20(R)-Ginsenoside Rg3 Influences Cancer Stem Cell Properties and the E | OTT – Dove Medical Press

Lan Thi Hanh Phi,* Yoseph Toni Wijaya,* Ita Novita Sari, Kwang Seock Kim, Ying-Gui Yang, Min-Woo Lee, Hyog Young Kwon

Soonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, Cheonan, Republic of Korea

*These authors contributed equally to this work

Correspondence: Hyog Young Kwon; Min-Woo LeeSoonchunhyang Institute of Medi-Bio Science (SIMS), Soonchunhyang University, 25 Bongjeong-ro, Cheonan, Chungcheongnam-do 31151, Republic of KoreaTel +82-41-413-5021; +82-41-413-5029Email hykwon@sch.ac.kr; mwlee12@sch.ac.kr

Background: Cancer stem cells (CSCs) have been proposed as central drivers of cancer relapse in many cancers. In the present study, we investigated the inhibitory effect of 20(R)-Ginsenoside Rg3 (Rg3R), a major active component of ginseng saponin, on CSC-like cells and the Epithelial-Mesenchymal Transition (EMT) in colorectal cancer (CRC).Methods: The effects of ginsenoside Rg3R on the colony-forming, migration, invasion, and wound-healing abilities of CRC cells were determined in HT29 and SW620 cell lines in vitro. Further, ginsenoside Rg3R was given intraperitoneally at 5mg/kg of mouse body weight to check its effect on the metastasis of CRC cells in vivo.Results: Ginsenoside Rg3R significantly inhibited CSC properties, but did not affect cell proliferation. Moreover, ginsenoside Rg3R treatment significantly inhibited the motility of CRC cells based on migration, invasion, and wound-healing assays. The inhibitory effects of ginsenoside Rg3R on CRC are potentially mediated by significant down-regulation of the expression of stemness genes and EMT markers in CRC cells in a SNAIL-dependent manner. Furthermore, ginsenoside Rg3R treatment decreased both the number and size of tumor nodules in the liver, lung, and kidney tissues in a metastasis mouse model.Conclusion: These findings highlighted the potential use of ginsenoside Rg3R in clinical applications for colorectal cancer treatment.

Keywords: colorectal cancer, ginsenoside Rg3R, CSCs, EMT

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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20(R)-Ginsenoside Rg3 Influences Cancer Stem Cell Properties and the E | OTT - Dove Medical Press

Immunotherapy drug improves outcomes for some children with relapsed leukemia – National Institutes of Health

News Release

Tuesday, December 10, 2019

New findings from a clinical trial show that treatment with the immunotherapy drug blinatumomab is superior to standard chemotherapy for children and young adults with high- or intermediate-risk B-cell acute lymphoblastic leukemia (B-ALL) that has relapsed. Those treated with blinatumomab had longer survival, experienced fewer severe side effects, had a higher rate of undetectable residual disease, and were more likely to proceed to a stem cell transplant.

Our study demonstrates that immunotherapy with blinatumomab is more effective and less toxic than chemotherapy as a bridge to curative bone marrow transplant for children and young adults with very aggressive relapse of B-ALL, said Patrick Brown, M.D., who chaired the trial and is director of the Pediatric Leukemia Program at the Johns Hopkins Kimmel Cancer Center, Baltimore. We are thrilled that these patients, whose survival has not substantially improved for decades, now have a new and better standard of care.

The findings were presented as a late-breaking abstract at the American Society of Hematology (ASH) annual meeting on Dec. 10, 2019. The trial was led by the Childrens Oncology Group (COG), part of the National Cancer Institute (NCI)sponsored National Clinical Trials Network. NCI is part of the National Institutes of Health. Amgen reviewed the trial protocol and amendments and provided the study drug under a Cooperative Research and Development Agreement with NCI.

These findings will likely have immediate impact on the treatment of this group of children and young adults with relapsed B-ALL, said Malcolm Smith, M.D., Ph.D., associate branch chief for pediatric oncology in NCIs Cancer Therapy Evaluation Program, which sponsored the trial. These results also reinforce the important role that federally funded clinical trials play in developing more effective treatments for children with cancer.

When children have B-ALL that relapses after their initial treatment, they are typically given chemotherapy. The first four to six weeks of chemotherapy, the reinduction phase, is commonly followed by additional intensive chemotherapy, or consolidation treatment, to further reduce disease levels. Following this, hematopoietic stem cell transplant is considered the best treatment for approximately half of patients, based on factors such as whether relapse occurred during initial treatment or shortly after it was completed.

However, chemotherapy can produce severe side effects in some patients and is sometimes ineffective in reducing leukemia levels to the low levels needed prior to transplant. As a result, patients may not be able to proceed to transplant or transplant may be delayed, which increases the risk that the leukemia will return.

