Category Archives: Stem Cell Medical Center


BioLineRx to Present Two Posters at the Society for Immunotherapy of Cancer (SITC) 2019 – PRNewswire

TEL AVIV, Israel, Oct. 31, 2019 /PRNewswire/ -- BioLineRx Ltd. (NASDAQ: BLRX) (TASE: BLRX), a clinical-stage biopharmaceutical company focused on oncology, announced today that it will deliver the following poster presentations at the Society for Immunotherapy of Cancer(SITC) 34th Annual Meeting to take place November 6-10, 2019 at the Gaylord National Hotel & Convention Center in Baltimore, Maryland:

About BL-8040

BL-8040 is a short synthetic peptide that functions as a high-affinity best-in-class antagonist for CXCR4, a chemokine receptor over-expressed in many human cancers, where it has been shown to be correlated with poor prognosis, and plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance. CXCR4 is also directly involved in the homing and retention of hematopoietic stem cells (HSCs) and various hematological malignant cells in the bone marrow.

In a number of clinical and pre-clinical studies, BL-8040 has shown a critical role in immune cell trafficking, tumor infiltration by immune effector T cells and reduction in immunosuppressive cells within the tumor niche, turning "cold" tumors, such as pancreatic cancer, into "hot" tumors (i.e., sensitizing them to immune check point inhibitors). BL-8040-mediated inhibition of the CXCR4-CXCL12 (SDF-1) axis has also shown robust mobilization of HSCs for transplantation in hematological malignancies.

BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

About BioLineRx

BioLineRx is a clinical-stage biopharmaceutical company focused on multiple oncology indications. The Company'slead program, BL-8040, is a cancer therapy platform currently being evaluated in a Phase 2a study in pancreatic cancer in combination with KEYTRUDA and chemotherapy under a collaboration agreement with MSD. BL-8040 is also being evaluated in a Phase 2b study in consolidation AML and a Phase 3 study in stem cell mobilization for autologous bone-marrow transplantation. In addition, the Company has an ongoing collaboration agreement with Genentech, a member of the Roche Group, evaluating BL-8040 in combination with Genentech's atezolizumab in two Phase 1b/2 solid tumor studies.

BioLineRx is developing a second oncology program, AGI-134, an immunotherapy treatment for multiple solid tumors that is currently being evaluated in a Phase 1/2a study.

For additional information on BioLineRx, please visit the Company's website at http://www.biolinerx.com, where you can review the Company's SEC filings, press releases, announcements and events. BioLineRx industry updates are also regularly updated on Facebook,Twitter, and LinkedIn.

Various statements in this release concerning BioLineRx's future expectations constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include words such as "may," "expects," "anticipates," "believes," and "intends," and describe opinions about future events. These forward-looking statements involve known and unknown risks and uncertainties that may cause the actual results, performance or achievements of BioLineRx to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Some of these risks are: changes in relationships with collaborators; the impact of competitive products and technological changes; risks relating to the development of new products; and the ability to implement technological improvements. These and other factors are more fully discussed in the "Risk Factors" section of BioLineRx's most recent annual report on Form 20-F filed with the Securities and Exchange Commission on March 28, 2019. In addition, any forward-looking statements represent BioLineRx's views only as of the date of this release and should not be relied upon as representing its views as of any subsequent date. BioLineRx does not assume any obligation to update any forward-looking statements unless required by law.

Contact:Tim McCarthyLifeSci Advisors, LLC+1-212-915-2564tim@lifesciadvisors.com

or

Tsipi HaitovskyPublic Relations+972-52-598-9892tsipihai5@gmail.com

SOURCE BioLineRx Ltd.

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BioLineRx to Present Two Posters at the Society for Immunotherapy of Cancer (SITC) 2019 - PRNewswire

Introducing: iPSC Collection from Tauopathy Patients – Alzforum

23 Oct 2019

A multi-institutional group, including members of the Tau Consortium, unveiled a stem cell tool kit for scientists studying primary tauopathies. In the November 12 issue of Stem Cell Reports, researchers co-led by Celeste Karch ofWashington University, St. Louis, and Alison Goate and Sally Temple of Icahn School of Medicine in New York, describe a collection of fibroblasts, induced pluripotent stem cells, and neural precursor cells. The cells come from 140 skin samples, some given by donors with richly documented clinical histories who carry pathogenic MAPT mutations or risk variants. Others come from noncarrier family members, patients with a sporadic tauopathy, and cognitively normal controls. The set includes induced pluripotent stem cell lines from 31 donors and 21 CRISPR-engineered isogenic lines. The cells are available to other researchers for study.

These types of high-quality repositories are becoming increasingly important for the scientific community, Clive Svendsen of the Cedars-Sinai Medical Center in Los Angeles wrote to Alzforum.

This is the way the field is going, agreed Lawrence Golbe of CurePSP, New York. Golbes organization funds research into progressive nuclear palsy (PSP) and related disorders, and collaborates with the Tau Consortium on other projects. Enthusiastic about the resources potential, Golbe hopes CurePSP grantees will get an automatic pass to use the cells.

Choice Mutations. Cells in the new iPSC collection carry some of the most common MAPT mutations, covering a wide range of clinical and neuropathological phenotypes of frontotemporal lobe dementia (FTLD)-Tau. [Courtesy of Karch et al., 2019.]

