Archive for the ‘Stem Cells for Regenerative Medicine’ Category

The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier & Jennifer A. Doudna

Posted in Award Nominations, Cell Biology, CRISPR alternative for editing genes without cutting, CRISPR applied to Human Germ Line, CRISPR/Cas9 & Gene Editing, DNA repair, Gene Therapy & Gene Editing Development, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Interviews with Key Opinion Leaders (KOLs), Molecular Genetics & Pharmaceutical, Nobel Prize WInners, Stem Cells for Regenerative Medicine, tagged CRISPR –Cas9 system for genetic engineering, CRISPR Biology • Genome Editing • Gene Drives • DNA Repair • Model and Industrial Organisms • Technology Development • Stem Cells/Cancer • Genome-Wide Screens, CRISPR-based gene editing, CRISPR-Cas9, CRISPR/Cas and base editing, gene editing, gene editing technology platform, Jennifer Doudna, nobel leureates, Nobel Prize, Nobel Prize in Chemistry, Stanford University on October 8, 2020| Leave a Comment »

The Nobel Prize in Chemistry 2020: Emmanuelle Charpentier & Jennifer A. Doudna

Reporters: Stephen J. Williams, Ph.D. and Aviva Lev-Ari, PhD, RN

The Royal Swedish Academy of Sciences has decided to award the Nobel Prize in Chemistry 2020 to

Emmanuelle Charpentier
Max Planck Unit for the Science of Pathogens, Berlin, Germany

Jennifer A. Doudna
University of California, Berkeley, USA

“for the development of a method for genome editing”

https://www.nobelprize.org/prizes/chemistry/2020/popular-information/#:~:text=Emmanuelle%20Charpentier%20and%20Jennifer%20Doudna,microorganisms%20with%20extremely%20high%20precision.

Genetic scissors: a tool for rewriting the code of life

Emmanuelle Charpentier and Jennifer A. Doudna have discovered one of gene technology’s sharpest tools: the CRISPR/Cas9 genetic scissors. Using these, researchers can change the DNA of animals, plants and microorganisms with extremely high precision. This technology has had a revolutionary impact on the life sciences, is contributing to new cancer therapies and may make the dream of curing inherited diseases come true.

Researchers need to modify genes in cells if they are to find out about life’s inner workings. This used to be time-consuming, difficult and sometimes impossible work. Using the CRISPR/Cas9 genetic scissors, it is now possible to change the code of life over the course of a few weeks.

“There is enormous power in this genetic tool, which affects us all. It has not only revolutionised basic science, but also resulted in innovative crops and will lead to ground-breaking new medical treatments,” says Claes Gustafsson, chair of the Nobel Committee for Chemistry.

As so often in science, the discovery of these genetic scissors was unexpected. During Emmanuelle Charpentier’s studies of Streptococcus pyogenes, one of the bacteria that cause the most harm to humanity, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacteria’s ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA.

Charpentier published her discovery in 2011. The same year, she initiated a collaboration with Jennifer Doudna, an experienced biochemist with vast knowledge of RNA. Together, they succeeded in recreating the bacteria’s genetic scissors in a test tube and simplifying the scissors’ molecular components so they were easier to use.

In an epoch-making experiment, they then reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life.

Since Charpentier and Doudna discovered the CRISPR/Cas9 genetic scissors in 2012 their use has exploded. This tool has contributed to many important discoveries in basic research, and plant researchers have been able to develop crops that withstand mould, pests and drought. In medicine, clinical trials of new cancer therapies are underway, and the dream of being able to cure inherited diseases is about to come true. These genetic scissors have taken the life sciences into a new epoch and, in many ways, are bringing the greatest benefit to humankind.