The COG study investigated blinatumomab as an alternative type of consolidation treatment to follow the reinduction phase. Blinatumomab is a type of immunotherapy that works by binding to two different molecules: CD19, a protein, or antigen, expressed on the surface of B-ALL cells, and CD3, an antigen expressed on T cells. By bringing T cells close to leukemia cells, the immunotherapy helps the T cells recognize and kill the cancer cells.

Blinatumomab has been approved by the U.S. Food and Drug Administration (FDA) for adults and children with B-ALL that has returned or has not responded to treatment. FDA has also granted accelerated approval to the drugmeaning confirmatory trials must show it has clinical benefitfor some adults and children undergoing treatment for B-ALL who achieve complete remission but still have small amounts of leukemia detectable using very sensitive methods.

Investigators in this study wanted to see if blinatumomab could increase rates of survival free from leukemia and be less toxic than intensive chemotherapy in children and young adults undergoing consolidation treatment.

The trial report was based on 208 children and young adults aged 130 with relapsed B-ALL who had received reinduction chemotherapy and were considered to have high- or intermediate-risk disease. They were randomly assigned to receive either two rounds of intensive chemotherapy or two 4-week rounds of treatment with blinatumomab before proceeding to a transplant. (A separate part of the study addressed children with low-risk disease.)

After a median follow-up time of 1.4 years, those in the blinatumomab group had higher rates of 2-year disease-free survival, the primary outcome of the study, than those who received intensive chemotherapy (59.3 5.4% vs. 41 6.2%). Those treated with blinatumomab also had higher rates of overall survival (79.4 4.5% vs. 59.2 6%), fewer severe side effects, a higher rate of undetectable residual disease (79% vs. 21%), and a higher rate of proceeding to stem cell transplant (73% vs. 45%).

At a planned interim analysis, an independent data safety monitoring committee concluded that the outcome for children treated with blinatumomab was superior to that of children treated with chemotherapy only and recommended that enrollment to the high- and intermediate-risk part of the trial be stopped.

Future clinical trials will study whether blinatumomabs effects in relapsed B-ALL can be enhanced by combining it with other immunotherapy and will test whether adding the drug to standard chemotherapy for children and young adults with newly diagnosed B-ALL is beneficial.

About the National Cancer Institute (NCI):NCIleads the National Cancer Program and NIHs efforts to dramatically reduce the prevalence of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI website atcancer.govor call NCIs contact center, the Cancer Information Service, at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health


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Immunotherapy drug improves outcomes for some children with relapsed leukemia - National Institutes of Health

Patients closer to receiving regenerated tissue, scientists say – The Irish News

Doctors are one step closer to using regenerated tissue to treat patients due to breakthroughs in stem cell research, according to a new study.

Scientists have developed a new gel from piglet intestinal tissue to grow tissue in the form of organoids so they can be used in human treatment.

Organoids are laboratory-grown structures of human stem cells that model the shape and function of tissue such as muscle.

While they hold potential for use in the replacement and repair of damaged or diseased tissue, the gels currently used to culture human organoids have been unsuitable for use in patients.

However, the researchers led by National Institute for Health Research Professor Paolo De Coppi and Professor Nicola Elvassore, at University College London Great Ormond Street Institute of Child Health, have developed an extracellular-matrix (ECM) hydrogel.

The use of decellularised piglet intestinal tissue means organoids could be suitable for use in human treatment.

Published in Nature Communications, the study suggests the new hydrogel meets good practice standards so can be used in a clinical setting.

It provides the same level of support to stem cells in the organoid culture as synthetic gels, scientists say.

Gels used in the development of organoids play an important role in determining the final tissue that is grown.

Researchers found their new ECM hydrogel could be used to support cell growth not only in small intestine tissue, but also for liver, stomach and pancreatic tissue.

They say their findings mark a step towards clinicians being able to use laboratory-developed organoids in clinical settings.

Prof De Coppi said: There is a huge potential for organoids to open up regenerative medicine and advance how we treat complex conditions.

Our findings mark a major step towards seeing tissue grown from stem cells being used in clinical settings to treat patients.

This could open up the possibility of providing organoid transplants for patients affected by devastating diseases such as short bowel syndrome to improve intestinal function.

Research was conducted by a team from UCL GOS ICH, the Francis Crick Institute, ShanghaiTech University, the Royal Netherlands Academy of Arts and Sciences, University Medical Centre Utrecht, Princess Maxima Centre for Paediatric Oncology Netherlands and the Telethon Institute of Genetics and Medicine in Italy.