Tauopathies have proven difficult to study in animal models, in part because unlike other neuropathologies, they seem to afflict only humans (Heuer et al., 2012). Moreover, while adult human brains express approximately equal amounts of the tau spliced isoforms 3R and 4R, rodents produce almost exclusively 4R (Trabzuni et al., 2012). This is problematic. For example, leading proposals to explain how tau mutations cause disease point to abnormalities in splicing and microtubule binding, which differ between isoforms. The models we had been focusing on were not capturing the complexity of MAPT in human cells, said first author Karch. As a result, human induced pluripotent stem cells (iPSCs) have been gaining popularity in the field. The NINDS Human Cell and Data Repository is helping meet the demand by offering iPSC lines derived from 10 patients harboring MAPT mutations.

However, Karch and her collaborators think the field could benefit from a larger and more diverse collection of human cells, including isogenic iPSC lines. To accomplish this, they collected skin samples from 140 people carrying MAPT pathogenic mutations or risk variants, non-mutation carriers, and patients with sporadic PSP or corticobasal syndrome (CBS), most with comprehensive clinical histories. Although a few cells came from the NINDS repository, most came from patients participating in longitudinal studies at the Memory and Aging Center at the University of California, San Francisco, and the Knight Alzheimer Disease Research Center at WashU. The clinical records of most of these patients include detailed neurological and neuropathological workups, as well as fluid biomarkers and neuroimaging data collected from MRI, A-PET, and tau-PET studies.

To capture a broad range of phenotypes associated with some of the most common MAPT mutations, the authors created 36 fibroblast lines and 29 iPSC lines from individuals carrying the P301L, S305I,IVS10+16, V337M, G389R, and R406W mutations, as well as from carriers of the A152T variant, which increases the risk for both PSP and CBS (image above). The latter could be particularly useful for dissecting the mechanisms that underlie the phenotypic differences between the two diseases. The researchers also obtained iPSC lines from two noncarrier family members, and two people who suffered from autopsy-confirmed sporadic PSP. In addition, they stored fibroblast lines from 12 patients with sporadic PSP, five with CBS, 10 with a mixed PSP/CBS presentation, and 69 cognitively normal controls.

Biopsies are available for 27 of the 31 patients whose cells were used to generate iPSCs, and autopsy data for seven, including the two cases of sporadic PSP.

Importantly, the researchers edited 21 iPSC lines using CRISPR/Cas 9. They corrected cells with these mutations: MAPT IVS10+16,P301L, S305I, R406W, and V337M. Conversely, they inserted into control iPSCs these mutations: R5H, P301L,G389R, S305I, or S305S.

The authors also created a stem cell line carrying MAPT P301S,a mutation commonly overexpressed in tauopathy mouse models but not present in the available donors, by editing the P301L line. Isogenic lines are so powerful, particularly in these diseases which are so variable in their onset and progression, even within the same family, said Karch. Gnter Hglinger and Tabea Strauss at the German Center for Neurodegenerative Disease (DZNE) in Munich agreed. Having a pool of cell lines with different disease-linked mutations and risk variants from several individuals and their isogenic control cells is an excellent resource for the research community to enlighten disease mechanisms, they wrote (full comment below).

Several of the reported lines have already starred in recent studies of tauopathy mechanisms and candidate therapies (e.g., Sep 2019 conference news; Nakamura et al., 2019; Hernandez et al., 2019; Silva et al., 2019).

Karch and colleagues have partially differentiated some of the iPSCs and stored them as neural progenitor cells (NPCs), so that researchers can relatively easily thaw, expand, and differentiate them into neurons. These NPCs have proved useful for large-scale functional-genomics studies, proteomics, and genetic modifier screens (e.g., Cheng et al., 2017; Boselli et al., 2017;Tian et al., 2019).

In addition, the authors inserted a neurogenin-2 transgene into two healthy controls and two MAPT mutant stem cells, P301L and R406W. Neurogenin-2 enables low-cost, large-scale differentiation of stem cells into homogenous excitatory neurons. These transgenic cells are particularly useful for high-throughput drug screens (Wang et al., 2017; Sohn et al., 2019).

Researchers can request all the reported cells online at http://neuralsci.org/tau. They must provide a summary of experimental plans, an institutional material transfer agreement, and a nominal fee to cover maintenance and distribution costs. Karch said the process resembles that of the Coriell Institute and the NINDS repository. Our goal is to share with as few hurdles as possible, she said.

While the authors are still reprogramming fibroblasts they have already collected, they also plan to add more causative mutations, generate more isogenic lines, and obtain more cells from members of the same families to help shed light on phenotypic variability. In addition, Karch said, she hopes repository users will resubmit lines with new modifications they generate.

Jeffrey Rothstein, Johns Hopkins University, Baltimore, welcomed the new resource. I think it is great they have assembled this collection, he said. Rothstein founded and co-directs the Answer ALS research project, which has amassed 600 iPSC lines from controls and patients with amyotrophic lateral sclerosis (ALS).

Rothstein suggested the tauopathy collection may want to prioritize adding cells from donors with the most common form of disease, that is, sporadic. His group aims to generate 1,000 iPSC lines, with a large fraction representing sporadic diseasealso the most common form of ALSto identify the most prevalent disease subtypes. One strategy that has helped his group build their collection, he said, is using peripheral blood mononuclear cells instead of fibroblasts to create iPSCs. More donors are willing to donate blood than have a piece of skin punched out. In addition, iPSCs derived from blood cells are genetically more stable, he noted.

