow.

But it was not known whether the virus persisted only in stem cells or whether the reservoir could include more differentiated progenitor cells. Demonstrating that progenitor cells form a long-lived reservoir of virus expands the number of cell types that need to be targeted.

By demonstrating that HIV genetic material can lurk in blood progenitor cells, the researchers extend other recent studies indicating that such cells can live for years, says Collins, whose lab team included lead author Nadia Sebastian, a U-M M.D./Ph.D. student.

She notes that from the point of view of the virus, finding a harbor in this kind of cell means it can hedge its bets, giving it a chance at survival and eventual reproduction if its host's defenses weaken. The virus that causes chicken pox - varicella - also does this, hiding out in nerve cells just under the skin for years until it awakens and causes the painful condition called shingles.

Knowing exactly what cells harbor HIV over the long-term is crucial to battling persistent infections. Other research has focused on the T cells that carry out key immune system functions.

"Having established this, now we're poised to ask if we can treat HIV infection by targeting hematopoietic progenitor cells," she explains. The team is evaluating potential drugs that could kill just these cells.

The research team on the new paper also includes former U-M stem cell researcher Sean Morrison, Ph.D., who now leads a research center at the University of Texas Southwestern Medical Center. Morrison's lab uses mice as a model to study stem and progenitor cells.

They find in the new paper that in order for HIV to infect a progenitor cell, that cell must have a type of receptor on its surface, called CD4, that the virus can attach to. Additionally, the researchers show that two subtypes of HIV can infect these cells: those that use the CXCR4 co-receptor to enter cells as well as those that use CCR5, which expands the types of HIVs that can potentially cause reservoirs.

Finding those progenitor cells in the marrow of the human patients who agreed to undergo a biopsy for the sake of pure research was tricky, Collins says. But thanks to them, researchers are a step closer to a day when HIV infection is no longer a life sentence for millions of people around the world.

"Moving from the state we're in, where patients will always have to be on these drugs, to a better form of therapy where they can stop, would have a huge effect," she says. "Today's medications have side effects, as well as financial costs. To get to the next step, we need to target the types of cells that form a latent infection, including these progenitor cells."

Explore further: Scientists find that persistent infections in mice exhaust progenitors of all blood cells

More information: Nadia T. Sebastian et al, CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo, PLOS Pathogens (2017). DOI: 10.1371/journal.ppat.1006509

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More than 60 US clinics have sold unproven stem cell therapies for heart failure – New York Post

By Stem Cell Medical Center

Stem cell therapy isnt approved to treat heart failure in the US, but dozens of clinics nationwide advertise the treatments anyway, often charging thousands of dollars for procedures that may not be safe or effective, a new study suggests.

Researchers found 61 centers offering stem cell therapies for heart failure as of last year in the US alone, including five that claimed to have performed more than 100 procedures. Only nine centers required copies of patients medical records and just one facility said it had a board certified cardiologist on staff.

We simply do not know anything about the quality of the treatment delivered at these centers, said senior study author Dr. Paul Hauptman director of heart failure at Saint Louis University Hospital.

These centers are not regulated in any way, Hauptman said by email.

Almost 6 million Americans have heart failure, and its one of the most common reasons older adults go to the hospital, according to the American Heart Association.

It happens when the heart muscle is too weak to effectively pump enough blood through the body. Symptoms can include fatigue, weight gain from fluid retention, shortness of breath and coughing or wheezing. Medications can help strengthen the heart and minimize fluid buildup in the body.

While some experimental stem cell therapies for heart failure are currently being tested in late-stage human trials, none have won approval from the US Food and Drug Administration.

In theory, after a transplant, stem cells could permanently become part of the diseased heart and either help grow new healthy heart tissue or tell existing cells to work better, said Paul Knoepfler, a cell biology researcher at the University of California Davis School of Medicine in Sacramento who wasnt involved in the study.

Its also possible stem cells could temporarily visit the heart and stimulate a positive response in cells already there, he said.

Even though theres no conclusive proof yet that any stem cell treatments are safe and effective for heart failure, centers contacted for the study charge an average of $7,694 for each treatment using patients own stem cells and $6,038 for each procedure with donor stem cells.

In one instance, though, a clinic staff member said, If you have a million dollars to spend we will set you up with weekly infusions.

Hauptmans team had used a standard script when contacting each center, asking about the stem cell treatment itself, medical exams before and afterward and pricing.

Among the other responses they received from clinic staff were remarks such as, If you know anyone that can start an IV, a neighbor that is a nurse for example, we can send you the stem cells and that person can administer them to you and We hope you dont believe your doctor when they tell you there is nothing they can do, you were smart to call us.