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Patients closer to receiving regenerated tissue, scientists say - The Irish News

Layoffs at Fla.-based stem cell clinic accused of aggressively marketing patients – ABC Action News

Tampa, Fla. A Tampa-based regenerative clinic accused of using aggressive and unfair marketing tactics to lure the diseased and desperate into spending thousands of dollars on unproven stem cell therapies laid off a small number of non-medical employees earlier this week, a company spokesperson confirmed.

While its unknown exactly how many employees the Lung Health Institute let go of earlier this week, a spokesperson on Wednesday denied the layoffs were the result of a pending lawsuit facing the company and recent media scrutiny questioning its practices. Instead, the spokesperson wrote in a statement the layoffs were the result of a planned transition that aligns with our strategy of moving away from a direct-to-consumer business model and focusing on our goal of ultimately creating industry-leading therapies that are FDA-approved for the treatment of chronic lung disease.

The Lung Health Institute, which is headquartered in Tampa but has locations in four other states, has been criticized by former clients for aggressively pitching stem cell therapies for incurable lung diseases that are not FDA approved or proven to work. In 2018, we spoke with former clients and widows of clients who described how they were pitched therapies for incurable lung diseases.

Hell definitely get some kind of improvement, thats what they told me, said Olga Cassady whose husband died of lung disease about 6 months after, she says, they spent $11,000 for treatment at the institutes Tampa headquarters, formerly known as the Lung Institute.

In 2018, Maureen Rosen of Ocala, also told us how she also bought into the Institutes pitch that its treatment would help slow down her progression with chronic obstructive pulmonary disease (COPD). At the time, Rosen was on an oxygen tank 24/7. But shortly after her treatment at the Lung Institute, Rosen told us, it seems like from the day I had it, I started to get worse, she said last year.

Rosen and Cassady are not the only ones complaining about the treatments offered by the company.

Tampa Attorney Ben Vinson filed the lawsuit on behalf of two former patients and said he has more than 30 others including Rosen and Cassady, who are hoping for a class action lawsuit against the clinic.

In Vinsons original complaint filed in 2017, he accused the Lung Institute of using aggressive and deceptive marketing tactics for sham treatments based on sham science and deception, according to the complaint.

They were desperate when they came to this company. They were all dying slowly, suffocating from various lung illnesses, Vinson said. They were desperate financially, in most cases, to afford the procedure so a lot of them gave up their last dime in order to do so, he said.

Earlier in the day, its spokesperson sent us copies of six testimonials from former patients who said they felt positive results after undergoing treatments at the institute. Several indicated they sought booster treatments after benefits from their original treatments wore off.

According to court filings, before any treatments are done at the institute, patients must sign a patient consent form which warns them that the treatment may not have any impact on their conditions.

A company spokesperson said the company is currently in discussions with the FDA to start clinical trials with investigative new drugs (IND) to help treat patients with lung diseases.

As for this weeks layoffs and its impact on patient treatments at the Institutes facilities, a company spokesperson said, the changes will have no impact on the quality medical care we provide our patients.

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Layoffs at Fla.-based stem cell clinic accused of aggressively marketing patients - ABC Action News

Global T-Cell Therapy Market: Trends, Opportunities and Forecasts (2019-2026) – Therapy for Solid Tumors Expected to Emerge as a Lucrative Source of…

DUBLIN, Dec. 11, 2019 /PRNewswire/ -- The "T-Cell Therapy Market Size, Share & Trends Analysis Report By Modality, By Therapy (CAR T-Cell, Tumor Infiltrating Lymphocytes), By Indication (Hematologic Malignancies, Solid Tumors), And Segment Forecasts, 2019 - 2026" report has been added to ResearchAndMarkets.com's offering.

The global T-cell therapy market size is expected to reach USD 7.51 billion, expanding at a CAGR of 15.4% by 2026.

The landmark approvals of Yescarta and Kymriah have spurred unprecedented advancements in the market. The launch of these breakthrough therapies has bolstered cash inflow for innovation, thereby driving the growth.

Expansion of the market for T-cell therapy significantly relies on shifting preference from first-line stem cell transplants and chemotherapy to third-line CAR T-cell therapy. Moreover, the ever-expanding plethora of medical conditions for which the T cell therapies is projected to bode well for the market growth. Rise in oncological disorders is projected to drive interest as well as investments in the T-cell therapy market in near future.

In contrast with the small-molecule landscape, engineered T cells market landscape is distinguished by an extensive network that encompasses several entities marked by connections academically, financially, and via technology licensing. Research bodies, and manufacturers, and regulators engage in assessing the long-term efficacy and safety of therapies to ensure safe access to patients.

By far, the antigen challenge and linked toxicity concerns have impeded the development of CAR T therapies in non-hematological malignancies. Market players are applying a data-driven approach of exploring this space to mitigate the challenge and expand the usage of T-cell therapy in indication type such as brain cancer and melanoma.