Rothstein emphasized the importance of assembling a large collection of healthy controls. Although isogenic controls are of great value, he cautioned they can be subject to artifacts. One problem is that the cell population can change due to selective pressures during CRISPR editing (Budde et al., 2017). To address this, Karch and colleagues are collecting not only modified iPSC clones, but also control clones that have gone through the editing pipeline but remain unmodified.

Stem-cell users studying tauopathies face another challenge: iPSC-derived neurons express primarily the fetal isoform of tau, 3R0N. However, citing a study that shows three-dimensional neuronal cultures switch to the adult profile relatively quickly (Miguel et al., 2019), Hglinger and Strauss wrote, [It] allows us to be optimistic that current challenges of this model system can be overcome in the future.Marina Chicurel

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Introducing: iPSC Collection from Tauopathy Patients - Alzforum

Artificial embryo without sperm or egg forms live fetus – ZME Science

For the very first time, scientists have made artificial embryos from scratch, without sperm or egg, and implanted them into female mice. The embryos developed into live fetuses, but these exhibited major malformations.

The team at the University of Texas Southwestern Medical Center used extended pluripotent stem cells, which are cells that have the potential, like an embryo, to develop into any type of tissue in the body. These master cells are able to form all three major types of cell groups (ectoderm, endoderm, and mesoderm). Unlike simple pluripotent stem cells, the extended variety can develop into tissues that support the embryo, such as the placenta.Without this type of stem cells, embryos cannot develop and grow properly.

The researchers coaxed stem cells to form into all the cells required for the development of an embryo by bathing them into a solution made of nutrients, growth stimulants, and signaling molecules. The cells assembled into embryo-like structures, including placental tissue.

Next, the artificial embryos were implanted into the uteruses of female mice. Only 7% of the implants were successful but those embryos that did work actually started developing early fetal structures. There were major malformations, however, as the tissue structure and organization did not closely resemble that of a normal embryo.

Previously, other research groups had managed to grow artificial embryos but this was the first time that they were successfully implanted and developed placental cells.

In the future, the University of Texas researchers plan on refining their method in order to grow fetuses that are indistinguishable from normal ones. The goal is to replace real embryos and make artificial ones at scale. These embryo models could then be grown in dishes to study early mammalian development and accelerate drug development.

Some of the cells that the researchers used to grow into embryos originally came from the ear of a mouse. Theoretically, the same should be possible for human embryos, but why would we? Besides testing drugs, artificial embryos could be grown from the skin cells of an infertile person. Then, in the lab, these embryos could be studied in order to identify potential genetic defects that might cause infertility.

Even if such stem cell-derived embryos do not completely mimic normal embryo growth, there is still a lot we can learn about mammalian development. But, as is always the case with research that breaks the frontiers of what was once thought possible, our policies havent yet kept up with advances. There are serious ethical considerations to possibly making a person from a synthetic embryo. Although such a prospect is still science fiction, rapid developments such as the present study suggest that it is not impossible and we better prepare.

The findings were reported in the journal Cell.

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Novel Cell Sorting and Separation Markets, 2030 – Yahoo Finance

DUBLIN, Oct. 7, 2019 /PRNewswire/ -- The "Novel Cell Sorting and Separation Market: Focus on Acoustophoresis, Buoyancy, Dielectrophoresis, Magnetophoretics, Microfluidics, Optoelectronics, Traceless Affinity and Other Technologies, 2019-2030" report has been added to ResearchAndMarkets.com's offering.

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The Novel Cell Sorting and Separation Market: Focus on Acoustophoresis, Buoyancy, Dielectrophoresis, Magnetophoretics, Microfluidics, Optoelectronics, Traceless Affinity, and Other Technologies, 2019-2030' report features an extensive study of the current landscape and future outlook of the growing market for novel cell sorting and separation technologies (beyond conventional methods). The study presents detailed analyses of cell sorters, cell isolation kits, and affiliated consumables and reagents, that are based on the aforementioned technologies.

Advances in the fields of cell biology and regenerative medicine have led to the development of various cell-based therapies, which, developers claim, possess the potential to treat a variety of clinical conditions. In 2018, it was reported that there were more than 1,000 clinical trials of such therapies, being conducted across the globe by over 900 industry players.

Moreover, the total investment in the aforementioned clinical research efforts was estimated to be around USD 13 billion. Given the recent breakthroughs in clinical testing and the discovery of a variety of diagnostic biomarkers, the isolation of one or multiple cell types from a heterogenous population has not only become simpler but also an integral part of modern clinical R&D. The applications of cell separation technologies are vast, starting from basic research to biological therapy development and manufacturing.

However, conventional cell sorting techniques, including adherence-based sorting, membrane filtration-based sorting, and fluorescence- and magnetic-based sorting, are limited by exorbitant operational costs, time-consuming procedures, and the need for complex biochemical labels. As a result, the use of such techniques has, so far, been restricted in the more niche and emerging application areas.

Amongst other elements, the report features:

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Novel Cell Sorting and Separation Markets, 2030 - Yahoo Finance

Platelet BioGenesis Receives Contract Worth Up to $56 Million from the Biomedical Advanced Research and Development Authority (BARDA) to Develop Human…

CAMBRIDGE, Mass.--(BUSINESS WIRE)--

Funding will support clinical development of stem cell-derived platelet technology platform

Platelet BioGenesis, Inc. (PBG), the leader in stem cell-derived, on-demand human platelets (PLTs+) and genetically engineered platelet-based therapeutics, announced today it was awarded a contract worth $5 million, with the potential to reach $56 million total with options, by the Biomedical Advanced Research and Development Authority (BARDA), an agency of the US government's Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response. PBG will use the funding to develop and establish donor-independent platelets as a medical countermeasure for treating victims of a nuclear or radiological event.