None of the sites in the study discussed what methods they used to isolate or identify stem cells, though most claimed to use patients cells and 24 said they got cells from fat tissue.

Most centers claimed to deliver cells intravenously, researchers report in JAMA Internal Medicine.

This approach has been associated with complications such as stroke, in which infused cells block blood vessels in the brain, said Douglas Sipp, a researcher at RIKEN Center for Developmental Biology in Kobe, Japan, who wasnt involved in the study.

The biggest risk is that patients will waste their money, time and hopes on an unnecessary and useless invasive procedure, Sipp said by email.

If any stem cell treatment did ultimately prove safe and effective enough to win FDA approval, it would likely offer a significant improvement over the limited treatment options currently available, said Leigh Turner, a researcher at the University of Minnesota Center for Bioethics who wasnt involved in the study.

But its impossible to say what patients would get at unregulated clinics offering unapproved stem cell therapies, Turner said by email. In at least two cases unrelated to the current study, patients died after getting stem cell procedures at a clinic in Florida, and in another case at a different Florida clinic, a woman went blind, Turner noted.

Clinics marketing stem cell treatments to patients suffering from heart failure might be administering anything from slurries of mixed cells, some of which might be stem cells, to nothing more than cellular debris, Turner said. Often one can only speculate.

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More than 60 US clinics have sold unproven stem cell therapies for heart failure - New York Post

Hypothalamic Stem Cells Could Provide New Insights Into Aging – Futurism

By Stell Cell Research

Hypothalamic Stem Cells

The hypothalamus is the region of the brain that helps to regulate internal conditions like body temperature and blood concentration, but new research shows that it may fail us as we age. The research indicates that as the hypothalamuss stem cells die off, the region actually starts to promote aging, causing mental and physical faculties to decline at a more rapid pace.

In the past, researchers have observed that the hypothalamus becomes inflamed over time. This lead them to posit that the area is connected to aging. Recent research on mice proved that reversing the inflammation in the hypothalamus increases the animals life span and slows physical deterioration. In this latest study, scientists focusedon the stem cells of the hypothalamus. In younger animals, these stem cells divide and replace damaged and dead cells. However, as this research shows, over time the number of stem cells present in the hypothalamus drops. Inold age, they are essentially gone.

The team believed they were on to something, but undertook some practical experiments to see if their ideas were borne out by the evidence. First, they altered mice genetically to ensure theyd be out of stem cells(at a point earlier than would occur naturally). Reducing the stem cells in the mice by around 70 percent meant a life span that was about 8 percent shorter. This accelerated loss of stem cells also caused a loss of coordination, endurance, and memory, as well as behavior that was less youthful, curious, and social. When the team injected stem cells into the hypothalami of middle-aged mice, those mice gained about about 10 percent more mental and physical capabilities compared to mice injected with regular brain cells.

Originally, scientists believed that the stem cell loss could besignificant because it meant the host was unable to repair and replace damaged and dead cells. However, when the hypothalami of middle-aged mice were injected with stem cells, they improved too rapidly for this to be thecorrect mechanism. Instead, the team suspected microRNAs might be at work.

The RNA molecules, called microRNAs, are manufactured and released by stem cells to carry messages to other cells. Practically, based on the messages they carry, microRNAs mayalter the proteins cells produce. The researchers discovered that the stem cells in the hypothalamus produce massive amounts of microRNAs contained in tiny exosomes. In fact, when they injected mice with exosomes packed with microRNA from young hypothalamus stem cells, the effects were almost as effective in slowing signs of mental and physical aging as injections of stem cells were.

Recent research has focused on the role of mitochondria in aging and on the use of induced pluripotent stem (iPS) cells in combatting aging in hematopoietic stem cells. Research from this year has also shown that cannabis-based treatment appears to reverse aging in the brains of mice. Concerning thisresearch, protecting or replacing the stem cells of the hypothalamus or somehow reinforcing or replacing the microRNA effects could slow aging in humans. This could mean testing current drugs such as acarbose (presently used to treat diabetes) to see if they can suppress the hypothalamic inflammation that causes the stem cells to die.

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NantKwest Announces Durable Complete Responses in Phase I … – Business Wire (press release)

By Uncategorized

CULVER CITY, Calif.--(BUSINESS WIRE)--NantKwest Inc. (Nasdaq:NK), a pioneering, next-generation, clinical-stage immunotherapy company focused on harnessing the unique power of the immune system using natural killer (NK) cells to treat cancer, infectious diseases, and inflammatory diseases, today announcedthe final results of a phase Iclinical trial of the companys aNK cell therapyplatforminrelapsed hematological malignancies.