Further key findings from the report suggest:

Key Topics Covered

Chapter 1 Research Methodology

Chapter 2 Executive Summary2.1 Competition Milieu2.2 Market Snapshot2.3 Segment Outlook

Chapter 3 Market Variables, Trends, & Scope3.1 Penetration & Growth Prospect Mapping for Therapy Type, 20183.2 T-Cell Therapy-Market Dynamics3.2.1 Market driver analysis3.2.1.1 Rising investment in adoptive T cell transfer approaches of disease treatment3.2.1.2 Growing competition among market players3.2.1.3 Approval of Kymriah and Yescarta across various countries3.2.1.4 Developments in CAR T-cell therapy for solid tumors3.2.1.5 Technological advancements in manufacturing process3.2.2 Market restraint analysis3.2.2.1 Regulatory, scientific, and ethical challenges associated with gene therapy3.2.2.2 High prices of therapies3.2.2.3 CAR T limitations3.2.3 Opportunity analysis3.2.3.1 Facility expansion for cell and gene therapies3.2.3.2 Rising global financings in gene and cell therapy arena3.2.3.3 Ongoing developments in viral & non-viral vector manufacturing arena3.3 Regulatory Landscape3.3.1 Current and potential future approvals3.3.2 Frameworks for risk mitigation and safety monitoring3.3.3 Regulatory framework, by geography3.3.3.1 U.S. Europe3.3.3.3 China3.3.3.4 Japan3.4 Pricing and Payment Models for Adoptive Cellular Therapies (ACT)3.4.1 Insurance coverage3.4.2 Value-based price benchmarks3.4.3 Alternate payment strategies3.5 Patent Landscape3.6 Deals, Funding's, Partnerships and Collaborations3.6.1 Licensing deals3.6.2 Merger & acquisition deals3.6.3 Collaboration & partnerships3.7 Pipeline Analysis3.7.1 Clinical trial landscape3.8 Geographic Mapping of Companies3.9 Competitive Landscape for CD19directed CART Therapies and Other T-cell therapies3.10 T-cell Therapy Market-SWOT Analysis, by Factor (Political & Legal, Economic, and Technological)3.10.1 Political landscape3.10.2 Economic landscape3.10.3 Social landscape3.10.4 Technology landscape3.11 Industry Analysis-Porter's3.11.1 Supplier bargaining power3.11.2 Buyer bargaining power3.11.3 Substitution threat3.11.4 Threat from new entrant3.11.5 Competitive rivalry

Chapter 4 T-cell Therapy Market: Modality Estimates & Trend Analysis4.1 T-cell Therapy Market: Modality Movement Analysis4.2 Research4.3 Commercialized

Chapter 5 T-cell Therapy Market Categorization: Therapy Type Estimates & Trend Analysis5.1 T-cell Therapy Market: Therapy Type Movement Analysis5.2 CAR T-cell Therapy5.3 T Cell Receptor (TCR)-based5.4 Tumor Infiltrating Lymphocytes (TIL)-based

Chapter 6 T-cell Therapy Market Categorization: Indication Estimates & Trend Analysis6.1 T-cell Therapy Market: Indication Movement Analysis6.2 Hematologic Malignancies6.3 Solid Tumors

Chapter 7 T-cell Therapy Market Categorization: Regional Estimates & Trend Analysis, by Use-type & Therapy Type7.1 T-cell Therapy Market Share by Regional, 2018 & 20267.2 North America7.3 Europe7.4 Asia Pacific7.5 Latin America7.6 MEA

Chapter 8 Competitive Landscape8.1 Strategy Framework8.2 Company Profiles8.2.1 Novartis AG8.2.2 Gilead Sciences8.2.3 bluebird bio, Inc.8.2.4 TCR2 Therapeutics Inc.8.2.5 Sorrento Therapeutics8.2.6 Fate Therapeutics8.2.7 Merck KGaA8.2.8 Pfizer Inc.8.2.9 Amgen8.2.10 Celgene Corporation

For more information about this report visit https://www.researchandmarkets.com/r/j88hyn

Research and Markets also offers Custom Research services providing focused, comprehensive and tailored research.

Media Contact:

Research and Markets Laura Wood, Senior Manager press@researchandmarkets.com

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The Knesset dissolves and the public suffers – Ynetnews

After two dramatic rounds of elections, Israel is still without a functioning government, resulting in stagnation, red tape, unbearable bureaucracy, underpaid workers, and in some instances, threat to life.

Among the many hurdles, the people of Israel are left to face by themselves is the stagnation of the bureaucratic systems around the country. The health care committee, for example, has been left not knowing its budget for 2020.