Illustrations

The illustrations are free to use for non-commercial purposes. Attribute ”© Johan Jarnestad/The Royal Swedish Academy of Sciences”

Illustration: Using the genetic scissors (pdf)
Illustration: Streptococcus’ natural immune system against viruses:CRISPR/Cas9 pdf)
Illustration: CRISPR/Cas9 genetic scissors (pdf)

Important but Unseen Human Embryo Developmental Stages Mimicked in Lab

Posted in Cardiac muscle regeneration, Cell Biology, Chemical Genetics, Competition in regenerative stem cell science, Human neural progenitor cells, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation, Signaling & Cell Circuits, Skeletal muscle regeneration, Stem Cells for Regenerative Medicine, tagged gastruloids, stem cells on June 13, 2020| Leave a Comment »

Important but Unseen Human Embryo Developmental Stages Mimicked in Lab

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Scientists have created embryo-like structures that mimic a crucial yet not much known stage of human development. The structures, created from stem cells and called gastruloids, are the first to form a 3D assembly that lays out how the body will take shape. The gastruloids developed rudimentary components of a heart and nervous system, but lacked the components to form a brain and other cell types that would make them capable of becoming a viable fetus.

Human embryos take a momentous leap in their third week, when the largely homogeneous ball of cells starts to differentiate and develop specific characteristics of the body parts they will become, a process known as gastrulation. During this process, the embryo elongates and lays down a body plan with a head and tail, often called the head-to-tail axis. But scientists have never seen this process live in action. That is partly because many countries have regulations that stop embryos from being grown in the laboratory for research beyond 14 days.

Over the past years, several research groups have cultured embryonic stem-cell structures that model when cells start to differentiate. The latest model developed at the University of Cambridge, UK and their collaborators in the Netherlands, Showed for the first time what happens when the blueprint for the body’s development is laid out, around 18–21 days after conception. Genetic analysis showed that the cells formed were those that would eventually go on to form muscles in the trunk, vertebrae, heart and other organs.

If everything is done properly, the cells develop into 3D structures on their own — and then spontaneously mimic the gastrulation process. Although they display certain key features of a 21-day-old embryo, the gastruloids reach that stage after just 72 hours and survive for maximum 4 days before collapsing. Scientists will probably use the model to make structures that are even more realistic representations of early development.

The model could help scientists to understand the role of genetics and environmental factors in different disorders. The artificial structures make it possible to avoid ethical concerns about doing research on human embryos. But as the structures become more advanced and life-like, there may be ethical restrictions.

SOURCE

David Cyranoski

doi: 10.1038/d41586-020-01757-z

References for Original Study

Moris, N. et al. Nature https://doi.org/10.1038/s41586-020-2383-9 (2020)

https://www.nature.com/articles/d41586-020-01757-z?utm_source=Nature+Briefing

Other References:

https://pubmed.ncbi.nlm.nih.gov/32528178/

https://pubmed.ncbi.nlm.nih.gov/22804578/

https://pubmed.ncbi.nlm.nih.gov/24973948/

https://pubmed.ncbi.nlm.nih.gov/27419872/

https://pubmed.ncbi.nlm.nih.gov/28179190/

Read Full Post »

Human personalized autologous cell therapy for Parkinson’s Disease

Posted in Autologous Cell Therapy, Biological Engineering, Biological Networks, Biomarkers & Medical Diagnostics, Biotechnology, Cell Biology, Cell Biology, Signaling & Cell Circuits, Cell Processing System in Cell Therapy Process Development, cell-based therapy, Cerebrovascular and Neurodegenerative Diseases, Competition in regenerative stem cell science, Genomic Endocrinology, hNPCs, Innovations in Neurophysiology & Neuropsychology, Neurodegenerative Diseases, Neurohumoral Transmission, Neurological Diseases, Neuronal Circuits, Neuroscience, Parkinson's disease dyskinesia levodopa, Patient-centered Medicine, Personal Health Applications: Tech Innovations serves HealhCare, Personalized and Precision Medicine & Genomic Research, Signaling & Cell Circuits, stem cell biology and patient-specific, Stem Cells for Regenerative Medicine, tagged brain, dopamine, hiPSC, Parkinsons disease, Therapy on December 2, 2019| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Parkinson’s Disease (PD), characterized by both motor and non-motor system pathology, is a common neurodegenerative disorder affecting about 1% of the population over age 60. Its prevalence presents an increasing social burden as the population ages. Since its introduction in the 1960’s, dopamine (DA)-replacement therapy (e.g., L-DOPA) has remained the gold standard treatment. While improving PD patients’ quality of life, the effects of treatment fade with disease progression and prolonged usage of these medications often (>80%) results in side effects including dyskinesias and motor fluctuations. Since the selective degeneration of A9 mDA neurons (mDANs) in the substantia nigra (SN) is a key pathological feature of the disease and is directly associated with the cardinal motor symptoms, dopaminergic cell transplantation has been proposed as a therapeutic strategy.