The datapublished in thejournalOncotargetbyinvestigatorsat Princess Margaret Cancer Centre in Toronto, Canada,demonstratedcontinuing evidence of safety and efficacy, with an overall response rate of 42% and no evidence of grade 3 or 4 adverse events from the infusions. Of note 2 out of the 12 patients in the safety study with relapsed Hodgkin's Lymphoma and Multiple Myeloma, demonstrated durable complete response with single agent aNK therapy, and remain free of disease to date, 10 years and 2 years respectively.

Our study was designed to assess safety andpreliminary evidence ofefficacy in patients with relapsed, refractory hematological malignancies whose disease recurred afterautologoushematopoieticcell transplantation (AHCT).In this heavilypretreated patient population that hasa particularly poor prognosis, wedemonstrated safetywithminimal toxicityand showed preliminary evidence of efficacy,takingadvantage of the unique properties of natural killer (NK) cells as an immunotherapeuticagent,said Armand Keating, MD, FRCP(C),Director, Cell Therapy Program,Princess Margaret Cancer Centreand University Health Network.

Dr. Keating continued, In this clinical study completed in 2015 of 12 patients with lymphoma and multiple myeloma who had relapsed after AHCT for refractory/relapsed disease, we report encouraging results with four patients (33%) currently alive and two complete responses, one for over two years and the second for over 10 years and conclude that aNK cell therapy warrants further clinical investigation.

Patrick Soon-Shiong, Chairman and CEO of NantKwestcommented, Consistent with previous studies,Dr. Keatingsclinical trial results, reporting a 42% overall response rate, provide additional clinical validation of the unique potentialtodeliverlong-term remissions withlimitedtoxicityusing the companys novelNK cell therapy.OuraNK cell therapy iscurrently in an ongoing PhaseII clinical study in Merkel cell carcinoma andrepresenta critical,foundational component in the companys recently launched NANT Cancer Vaccine clinical trialprogram.

Dr. Soon-Shiong continued, We believe ourproduct portfolio ofnoveloff-the-shelfNK cell therapiesis unique inofferinga more uniform, consistentand optimized product potency with minimaltoxicityand we remainfocused ontranslating these unique advantages to patient careas rapidly as possible.

aNKCell Therapy Platform

NantKwests aNK cell therapy platformis being developed asan allogeneic, off-the-shelf therapy,offering a potent, standardized, uniform and consistent product, further optimized to enhance the key capability of natural killer cells to directly target and kill cancer cells.This novel cell therapy iscurrentlyinan ongoing Phase II clinical trial in Merkel cell carcinomaand is a critical, foundationalcomponent in the companys recently launch NANT Cancer Vaccine clinical trialprogram.

About NANT Cancer Vaccine

The NANT Cancer Vaccine is the first combination immunotherapy protocol to orchestrate the delivery of metronomic low dose radiation and chemotherapy with molecularly informed tumor associated antigen vaccines and natural killer cells, to activate the innate and adaptive immune system and to induce immunogenic cell death. By inducing immunogenic celldeath and protecting as well as enhancing the innate and adaptive immune system, the NANT Cancer Vaccine seeks to attain long-term sustainable remission of multiple tumor types with lower toxicity and higher efficacy than current standards of care.

About NantKwest

NantKwest(Nasdaq:NK) is a pioneering, next generation, clinical-stage immunotherapy company focused on harnessing the unique power of our immune system using natural killer (NK) cells to treat cancer, infectious diseases and inflammatory diseases. NK cells are the bodys first line of defense due to the innate ability of NK cells to rapidly identify and destroy cells under stress, such as cancer or virally-infected cells.

NantKwests unique NK cell-based platform, with the capacity to grow active killer cells as a biological cancer therapy, has been designed to induce cell death against cancer or infected cells by three different modes of action: (1) Direct killing using activated NK cells (aNK) that release toxic granules directly into the cell through cell to cell contact, (2) Antibody-mediated killing usinghaNKs, which are NK cells engineered to incorporate a high affinity receptor that binds to an administered antibody, enhancing the cancer cell killing effect of that antibody, and (3) Targeted activated killing usingtaNKs, which are NK cells engineered to incorporate chimeric antigen receptors (CARs) to target tumor-specific antigens found on the surface of cancer cells.

Our aNK, haNK and taNK platform addresses certain limitations of T cell therapies including the reduction of risk of serious "cytokine storms" reported after T cell therapy. As an off-the-shelf therapy, NantKwest's NK cells do not rely on a patients own often compromised immune system. In Phase 1 clinical trials in patients with late stage cancer, NantKwest's NK cells have been successfully administered as an outpatient infusion therapy without any reported severe side effects, even at doses of 10 billion cells.