Adam Elgressy

(Photo: Dan Gershoni)

That means that many patients don't know when or even if they will receive their required, often lifesaving treatments and medication.

One such patient is 41-year-old Adam Elgressy, who suffers from Crohn's disease and requires Stem Cell treatment. Even though he has already had no less than 21 operations, he still has one more to go, but he's still doesn't know when he may receive his last treatment.

"Patients like me have real chance to have full lives," says Elgressy. If there's no budget to treat us, we'll be condemned to another year of barely functioning."

Shulamit Schwartz, who suffers from an aggressive form of lung cancer called Small-Cell Carcinoma (SCLC), is hoping that the medication needed to treat her disease will make it onto the list of state-subsidized medications.

Shulamit Schwartz

(Photo: Courtesy)

"The clock for lung cancer patients is ticking," says Schwartz. When you receive the news that you have one of the most aggressive types of cancer, you hear a clock ticking in your ear constantly. We pay the country to take care of us in our adult life, and now is the time for the country to take care of us."

The hospitals are also suffering from the political turmoil, with patients being treated in the hallways, and the staff themselves overworked from extreme shortage in manpower, and even though a Health Ministry committee deliberated on how to improve the situation in hospitals, the political stagnation means that there is no budget to implement any of its findings.

Heavy loads in hospitals

(Photo: Israel Society of Internal Medicine)

"The hospitals have many departments that are at over capacity all year long," says Prof. Avishay Elis, head of the Israel Society of Internal Medicine, who was also part of the committee. "In the report we submitted there are solutions that could be applied immediately, but there's no one left to start applying them."

Israel's education system is another casualty, and although the Education Ministry had plans that were already budgeted at approximately NIS 6 billion, the political state of flux means that these plans are on indefinite hold.

The immediate financial cost will be felt mostly by parents who will now be paying for their children's previously state-funded enrichment programs during the school holidays.

A program for special education students was meant to facilitate the inclusion of children with special needs in regular classrooms was supposed to start in the coming school year, but now that plan has been put on hold as well.

Teachers are, of course, also hurt by the political situation. There is no government to negotiate terms of employment with. We have already said everything there is to say about teachers' employment conditions in Israel," says teacher Rachel Kenan.

Were dealing with low pay, embarrassing pensions, unpaid overtime, and the fact that student teachers need to pay out of their own pocket in order to train as educators."

Rachel Kenan

(Photo: Courtesy)

Those dependent on the embarrassingly low disability stipend protested last February in order to have the sum increased. After widespread protests, the Knesset approved a gradual increase in the money they receive each month.

The law stated that after the initial increase, both the finance and welfare ministers will discuss whether further increase in the disability stipend was needed."

Now those dependent on the increased income are left with no money and no answers.

Razit Ben-Broch is a 41-year old single mother, who is 100% disabled according to Israel's National Insurance Institute.

"I am suffering from Post-Traumic Stress Disorder, and I'm a single mother, every shekel is critical for me, she says. The stipend I'm forced to live on is not nearly enough for me and my daughter, for now, it seems unlikely we'll receive any increase."

Disabeled Israelis protesting in Tel Aviv

(Photo: Yair Sagi)

Ben-Broch added: "I can't give my daughter the life she deserves, it's very sad that this is the life those who suffer from disability are forced to live in Israel."

Young children in need are also left to suffer, with approximately 200 teenagers out in the streets, waiting sometimes more than nine months for a place to open up in one of the few state-funded youth shelters.

In the meantime, these teenagers are left to roam the streets, commit crimes, abuse heavy drugs, and engage in sex work themselves in order to survive, simply because there's no approved budget in order to build additional shelters.

Miriam Peretz was one such girl. She was only 17 when she died of an overdose after waiting for more than nine months for a place to open up in one of the packed youth shelters near Jerusalem.

While she waited, Miriam's situation deteriorated, and she started using heavy drugs more and more frequently. Her life tragically ended after she overdosed in the house of an acquaintance in Jerusalem.

Ironically, those that aren't expected to be affected by the turmoil that has somehow worsened all of our everyday lives are the members of Knesset, who have awarded themselves a 3.5% raise in order to mark the new year.

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The Knesset dissolves and the public suffers - Ynetnews

New Mechanism of Bone Maintenance and Repair Discovered – Technology Networks

Led by researchers at Baylor College of Medicine, a study published in the journal Cell Stem Cell reveals a new mechanism that contributes to adult bone maintenance and repair and opens the possibility of developing therapeutic strategies for improving bone healing.