Researchers showed that mammalian fibroblasts can be converted into embryonic stem cell (ESC)-like induced pluripotent stem cells (iPSCs) by introducing four transcription factors i.e., Oct4, Sox2, Klf4, and c-Myc. This was then accomplished with human somatic cells, reprogramming them into human iPSCs (hiPSCs), offering the possibility of generating patient-specific stem cells. There are several major barriers to implementation of hiPSC-based cell therapy for PD. First, probably due to the limited understanding of the reprogramming process, wide variability exists between the differentiation potential of individual hiPSC lines. Second, the safety of hiPSC-based cell therapy has yet to be fully established. In particular, since any hiPSCs that remain undifferentiated or bear sub-clonal tumorigenic mutations have neoplastic potential, it is critical to eliminate completely such cells from a therapeutic product.

In the present study the researchers established human induced pluripotent stem cell (hiPSC)-based autologous cell therapy. Researchers reported a platform of core techniques for the production of mDA progenitors as a safe and effective therapeutic product. First, by combining metabolism-regulating microRNAs with reprogramming factors, a method was developed to more efficiently generate clinical grade iPSCs, as evidenced by genomic integrity and unbiased pluripotent potential. Second, a “spotting”-based in vitro differentiation methodology was established to generate functional and healthy mDA cells in a scalable manner. Third, a chemical method was developed that safely eliminates undifferentiated cells from the final product. Dopaminergic cells thus produced can express high levels of characteristic mDA markers, produce and secrete dopamine, and exhibit electrophysiological features typical of mDA cells. Transplantation of these cells into rodent models of PD robustly restored motor dysfunction and reinnervated host brain, while showing no evidence of tumor formation or redistribution of the implanted cells.

Together these results supported the promise of these techniques to provide clinically applicable personalized autologous cell therapy for PD. It was recognized by researchers that this methodology is likely to be more costly in dollars and manpower than techniques using off-the-shelf methods and allogenic cell lines. Nevertheless, the cost for autologous cell therapy may be expected to decrease steadily with technological refinement and automation. Given the significant advantages inherent in a cell source free of ethical concerns and with the potential to obviate the need for immunosuppression, with its attendant costs and dangers, it was proposed that this platform is suitable for the successful implementation of human personalized autologous cell therapy for PD.

References:

https://www.jci.org/articles/view/130767/pdf?elqTrackId=2fd7d0edee744f9cb6d70a686d7b273b

https://www.ncbi.nlm.nih.gov/pubmed/31714896

https://www.ncbi.nlm.nih.gov/pubmed/23666606

https://www.ncbi.nlm.nih.gov/pubmed/27343168

https://www.ncbi.nlm.nih.gov/pubmed/21495962

https://www.ncbi.nlm.nih.gov/pubmed/28083784

https://www.ncbi.nlm.nih.gov/pubmed/20336395

https://www.ncbi.nlm.nih.gov/pubmed/28585381

Read Full Post »

Feeling the Heat – the Link between Inflammation and Cancer

Posted in Cytokines, Stem Cells for Regenerative Medicine, tagged Act1, Cytokines, ERK5, IL-17A, inflammation, signaling pathway, TNFR-4 on April 9, 2019| Leave a Comment »

Feeling the Heat – the Link between Inflammation and Cancer

Reporter: Irina Robu, PhD

Researchers at Lerner Research Institute led by Dr. Xiaoxia Li revealed a new signaling pathway in a subset of hair follicle stem cells that can be linked to inflammation, wound healing and tumorigenesis giving new insights into how to potential target to slow or prevent tumor initiation. However, previous research shows that uncontrolled tissue repair is usually associated with tumor formation, but there is no direct connection between them.