As part of national biodefense preparedness, BARDA has prioritized the development and procurement of therapies for trauma resulting from chemical, biological, radiological and nuclear defense threats, including exposure to high doses of radiation. BARDA, with its extensive experience working with organizations focused on blood-related therapies, has evaluated PBGs technology platform and determined that donor-independent platelets could be a critical medical countermeasure in case of a national threat.

This is a significant milestone for PBG and a highly valuable and timely validation of the groundbreaking work of our scientific founder, Dr. Jonathan Thon, and the research, development and manufacturing teams at PBG, allowing us to use human induced pluripotent stem cells to manufacture platelets on-demand, said Sam Rasty, Ph.D., President and CEO of Platelet BioGenesis. With BARDAs expertise in the development of blood-related therapies, their decision to award us this significant contract will further bolster the companys resources to advance this technology into the clinic. The funding will not only help bring our unique donor-independent platelets to patients as a medical countermeasure but will also expedite the advancement of our broader donor-independent PLTs+ platform.

In a radiological or nuclear emergency, impacted communities will face a significant blood product shortage, explained BARDA Director Rick Bright, Ph.D. We are exploring donor-independent platelet technology to increase surge capacity within the blood industry. Our nation must find innovative ways to make essential blood products available to save lives in any type of mass casualty incident.

PBGs research, development and manufacturing activities under the contract will specifically focus on the development of PLTs+ for the treatment of thrombocytopenia induced by exposure to nuclear radiation. In addition to the funding, BARDA will provide a comprehensive, integrated portfolio approach through mentorship, the facilitation of future partnerships and the enablement of government collaborations with agencies such as the FDA.

About Platelet BioGenesis

Platelet BioGenesis (PBG) has created the only platform that can generate human platelets at scale. The stem cell-derived, on-demand platelets will be the first donor-independent source of platelets to address the chronic shortage worldwide. The company is also developing genetically engineered platelet-based therapeutics, a new treatment modality for cancer and other life-threatening diseases. PBGs platform is patented and cGMP-compliant. The company was spun out of Harvard University and has received venture funding from Qiming Venture Partners USA, Ziff Capital Partners and other investors and obtained grant funding from the Massachusetts Life Sciences Center, the National Institutes of Health and the U.S. Department of Defense. Learn more at plateletbiogenesis.com and follow us on Twitter @plateletbio.

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Researchers identify molecular process that could accelerate recovery from nerve injuries – UCLA Newsroom

Twenty million Americans suffer from peripheral nerve injuries, which can be caused by traumas such as combat wounds and motorcycle crashes as well as medical disorders including diabetes. These injuries can have a devastating impact on quality of life, resulting in loss of sensation, motor function and long-lasting nerve pain. The body is capable of regenerating damaged nerves, but this process is slow and incomplete.

Now, researchers at theEli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLAhave discovered a molecular process that controls the rate at which nerves grow both during embryonic development and recovery from injury throughout life.

The study, led by senior author Samantha Butler and published in the Journal of Neuroscience, used experiments with mice to show that it is possible to accelerate peripheral nerve growth by manipulating this molecular process. The finding could inform the development of therapies that reduce the time it takes for people to recover from nerve injuries.

The human bodys nervous system is comprised of two components: the central nervous system, which includes the brain and spinal cord; and the peripheral nervous system, which encompasses all other nerves in the body. Peripheral nerves extend over long distances to connect limbs, glands and organs to the brain and spinal cord, sending signals that control movement via motor neurons, and relaying information such as pain, touch and temperature via sensory neurons.

Unlike the nerves in the brain and spinal cord, which are protected by the skull and vertebrae, the nerves of the peripheral nervous system have no such protection, leaving them vulnerable to injury. While the body has a mechanism to help peripheral nerves reestablish connections after injury, this process is slow; damaged nerves regrow at an average rate of just one millimeter per day.

The glacial pace of this recovery can take a tremendous toll on peoples lives, as they may have to live with impaired movement and sensation for many months or years.

People with severe peripheral nerve injuries often lose sensation, which makes them susceptible to further injury, and they lose mobility, which can lead to muscle atrophy, said Butler, who holds the Eleanor I. Leslie Chair in PioneeringBrainResearch in the neurobiology department at theDavid Geffen School of Medicine at UCLA. The process of nerve regrowth can be extremely painful and if muscles have atrophied it requires a lot of physical therapy to regain function. My lab seeks methods to accelerate this healing process.

In a 2010 study in mice, Butler and her colleaguesdiscoveredthey could control the rate at which nerves grow in the spinal cord during embryonic development by manipulating the activity of a gene called LIM domain kinase 1, or Limk1. Limk1 controls the rate of nerve growth by regulating the activity of a protein called cofilin. Cofilin plays a key role in a process known as actin polymerization, or treadmilling, which enables nerves to extend thread-like projections over long distances to form neural networks.

Butlers new paper builds on these findings by showing that Limk1 and cofilin also control the rate of growth of peripheral nerves during both development and regeneration.

We discovered that one of the first things a nerve does after injury is switch on all these early developmental molecules that controlled how it grew in the first place, said Butler, who is a member of the UCLA Broad Stem Cell Research Center. Its somewhat similar to how an adult in crisis might reach out to their childhood friends to renew themselves.