Adult bone repair relies on the activation of bone stem cells, which still remain poorly characterized, said corresponding author Dr. Dongsu Park, assistant professor of molecular and human genetics and of pathology and immunology at Baylor. Bone stem cells have been found both in the bone marrow inside the bone and also in the periosteum the outer layer of tissue that envelopes the bone. Previous studies have shown that these two populations of stem cells, although they share many characteristics, also have unique functions and specific regulatory mechanisms.

Of the two, periosteum stem cells are the least understood. It is known that they comprise a heterogeneous population of cells that can contribute to bone thickness, shaping and fracture repair, but scientists had not been able to distinguish between different subtypes of bone stem cells to study how their different functions are regulated.

In the current study, Park and his colleagues developed a method to identify different subpopulations of periosteum stem cells, define their contribution to bone fracture repair in live mouse models and identify specific factors that regulate their migration and proliferation under physiological conditions.

Periosteal stem cells are major contributors to bone healing

The researchers discovered specific markers for periosteum stem cells in mouse models. The markers identified a distinct subset of stem cells that contributes to life-long adult bone regeneration.

We also found that periosteum stem cells respond to mechanical injury by engaging in bone healing, Park said. They are important for healing bone fractures in the adult mice and, interestingly, their contribution to bone regeneration is higher than that of bone marrow stem cells.

In addition, the researchers found that periosteal stem cells also respond to inflammatory molecules called chemokines, which are usually produced during bone injury. In particular, they responded to chemokine CCL5.

Periosteal stem cells have receptors molecules on their cell surface that bind to CCL5, which sends a signal to the cells to migrate toward the injured bone and repair it. Deleting the CCL5 gene in mouse models resulted in marked defects in bone repair or delayed healing. When the researchers supplied CCL5 to CCL5-deficient mice, bone healing was accelerated.

The findings suggested potential therapeutic applications. For instance, in individuals with diabetes or osteoporosis in which bone healing is slow and may lead to other complications resulting from limited mobility, accelerating bone healing may reduce hospital stay and improve prognosis.

Our findings contribute to a better understanding of how adult bones heal. We think this is one of the first studies to show that bone stem cells are heterogeneous and that different subtypes have unique properties regulated by specific mechanisms, Park said. We have identified markers that enable us to tell bone stem cell subtypes apart and studied what each subtype contributes to bone health. Understanding how bone stem cell functions are regulated offers the possibility to develop novel therapeutic strategies to treat adult bone injuries.


Ortinau et al. (2019) Identification of Functionally Distinct Mx1+SMA+ Periosteal Skeletal Stem Cells. Cell Stem Cell. DOI: https://doi.org/10.1016/j.stem.2019.11.003

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New Mechanism of Bone Maintenance and Repair Discovered - Technology Networks

Lineage Cell Therapeutics and AgeX Therapeutics Announce Issuance of US Patent for Method of Generating Induced Pluripotent Stem Cells – BioSpace

The issuance of this patent highlights Lineages dominant position in the field of cell therapy, stated Brian M. Culley, CEO of Lineage. Our efforts to develop new treatments rely on well-characterized and NIH-approved human cell lines. These lines are not genetically manipulated, which avoids the safety concerns associated with genetic aberrations arising from the creation of iPS cells. We believe the Lineage cell lines provide the safest option for our current clinical-stage programs, particularly in immune-privileged anatomical sites such as the eye (OpRegen for the treatment of dry AMD) and spinal cord (OPC1, for the treatment of spinal cord injury). However, the vast intellectual property estate which underlies our cell therapy platform has never been limited to these particular cell lines. As one example, this newly-issued patent provides us with proprietary methods for producing induced pluripotent stem cells, or, as it was practiced by us prior to Yamanaka, Analytical Reprogramming Technology (ART). In certain settings, an ART/iPS approach might offer important advantages, such as for an autologous treatment or when the selection of preferential attributes from a series of iPS lines is desirable. Questions as to which stem cell technology is preferred ultimately will be answered by clinical safety and efficacy and likely will be indication-specific, so we believe it is in the best interest of our shareholders to generate patented technology which enables us to pursue programs in either or both formats which we believe will ensure the highest probability of success.

This patent broadly describes multiple techniques for reprogramming cells of the body back to the all-powerful stem cell state, said Dr. Michael D. West, CEO of AgeX and first inventor on the patent. Perhaps more significantly, it includes certain factors that address some of the difficulties currently encountered with iPS cells. It also reflects the foundational work our scientists have undertaken to apply reprogramming technology to age-reversal, specifically, induced Tissue Regeneration (iTR) which is currently a focus of AgeX product development.