By leveraging an integrated and extensive genomics and transcriptomics discovery and development engine, together with a pipeline of multiple, clinical-stage, immuno-oncology programs that include a Phase 2 trial for a rare form of melanoma and the planned initiation of a clinical trial of NK cells targeted to breast cancer, we believe NantKwest is uniquely positioned to be the premier immunotherapy company and transform medicine by delivering living drugs in a bag and bringing novel NK cell-based therapies to routine clinical care. For more information please visitwww.nantkwest.com.

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Gamida Cell Receives $3.5M Grant from Israeli Government to Help Develop CordIn Therapy – Sickle Cell Anemia News

By Uncategorized

The Israeli government has awardedGamida Cella $3.5 million grant to advance the development of clinical trials forCordIn, a therapy totreatsickle cell disease (SCD) and thalassemia.

The money,granted by the Ministry of Economy and Industrys Israel Innovation Authority (IIA), will also support further development and salesof NiCord, a breakthrough product for blood cancers such as leukemia and lymphoma.

The grant follows the recent closing of a $40 million financing round and the Jerusalem-based companysrecent expansion to theUnited States, after appointing Dr. Ronit Simantovas the companys new U.S.-headquartered chief medical officer.

CordIn is Gamidas candidate for the treatment of SCD and thalassemia, as well as bone marrow failure syndromes and genetic metabolic diseases.Itsa variation of NiCord, developed as an alternative to bone marrow transplants to treat patients with blood cancers who cannot find a donor with fully matched tissue. The product comes from expandingcells from the umbilical cord.

A bone marrow transplant is the only established cure for SCD. Due to the difficulties in finding a suitable match, only a few hundred patients canbe treated this way.

Clinical trial data has been encouraging so far, showing successful and swift engraftment as well as the curing of disease symptoms in these hard to-engraft patients.

Particularly, interim results from a Phase 1/2 clinical trial (NCT02504619) appear to suggest that CordIn could effectively overcome the engraftment barriers of umbilical cord blood and has the potential to increase access to curative transplants for SCD.

We are very pleased with the Israeli governments ongoing contributions and support in helping to bring Gamida Cells very important products to market, Gamida President and CEO Yael Margolin said in a press release. The grant provides additional funding for the development and commercialization of NiCord, as well as our additional pipeline programs.

The Phase 1/2 trial, launchedin January 2015, marked the first time that a patient with SCD was transplanted with CordIn. The transplant took place at UCSF Benioff Childrens Hospital in Oakland, California. The trial is still recruiting patients in the United States.

For more information, please contact Iddo Peleg in Israel at +972-2-659-5666 orclinicaltrials@gamida-cell.com.Those interested can also call Jean-Hugues Dalle in France at +33 1 40 03 53 88 or jhugues.dalle@gmail.com.

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Gamida Cell Receives $3.5M Grant from Israeli Government to Help Develop CordIn Therapy - Sickle Cell Anemia News

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

By Stem Cell Treatment

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 patients - The Times of Israel

US Scientists First Ever To Genetically Modify Human Embryos – Chronicle Day

By Embryonic Stem Cells

The United States seems to be in the running when it comes to the experiments with human DNA. However, the subject s still very much covered with a veil of secrets and questions we have no answers to.

It looks like that the MIT Technology Review published a news report last week concerning the experiments in which the aim was to create genetically modified human embryos. This research was led by Shoukhrat Mitalipov, director of the Oregon Health & Science Universitys Center for Embryonic Cell and Gene Therapy, but neither he or his unversity wanted to make any statements concerning the research.

The university press office did, however, release a statement which said: Results of the peer-reviewed study are expected to be published soon in a scientific journal. No further information will be provided before then. It is pretty clear that there will be no way to get the extra details on the research before the study is published in the journal as to avoid any speculation and possible issues.

Mitalipov has also refused to comment any of the questions or statements released, including the report that was published. He has also not confirmed not negated that he has seen the report.

In 2013 Mitalipov and his research team had their first breakthrough when they cloned human stem cells and reprogrammed them to go back to their embryonic state. In 2007, they have announced that they made a clone of monkey embryo and managed to extract the cells from it.

Although it is not certain, and at this time cannot be confirmed, it is suspected that the genes targeted in this particular research are the ones associated with inherited diseases. Arthur Caplan, a professor and founder of the division of bioethics at New York University Langone Medical Center, who was not involved in the research commented: Im not surprised that they were looking at genetic diseases to try and see if they could target them, because thats exactly where I think the future inevitably leads.

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US Scientists First Ever To Genetically Modify Human Embryos - Chronicle Day

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