In preclinical tests using mouse models with peripheral nerve injuries, Butlers lab showed that this molecular process can be manipulated to make nerves grow faster. Specifically, they found that mice that were genetically engineered so that the Limk1 gene was removed exhibited a 15% increase in the speed of nerve regrowth following injury.

This is a modest improvement for a mouse but one that could translate into a major improvement for a human because our nerves have so much farther to grow, said Butler, who noted that nerves regrow at the same rate in both mice and humans.

This increased rate of nerve regrowth resulted in faster recovery of both motor and sensory functions as measured by how fast the injured mice regained the ability to walk and the sensation in their paws. This is significant because sensory function can take longer than motor function to recover after a traumatic injury, yet sensory function is critical to quality of life.

As a next step, Butler and her lab are using human stem cell-derived motor neurons to screen for drug candidates that could modify this molecular process and speed nerve regeneration in humans. They are also expanding the scope of their study by examining if adding more cofilin rather than inhibiting Limk1 could be even more effective in speeding up recovery from peripheral nerve injuries.

The experimental treatment model described above was used in preclinical tests only and has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

Funding for this study was provided by the National Institutes of Health, the Craig H. Neilsen Foundation, the Merkin Family Foundation and the UCLA Broad Stem Cell Research Center Research Award Program, supported by the Jean Perkins Foundation.

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Researchers identify molecular process that could accelerate recovery from nerve injuries - UCLA Newsroom

A Therapeutic Counterblow to Traumatic Brain Injury – Technology Networks

A blow to the head or powerful shock wave on the battlefield can cause immediate, significant damage to a person's skull and the tissue beneath it. But the trauma does not stop there. The impact sets off a chemical reaction in the brain that ravages neurons and the networks that supply them with nutrients and oxygen.

It is the secondary effects of traumatic brain injury (TBI), which can lead to long-term cognitive, psychological and motor system damage, that piqued the interest of a team of NJIT biomedical engineers. To counter them, they are developing a therapy, to be injected at the site of the injury, which shows early indications it can protect neurons and stimulate the regrowth of blood vessels in the damaged tissue.

The challenge, researchers say, is that brain cells don't regenerate as well as other tissues, such as bone, which may be an evolutionary strategy for preserving the synaptic connections that retain memories. To date, there is no effective treatment for restoring damaged neurons. The body's protective mechanisms also make it difficult to penetrate the blood-brain barrier, which hampers the delivery of medications.

"Nerve cells respond to trauma by producing excessive amounts of glutamate, a neurotransmitter that under normal conditions facilitates learning and memory, but at toxic levels overexcites cells, causing them to break down. Traumatic brain injury can also result in the activation and recruitment of immune cells, which cause inflammation that can lead to short- and long-term neural deficits by damaging the structure around cells and creating a chronic inflammatory environment," says Biplab Sarkar, a post-doctoral fellow in biomedical engineering and member of the team that presented this work at a recent American Chemical Society conference.

The team's treatment consists of a lab-created mimic of ependymin, a protein shown to protect neurons after injury, attached to a delivery platform -- a strand of short proteins called peptides, contained in a hydrogel -- that was developed by Vivek Kumar, director of NJIT's Biomaterial Drug Development, Discovery and Delivery Laboratory. After injection, the peptides in the hydrogel reassemble at the localized injury site into a nanofibrous scaffold that mimics extracellular matrix, the supporting structure for cells. These soft materials possess mechanical properties similar to brain tissue, which improves their biocompatibility. They promote rapid infiltration by a variety of stem cells which act as precursors for regeneration and may also provide a biomimetic niche to protect them.

Now in preclinical animal trials, rats injected with the hydrogel retained twice as many functioning neurons at the injury site as compared to the control group. They also formed new blood cells in the region.

"The idea is to intervene at the right time and place to minimize or reverse damage. We do this by generating new blood vessels in the area to restore oxygen exchange, which is reduced in patients with a TBI, and by creating an environment in which neurons that have been damaged in the injury are supported and can thrive," Kumar says. "While the exact mechanism of action for these materials is currently under study, their efficacy is becoming apparent. Our results need to be expanded, however, into a better understanding of these mechanisms at the cellular level, as well as their long-term efficacy and the resulting behavioral improvements."

Collaborators James Haorah, an associate professor of biomedical engineering, and his graduate student Xiaotang Ma at NJIT's Center for Injury Biomechanics, Materials and Medicine have shown how a number of TBI-related chemical effects can disrupt and destroy integral brain vasculature in the blood-brain barrier, the brain's protective border, promoting chronic inflammation that can lead to symptoms such as post-traumatic stress disorder and anxiety, among others. Their current work provides insights into the potential neuroprotective and regenerative response guided by the Kumar lab's materials, while future studies will attempt to analyze other mediators of inflammation and blood flow in the brain.

Kumar's delivery mechanism is a customizable, Lego-like strand made of short proteins called peptides, which are composed of amino acids, with a biological agent attached at one end that can survive in the body for weeks and even months, where other biomaterials degrade quickly. Its self-assembling bonds are designed to be stronger than the body's dispersive forces; it forms stable fibers, with no signs of inducing inflammation, that rapidly incorporate into specific tissues and collagen, recruiting native cells to infiltrate. The hydrogel, which is also composed of amino acids, is engineered to trigger different biological responses depending on the payload attached. These platforms can deliver drugs and other small cargo over day-, week- or month-long periods. Kumar's lab has recently published research on applications ranging from therapies to prompt or prevent the creation of new blood vessel networks, to reduce inflammation and to combat microbes.