Induced Pluripotent Stem Cells (iPS) are typically derived from adult skin or blood cells which have been reprogrammed or induced to retrace their developmental age and regain the potential to form all of the young cell and tissue types of the body. In 2010 inventors of the -723 patent issued today demonstrated that this reversal of developmental aging even extended to the telomere clock of cell aging. This reprogramming technology provides an alternate source of starting material for the manufacture of potentially any type of human cell needed for therapeutic purposes. Because iPSCs can be derived directly from adult tissues, they can be used to generate pluripotent cells from patients with known genetic abnormalities for drug discovery or as an alternative source of cell types for regenerative therapies.

U.S. Patent No. 10,501,723, entitled Methods of Reprogramming Animal Somatic Cells was assigned to Advanced Cell Technology of Marlborough, Massachusetts (now Astellas Institute for Regenerative Medicine) and licensed to Lineage and sublicensed to AgeX Therapeutics for defined fields of use. Inventors of the patent include Michael D. West, CEO of AgeX and previous CEO of Advanced Cell Technology, Karen B. Chapman, Ph.D., and Roy Geoffrey Sargent, Ph.D.

About Lineage Cell Therapeutics, Inc.

Lineage Cell Therapeutics is a clinical-stage biotechnology company developing novel cell therapies for unmet medical needs. Lineages programs are based on its proprietary cell-based therapy platform and associated development and manufacturing capabilities. With this platform Lineage develops and manufactures specialized, terminally-differentiated human cells from its pluripotent and progenitor cell starting materials. These differentiated cells are developed either to replace or support cells that are dysfunctional or absent due to degenerative disease or traumatic injury or administered as a means of helping the body mount an effective immune response to cancer. Lineages clinical assets include (i) OpRegen, a retinal pigment epithelium transplant therapy in Phase I/IIa development for the treatment of dry age-related macular degeneration, a leading cause of blindness in the developed world; (ii) OPC1, an oligodendrocyte progenitor cell therapy in Phase I/IIa development for the treatment of acute spinal cord injuries; and (iii) VAC2, an allogeneic cancer immunotherapy of antigen-presenting dendritic cells currently in Phase I development for the treatment of non-small cell lung cancer. Lineage is also evaluating potential partnership opportunities for Renevia, a facial aesthetics product that was recently granted a Conformit Europenne (CE) Mark. For more information, please visit http://www.lineagecell.com or follow the Company on Twitter @LineageCell.

About AgeX Therapeutics

AgeX Therapeutics, Inc. (NYSE American: AGE) is focused on developing and commercializing innovative therapeutics for human aging. Its PureStem and UniverCyte manufacturing and immunotolerance technologies are designed to work together to generate highly-defined, universal, allogeneic, off-the-shelf pluripotent stem cell-derived young cells of any type for application in a variety of diseases with a high unmet medical need. AgeX has two preclinical cell therapy programs: AGEX-VASC1 (vascular progenitor cells) for tissue ischemia and AGEX-BAT1 (brown fat cells) for Type II diabetes. AgeXs revolutionary longevity platform induced Tissue Regeneration (iTR) aims to unlock cellular immortality and regenerative capacity to reverse age-related changes within tissues. AGEX-iTR1547 is an iTR-based formulation in preclinical development. HyStem is AgeXs delivery technology to stably engraft PureStem cell therapies in the body. AgeX is developing its core product pipeline for use in the clinic to extend human healthspan and is seeking opportunities to establish licensing and collaboration agreements around its broad IP estate and proprietary technology platforms. For more information, please visit http://www.agexinc.com or connect with the company on Twitter, LinkedIn, Facebook, and YouTube.

Forward-Looking Statements

Lineage cautions you that all statements, other than statements of historical facts, contained in this press release, are forward-looking statements. Forward-looking statements, in some cases, can be identified by terms such as believe, may, will, estimate, continue, anticipate, design, intend, expect, could, plan, potential, predict, seek, should, would, contemplate, project, target, tend to, or the negative version of these words and similar expressions. Such statements include, but are not limited to, Lineages exploration of alternative cell therapy platforms. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Lineages actual results, performance or achievements to be materially different from future results, performance or achievements expressed or implied by the forward-looking statements in this press release, including risks and uncertainties inherent in Lineages business and other risks in Lineages filings with the Securities and Exchange Commission (the SEC). Lineages forward-looking statements are based upon its current expectations and involve assumptions that may never materialize or may prove to be incorrect. All forward-looking statements are expressly qualified in their entirety by these cautionary statements. Further information regarding these and other risks is included under the heading Risk Factors in Lineages periodic reports with the SEC, including Lineages Annual Report on Form 10-K filed with the SEC on March 14, 2019 and its other reports, which are available from the SECs website. You are cautioned not to place undue reliance on forward-looking statements, which speak only as of the date on which they were made. Lineage undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.