The scientists found that the proinflammatory cytokine, IL-17A plays a vital role in aberrant tissue repair. They showed that when IL-17A signaling is turned on, Lrig1+ stem cells expanded and their progeny translocated to other layers of the skin in reply to injury. Through a series of investigations, Dr. Li showed that the presence and physical proximity of a series of proteins sets into motion a complex signaling cascade that results in activation of ERK5 (extracellular signal regulated kinase 5), which is ultimately responsible for the expansion and migration of Lrig1+ stem cells. While many proteins including interleukin-17 receptor, epidermal growth factor receptor and Act1 are involved, tumor necrosis factor receptor associated factor 4 is the first receptor to fail, setting the entire signaling cascade in motion.

Considering that this is the first study to show that a proinflammatory cytokine can recruit a growth factor receptor to activate stem cells in support of tissue repair and tumorigenesis. This proves that tumor necrosis factor receptor associated factor 4 may be a viable therapeutic target to pursue in upcoming studies.

SOURCE

https://www.eurekalert.org/pub_releases/2011-10/lri-ccs100711.php

Read Full Post »

Immunoediting can be a constant defense in the cancer landscape

Posted in Anticancer Resistance, Apoptosis, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Breast Cancer - impalpable breast lesions, Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, Cancer Informatics, cancer metabolism, Cancer Prevention: Research & Programs, Cancer Screening, Cancer Surgery of the Heart, Cancer Vaccines: Targeting Cancer Genes for Immunotherapy, Cancer-Immune Interactions, Cell Biology, Cell Biology, Signaling & Cell Circuits, Cell death pathways, Cell Processing System in Cell Therapy Process Development, cell-based therapy, Childhood cancer, Circulating Tumor Cells (CTC), combination immunotherapies., Efficacy of Anti-Tumor T Cells, Engineering Better T Cells, Engineering Enhanced Cancer Vaccines, Funding Opportunities for Cancer Research, Human Immune System in Health and in Disease, Imaging-based Cancer Patient Management, Immune Modulatory, Immuno-Oncology & Genomics, Immunology, Immunotherapy, Infectious Disease Immunodiagnostics, Innovation in Immunology Diagnostics, Integrin-targeted Combination Immunotherapy, Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood, Liquid Biopsy: Circulating Tumor Cells in Urine and Blood, Metabolic Immuno-Oncology, Microbiome and Responses to Cancer Therapy, MicroEngineering Cell-Tissue & Systems, Modulating Macrophages in Cancer Immunotherapy, Monoclonal Immunotherapy, NK Cell-Based Cancer Immunotherapy, Pancreatic cancer, Pharmacotherapy and Cell Activity, Population Health Management, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Precision Cancer Medicine, Prostate Cancer: Monitoring vs Treatment, RNA Biology, Cancer and Therapeutics, Signaling & Cell Circuits, Single Cell Genomics, stem cell biology and patient-specific, Stem Cells for Regenerative Medicine, Synergistic Innate and Adaptive Immunotherapy, Synthetic Immunology: Hacking Immune Cells, Universal Immune Cell Therapies (uICT), Voices of Patients and Healthcare Providers, tagged Cancer, cancer vaccine, DNA, HLA, immunoediting on March 16, 2019| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

There are many considerations in the cancer immunoediting landscape of defense and regulation in the cancer hallmark biology. The cancer hallmark biology in concert with key controls of the HLA compatibility affinity mechanisms are pivotal in architecting a unique patient-centric therapeutic application. Selection of random immune products including neoantigens, antigens, antibodies and other vital immune elements creates a high level of uncertainty and risk of undesirable immune reactions. Immunoediting is a constant process. The human innate and adaptive forces can either trigger favorable or unfavorable immunoediting features. Cancer is a multi-disease entity. There are multi-factorial initiators in a certain disease process. Namely, environmental exposures, viral and / or microbiome exposure disequilibrium, direct harm to DNA, poor immune adaptability, inherent risk and an individual’s own vibration rhythm in life.