"The ultimate hope is that that localized delivery of regenerative materials may provide significant benefits for a number of pathologies," he notes.

For example, the team recently developed a class of materials that may be useful against infection. These novel anti-microbial peptides are capable of disrupting dense bacterial colonies and have shown promise against a number of yeasts. Additionally, they promote human cell proliferation and are currently being studied for wound healing. That work was published this summer in the journal ACS Biomaterials Science and Engineering.

Kumar and his lab have created another hydrogel designed to recruit autologous (a person's own) dental pulp stem cells directly to the disinfected cavity after root canal therapy. The tooth would be regenerated in part by prompting growth of the necessary blood vessels to support the new tissue. Yet another peptide-based therapy, armed with antiangiogenic capabilities, targets diabetic retinopathy, an ocular disease affecting more than 90 million people worldwide. People with the disease form immature blood vessels in the retina, obstructing their vision. The hydrogel can be injected directly into the vitreous gel of the eye, where the peptide interacts with the endothelial cells in the aberrant blood vessels, causing them to die.

"Conventional biomaterials used in tissue regeneration suffer from a variety of problems with delivery, retention and biocompatibility, which can lead to rejection by the host," Kumar says. "We're trying to address these issues with a technology designed to be universal in its application, delivering materials that persist in the tissue and promote their biologic effects for long periods of time."

Reference: Sarkar et al. 2019.Membrane-Disrupting Nanofibrous Peptide Hydrogels. ACS Publications. DOI: https://doi.org/10.1021/acsbiomaterials.9b00967.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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A Therapeutic Counterblow to Traumatic Brain Injury - Technology Networks

American Cancer Society research breakfast highlights Colorado innovations changing the face of cancer care – The Know

On October 1, the American Cancer Society (ACS) Cancer ActionNetwork (CAN) along with presenting sponsors University of Colorado CancerCenter and UCHealth hosted more than a hundred leaders from business,education, government, and research communities to answer an interesting question:What do a highly successful new treatment against leukemia stem cells, a newway to point the immune system at pediatric cancer cells, and new understandingof how Medicare expansion affects cancer outcomes have in common? The answer:All three are born in Colorado. Due in part to new investments in infrastructureand the recruitment of top talent, combined with a climate of collaboration andinnovation, CU Cancer Center researchers are at the forefront of discoveries andinitiatives that are driving a golden age of cancer prevention, research, andcare.

Delivering quick welcome messages were representatives from the offices of Senator Michael Bennet, Senator Cory Gardner, and Representative Jason Crow, along with RJ Ours, Colorado Government Relations Director for ACS CAN. Attendees included John J. Reily, Jr., MD, Dean of the University of Colorado School of Medicine, and Don Elliman, Chancellor of the University of Colorado Anschutz Medical Campus.

Wereworking today to strengthen Colorados network of people collaborating to fightcancer so that you have the new tools and resources to accelerate the pace of discoveryduring this significant period of change, opportunity, and promise to endcancer as a health problem, Ours said, setting the tone.

Leading the mornings program was CU Cancer Center Director,Richard Schulick, MD, who spoke about the burden of cancer, the strategies weuse to attack it, and the activities across the CU Cancer Center consortium todevelop new strategies for cancer prevention, early detection, treatment,education, and access to care.

Im here not only as the cancer center director, but as the sonof two parents who developed cancer during their lifetimes. My passion comesfrom very personal experience, Schulick said. What is our goal? For the peoplein this room, the goal is to eradicate the pain and suffering from cancer.

Despite a 26 percent reduction in the death rate of peoplediagnosed with cancer over the previous 25 years, there remains a long way togo toward Schulicks goal. In the next decade, cancer is set to overtake heartdisease as the leading cause of death in the United States. About 1.7 million Americanswill be diagnosed with dangerous cancer this year, and 600,000 will pass fromthe disease, over 8,000 in Colorado alone. Lifetime cancer risk is about 40percent and the risk of dying from cancer is about 20 percent.

I cant imagine a more pressing problem we need to deal with a society,a research institution, and as a community, Schulick said.

In addition to innovative, new treatments, Schulick says manygains will come from learning to better use existing treatments. For example, thetraditional workflow of cancer care starts with a primary care physician, whorefers a patient to an oncology specialist, who may send the patient a weeklater for diagnostic imaging, then a week later to consult with a surgeon, who sendsthe patient to a radiologist, etc. all of which results in many appointmentsover the course of weeks or months just to decide on a course of care. Instead,at CU Cancer Center care partners, patients may be seen in multidisciplinaryclinics.

Its a better model for taking care of cancer patients, Schulicksays. They come in the morning, get a physical exam and any needed imaging, seea nutritionist, a pain specialist, etc. Thenall the doctors and specialists meet from noon to one and go over everything,typically with 30 or more people in the room. Everyone is there, they all weighin and argue about the best treatment plan. Then the whole team meets with thepatient, all at the same time. In one day, everything is done, the whole treatmentplan laid out. Patients love this and their families love it even more.

Now a major goal is to expand access to the best cancer care topatients outside the Denver metro area.

Were trying to make the very best care available to every citizenin Colorado and surrounding states, no matter where they live. Its no good ifwe have all the best therapies and clinical trials concentrated only on thiscampus that doesnt do any good for a lot of people who cant get here. So wehave to spread our ability to care for these patients, Schulick says.

The second presentation highlighted this need for additional services to reach Colorados rural and underserved populations.