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Lineage Cell Therapeutics and AgeX Therapeutics Announce Issuance of US Patent for Method of Generating Induced Pluripotent Stem Cells - BioSpace

BMS’ oral maintenance therapy boosts survival in AML patients – PMLiVE

Bristol-Myers Squibb has scored significant overall survival results in a phase 3 trial of its oral maintenance therapy CC-486 in acute myeloid leukaemia patients who have limited treatment options.

The QUAZAR AML-001 study investigated CC-486 in newly-diagnosed AML patients who have achieved remission with intensive induction chemotherapy, are at least aged 55 years and are stem-cell transplant ineligible.

The overall survival benefit was significant, with median OS after 41.2 months of follow-up reaching 24.7 months in the CC-486 treatment arm, compared to 14.8 months for placebo an almost ten month improvement.

During a presentation of the results at the annual ASH 2019 conference, Andrew Wei, from the Alfred Hospital and Monash University, Melbourne, Australia, said: Based on the results of the QUAZAR study, we are excited about the clinical development of CC-486 and the potential to establish maintenance therapy as a new treatment paradigm for patients with AML in first remission.

Relapse-free survival also improved in patients treated with CC-486 10.2 months in the treatment arm compared to 4.8 months for placebo.

The study could have a practice-changing impact on the treatment of older AML patients who have a poor prognosis, according to Robert Brodsky, a professor of medicine at Johns Hopkins University in the US.

BMS took on the candidate following its acquisition of Celgene, which had already been developing the drug.

CC-486 is an oral version of Celgenes already-marketed chemotherapy Vidaza (azacitidine), which is administered intravenously it had been a top-selling product for the company, before being hit by generic competition in the US and Europe over recent years.

Vidaza brought in over $600m a year at its peak, as a treatment for AML and myelodysplastic syndrome (MDS), but fell to only $2m last year thanks to being pretty much entirely replaced by generics.

The new formulation could allow BMS to reclaim market share by moving the drug beyond its use as a first-line induction chemotherapy thanks to its oral dosing.

We are extremely encouraged by the results of the QUAZAR AML-001 study as a part of our continuing commitment to both epigenetic research and myeloid diseases, said Samit Hariwat, chief medical officer of BMS.

We now look forward to taking the next steps to bring CC-486 to eligible AML patients in need, he added.

According to a statement issued by BMS, regulatory submissions for CC-486 are planned for the first half of 2020.

The drug is also being tested in MDS, non-Hodgkins lymphoma and other cancers, both alone and in combination with checkpoint inhibitor drugs.

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BMS' oral maintenance therapy boosts survival in AML patients - PMLiVE

Microbial Dynamics in Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation – Oncology Nurse Advisor

Researchers used a computational approach to characterize the gut microbiota of patients who had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT), and they detected impacts on microbial community composition from dietary changes and antibacterial therapies. The studys results were presented at the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, held in Orlando, Florida.

According to the studyinvestigators, the microbiota of patients often experience disruptions withallo-HSCT, and reduced microbial diversity may be associated with consequencessuch as graft-versus-host disease (GVHD).

In this study, theinvestigators performed DNA sequencing of 7930 samples from microbiomes ofpatients (N=1076) who had undergone allo-HSCT. The researchers fed thesequencing data into a clustering algorithm to evaluate patterns of diversityand composition in the microbial communities of these patients. The researchersused this algorithm to monitor changes in microbial communities withenvironmental modifiers that included antibacterial drugs and dietaryalterations.

Piperacillin-tazobactam(pip-tazo) exposure was reported to disrupt a microbial cluster (cluster 1)that had been characterized by high diversity (P <.05). This cluster,however, was not significantly impacted by cefepime and meropenem.

Pip-tazo was alsoassociated with shifts toward a cluster dominated by Streptococcus (P<.001), while shifts toward an Enterococcus-dominated clusterappeared to be encouraged by exposure to cefepime (P <.05) ormeropenem (P <.01).

Using specimens from 46patients who provided dietary details, the investigators found that cluster 1,noted for high diversity, lost stability in the presence of more protein (P<.05), while a diet with a higher fat intake was associated with increasedstability for this cluster (P <.05).

The investigators statedthat a goal of this approach to microbiota assessment, which evaluates entiremicrobial communities, is to help find treatments that enable optimal outcomesfor patients undergoing allo-HSCT.

Disclosure: Multiple authors declaredaffiliations with industry. Please refer to the original abstract for a fulllist of disclosures.


Nguyen CL, Gomes ALC, Peled JU, et al. Antibiotic exposures and dietary intakes are associated with changes in microbiota compositions in allogeneic hematopoietic stem cell transplant patients. Oral presentation at: 61st ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 597.

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Microbial Dynamics in Patients Treated With Allogeneic Hematopoietic Stem Cell Transplantation - Oncology Nurse Advisor