When a human single cell is crippled (Deranged DNA) with mixed up molecular behavior that is the initiator of the problem. A once normal cell now transitioned into full threatening molecular time bomb. In the modeling and creation of a tumor it all begins with the singular molecular crisis and crippling of a normal human cell. At this point it is either chop suey (mixed bit responses) or a productive defensive and regulation response and posture of the immune system. Mixed bits of normal DNA, cancer-laden DNA, circulating tumor DNA, circulating normal cells, circulating tumor cells, circulating immune defense cells, circulating immune inflammatory cells forming a moiety of normal and a moiety of mess. The challenge is to scavenge the mess and amplify the normal.

Immunoediting is a primary push-button feature that is definitely required to be hit when it comes to initiating immune defenses against cancer and an adaptation in favor of regression. As mentioned before that the tumor microenvironment is a “mixed bit” moiety, which includes elements of the immune system that can defend against circulating cancer cells and tumor growth. Personalized (Precision-Based) cancer vaccines must become the primary form of treatment in this case. Current treatment regimens in conventional therapy destroy immune defenses and regulation and create more serious complications observed in tumor progression, metastasis and survival. Commonly resistance to chemotherapeutic agents is observed. These personalized treatments will be developed in concert with cancer hallmark analytics and immunocentrics affinity and selection mapping. This mapping will demonstrate molecular pathway interface and HLA compatibility and adaptation with patientcentricity.

References:

https://www.linkedin.com/pulse/immunoediting-cancer-landscape-john-catanzaro/

https://www.cell.com/cell/fulltext/S0092-8674(16)31609-9

https://www.researchgate.net/publication/309432057_Circulating_tumor_cell_clusters_What_we_know_and_what_we_expect_Review

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190561/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840207/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593672/

https://www.frontiersin.org/articles/10.3389/fimmu.2018.00414/full

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5593672/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190561/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4388310/

https://www.linkedin.com/pulse/cancer-hallmark-analytics-omics-data-pathway-studio-review-catanzaro/

Read Full Post »

Functioning Human Neural Networks Grown in 3D from Stem Cells

Posted in 3D Plotting Scaffolds, 3D Printing for Medical Application, BioPrinting in Regenerative Medicine, Stem Cells for Regenerative Medicine, Tissue Engineering, Tissue Engineering and Regenerative Medicine, tagged human induced pluripotent stem cells, neural tissue, neurons, Organoids, silk-collagen scaffolds on January 13, 2019| Leave a Comment »

Functioning Human Neural Networks Grown in 3-D from Stem Cells

Reporter: Irina Robu, PhD

Researchers at Tuffs University developed three-dimensional human tissue model that mimics structural and functional features of the brain and were able to demonstrate sustained neural activity over several months. The 3D brain tissue models were the result of a collaborative effort between researchers from Tufts University School of Engineering, Tufts University School of Medicine, the Sackler School of Graduate Biomedical Sciences at Tufts, and the Jackson Laboratory.

These tissue models have the ability to populate a 3D matrix of silk protein and collagen with cells from patients with Parkinson’s disease, Alzheimer’s disease and the ability to

explore cell interactions,
disease progression and
response to treatment.

The 3D brain tissue models overcome a crucial challenge of previous models which is the availability of human source neurons due to the fact that neurological tissues are rarely removed from

healthy patients, and are usually available
post-mortem from diseased patients.