Cathy Bradley, PhD, CU Cancer Center deputy director, pointed out that the lung cancer survival rate for patients living in the Front Range is 70 percent, while the survival rate for Coloradans living in rural and high-poverty areas is only 55 percent. Likewise, rates of HPV vaccination that can effectively prevent cervical cancer are 45 percent in Colorado as a whole, but only 28 percent in rural areas.

These disparities are wider than they are elsewhere, Bradleysays. Our white population does better than whites nationally, while our Hispanicsdo worse than Hispanics nationally. And the Colorado youth vaping rate is fourtimes the national average.

Bradley also pointed out the benefit in focusing on cancerprevention, pointing out that while $500,000 could help 3,000 people becomenon-smokers, or screen 700 people for lung cancer, or screen 1,200 people forcolon cancer, the same amount of money is only enough to treat 4-8 people withadvanced cancers.

Until recently, one of the worst of these advanced cancer wasacute myeloid leukemia (AML).

AML is an absolute monster of a disease, one of the mostaggressive forms of cancer known to man. Until a couple years ago, they neverwould have invited someone like me to a breakfast like this: I would have beentoo depressing. Thats all changed in the last couple years, says Daniel A. Pollyea, MD, MS, the Robert H. AllenEndowed Chair in Hematology Research and clinical director of Leukemia Servicesat the CU School of Medicine.

Based on CU Cancer Center basic science, Pollyea and colleagueshave built a hematology program specifically focused on targeting leukemia stemcells.

Its population of cells that cant be killed with chemo and thatcauses relapse, Pollyea says. We believed that if we could kill leukemia stemcells, maybe we could even cure the disease.

The treatment that Pollyea was able to offer to Colorado patientsthrough clinical trials in 2015 earned FDA approval in 2018.

Patients here were essentially getting a treatment of the future,kind of time traveling years into the future to get a therapy that wasntavailable then. Thats what so incredible about being a clinician who works inresearch the hope we could deliver a treatment of the future to a patient today,Pollyea says.

Now new trials at CU Cancer Center are refining Pollyeas treatmentand showing that targeting cancer stem cells may have applications for morepeople with AML and perhaps even beyond leukemia.

At other places, it can be like, Weve never done this before sowere not going to do it now. Here at CU, its more like, Weve never donethat before so lets figure out how to make it happen, Pollyea says.

One of these new things we are just figuring out is how to makehappen is engineering a patients own T cells to attack cancer, which is thespecialty of the mornings third speaker, Terry Fry, MD, CU Cancer Centerinvestigator and co-director of the Human Immunology and ImmunotherapyInitiative at Childrens Hospital Colorado.

I was happy with my career at the National Institutes of Health,Fry says. I had developed a good team, and when Lia Gore [of CU Cancer Centerand Childrens Hospital Colorado] called me to take a look, it was sort of a, Oh,okay, Ill take a look. But from my first visit, it was pretty clear that Coloradowas the place I wanted to be to develop the next generation of immunotherapy.

The first generation of immunotherapies was developed more than acentury ago, when a doctor named William Coley noticed that some cancerpatients who developed infections actually had better cancer outcomes in rarecases, an activated immune system would attack tumor tissue. Then radiation andchemotherapy showed more promise, and anti-cancer immunotherapy went on theback burner for many decades. Terry Fry is a pioneer in the generation ofscientists who revived the idea, often despite naysaying by many in theresearch community who thought it would never pan out.

I just heard Jimmy Carter is celebrating his 95thbirthday today. He was one of the first recipients of immunotherapy for braincancer, Fry says.

But while Jimmy Carters treatment was meant to remove a kind ofbraking system that kept the immune system from attacking cancer, Fryspecializes in the design and testing of treatments that engineer the bodysimmune system T cells to recognize and attack cancer cells.

Ive been privileged to be part of a field called geneticallymodified T cell therapy, or CAR-T cell therapy. Fifteen or twenty years ago, nobodywould have ever thought that it would be possible to take T cells frompatients, genetically modify them to see proteins on the surface of cancer cells,and then reinfuse them as a drug to target cancer, he says.

Still, major challenges remain for CAR-T therapy. Despite beingable to induce remission in 80 percent of pediatric patients with B-cellleukemia, about 50 percent will relapse within the first year.

I certainly dont feel like were done, Fry says. This is atherapy that is very, very new for us in the field of cancer treatment, and westill need to improve induction rate, durability, and the ability to deliver thetreatment safely.

Another challenge for CAR-T therapy is cost, an issue brought upby the first question delivered to the panel by a parent whose daughter hadbeen treated at UCHealth University of Colorado Hospital.

For a long time, the whole conversation was about therapy success,and now people are starting to talk about the challenge of access, Fry says. Thecost of CAR-T is about three or four-hundred thousand per treatment, so its areal challenge that we need to figure out. One thing being discussed is thatthe standard treatment is chemo and bone marrow transplant, which costs morethan $500K and we pay for that now. If we can do this therapy the right way,theres a possibility it could replace another expensive therapy. Also, a lotof work is being done to bring down the cost of these treatments.

The next question asked about research into the rising rate ofcolorectal cancer diagnosed in adults below age 50.

Right now, in my inbox is data describing Colorado rates ofcolorectal cancer in people under 50, says Cathy Bradley. Its something wereaware of as a problem and is just starting to get attention nationally.

Schulick pointed out that the American Cancer Society is leading apush to lower the recommended age to start colorectal cancer screening from 50to 45. The question is whats the cost and what are the lives saved, Schulicksays, but I think theres enough evidence now to lower the screening age.Another frontier is genetic risk. The idea is that maybe if you have a certainpanel of genes, you have your first colonoscopy at age 20 or 30 or 40. I thinkthe frontiers are being pushed and were learning more about genetics and riskfactors and how to implement screening that saves lives.

Additional questions focused on how federal policies may affectcancer research, including a proposal to increase annual NIH funding by $6 billion,and how Medicare expansion has affected cancer outcomes.

In a study funded by the ACS, we looked at states that expanded Medicareand those that did not, and found that with far more low income women beingscreened, there were fewer late-stage diagnoses, and longer survival, saysBradley. Also, the availability of medications through Medicaid meant that morewere people taking medicines as directed, and more people staying in theworkforce.

These federal policies that affect cancer research and care mayseem abstract, but the ACS closed the morning by offering two ways to getinvolved now: First, ACS Ambassador Martha Cox suggested signing the ACSpetition to increase cancer research funding; second, Cox suggested becominga member of the ACS Cancer Action Network.

Despite significant progress against cancer, there remains muchmore to do. Right now, here in Colorado, we are at an absolute epicenter of researchaimed at the disease. Events like this mornings ACS research breakfast ensurethat everyone in the community of people who care about cancer is aware of thegreat opportunity and also the great responsibility we have to continuepowering this push toward a day when suffering from cancer is no more.

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American Cancer Society research breakfast highlights Colorado innovations changing the face of cancer care - The Know

UW Medicine receives $50 million donation to start brain institute – Lewiston Morning Tribune

SEATTLE A pair of philanthropists from Bellevue have given $50 million to UW Medicine to create an institute focused on developing treatments for brain disorders such as addiction, depression and Alzheimers disease.

The money, donated by Lynn and Mike Garvey, will kickstart the development of the Garvey Institute for Brain Health Solutions.

This will be the second neuroscience-focused institute in Seattle. The Allen Institute for Brain Science examines how the brain works, while the new Garvey Institute will take a more clinical approach to brain health. The work done at each could mesh nicely together, said Dr. Jrgen Untzer, a professor and chairman of UWs psychiatry and behavioral sciences department, which will be home to the Garvey Institute.

Garvey Institute researchers will build on work already being done at UW Medicine, and will also partner with scientists from within the University of Washington and other local health systems, Untzer said.

The goal is not only to develop brain solutions but to get them quickly put into practice, he said.

In addition to clinical research on treatments for brain disorders, the money will also fund training efforts for scientists and researchers from different disciplines at the institute, as well as a place for them to work together.

In its first five years, the Garvey Institute will focus on three main areas: cognitive aging and brain wellness; the effects of physical and emotional trauma on the brain; and addiction.

At some point, almost every family is affected by a brain-health problem such as depression, Alzheimers disease or addiction, Lynn Garvey said in the news release. These diseases are so common and so devastating, and we wanted to do something to help.

The Garveys, who declined to be interviewed, have previously donated money to UW Medicines Institute of Stem Cell and Regenerative Medicine, the psychiatry and behavioral sciences department, Harborview Medical Center, and the heart regeneration and gastroenterology programs.

Mike Garvey is the primary founder of Saltchuk, a Seattle-based family of transportation and distribution companies.

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UW Medicine receives $50 million donation to start brain institute - Lewiston Morning Tribune

UW Medicine receives $50 million donation to start institute to study addiction, Alzheimer’s and more – The Daily World

By Ryan Blethen

The Seattle Times

A pair of philanthropists from Bellevue have given $50 million to UW Medicine to create an institute focused on developing treatments for brain disorders such as addiction, depression and Alzheimers disease.

The money, donated by Lynn and Mike Garvey, will kickstart the development of the Garvey Institute for Brain Health Solutions.

This will be the second neuroscience-focused institute in Seattle. The Allen Institute for Brain Science examines how the brain works, while the new Garvey Institute will take a more clinical approach to brain health. The work done at each could mesh nicely together, said Dr. Jrgen Untzer, a professor and chair of UWs psychiatry and behavioral sciences department, which will be home to the Garvey Institute.

Garvey Institute researchers will build on work already being done at UW Medicine, and will also partner with scientists from within the University of Washington and other local health systems, Untzer said.

The goal is not only to develop brain solutions but to get them quickly put into practice, he said in an interview Wednesday.

In addition to clinical research on treatments for brain disorders, the money will also fund training efforts for scientists and researchers from different disciplines at the institute, as well as a place for them to work together.

These new programs will change the future of mental health and brain health in our region and beyond, Untzer said in a news release announcing the donation.

In its first five years, the Garvey Institute will focus on three main areas: cognitive aging and brain wellness, the effects of physical and emotional trauma on the brain, and addiction.

At some point, almost every family is affected by a brain-health problem such as depression, Alzheimers disease or addiction, Lynn Garvey said in the news release. These diseases are so common and so devastating, and we wanted to do something to help.

The Garveys, who declined to be interviewed, have previously donated money to UW Medicines Institute of Stem Cell and Regenerative Medicine, the psychiatry and behavioral sciences department, Harborview Medical Center, and the heart regeneration and gastroenterology programs.

Mike Garvey is the primary founder of Saltchuk, a Seattle-based family of transportation and distribution companies that reports a consolidated annual revenue of nearly $2.75 billion.

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UW Medicine receives $50 million donation to start institute to study addiction, Alzheimer's and more - The Daily World