The 3D tissue models are populated with human induced pluripotent stem cells (iPSCs) that can be derived from several sources, including patient skin. The iPSCs are generated by turning back the clock on cell development to their embryonic-like precursors. They can then be dialed forward again to any cell type, including neurons. The porous structure of the 3D tissue cultures labeled in the research delivers sufficient oxygenation, access for nutrients and measurement of cellular properties. A clear window in the center of each 3D matrix allows researchers to visualize the

growth,
organization and
behavior of individual cells.

According to David L. Kaplan, “the silk-collagen scaffolds provide the right environment to produce cells with the genetic signatures and electrical signaling found in native neuronal tissues”. Compared to growing and culturing cells in two dimensions, the three-dimensional matrix yields a knowingly extra complete mix of cells found in neural tissue, with the appropriate morphology and expression of receptors and neurotransmitters. Other researchers have used iPSCs to create brain-like organoids, but can still make it difficult figuring out what individual cells are doing in real time. Likewise, cells in the center of the organoids may not obtain enough oxygen or nutrients to function in a native state.

However, the researchers can see a great advantage of the 3D tissue models with advanced imaging techniques, and the addition of cell types such as microglia and endothelial cells,to create a more complete model of the brain environment and the complex interactions that are involved in

signaling,
learning and plasticity, and
degeneration.

SOURCE

https://www.rdmag.com/news/2018/10/scientists-grow-functioning-human-neural-networks-3d-stem-cells

Read Full Post »

CALD Gene Therapy Granted “Breakthrough Therapy Designation”

Posted in Cancer - General, Gene Therapy & Gene Editing Development, Genetics & Pharmaceutical, Stem Cells for Regenerative Medicine, Tissue Engineering and Regenerative Medicine, tagged ABCD1 gene, adrenoleukodystrophy, ALD, allogenic, hematopietic stem cells, Lenti-D on December 28, 2018| Leave a Comment »

CALD Gene Therapy Granted “Breakthrough Therapy Designation”

Reporter: Irina Robu, PhD

Bluebird Bio’s Lenti D has been granted as “breakthrough therapy designation” by FDA for the treatment of patients with cerebral adrenoleukodystrophy (CALD), or Lorenzo’s Oil disease due to optimistic data from current ongoing Phase 2/3 study. This therapy contains using patient’s own immature bone marrow cells and modifying them to include a functional copy of ABCD1 gene which permits the expression of functional ALD, the deficient protein in the patient population.

In addition, the data indicated that the safety profile of Lenti-D remains consistent with myeloablative chemotherapy and no graft versus host disease or treatment related mortality were reported. Initial findings from the ongoing Starbeam Study (ALD-102) assessing the investigational gene therapy in boys with CALD aged 17 years or younger who do not have a matched sibling donor were published in the New England Journal of Medicine in October 2017 and indicated that the drug hit its main effectiveness endpoint. In the study, 88% (n=15) of patients infused with Lenti-D remained alive and free of major functional disabilities at 2 years post-treatment.

According to Mohammed Asmal, Vice President, Clinical Development at bluebird bio “The mechanism by which this would work is very much like how stem cell therapy transplantation is able to correct the disease. The theory was certainly there, it just relied on someone, essentially, being willing to develop the vector and then try it on patients who did not have any other feasible options for transplant, and who had poor predicted outcomes for transplant survival.”

Currently, the only available therapeutic option for patients with CALD is allogeneic hematopoietic stem cell transplant (HSCT). Whereas clinical benefit has been reported if made early during CALD progression, possible complications of allogeneic HSCT can be fatal. According to David Davison, chief medical officer at Bluebird Bio “FDA’s Breakthrough Therapy designation for Lenti-D brings new hope to the patients and families affected by this devastating disease”.

SOURCE

https://patientworthy.com/2018/05/29/gene-therapy-ald-breakthrough-therapy-fda/

Read Full Post »

NHLBI decision to halt Heart Stem-Cell Study (CONCERT-HF trial) due to concerns about Anversa’s Animal Studies, not due to any Data generated by the Clinical trial itself, no compromised patient safety by trial

Posted in FDA Regulatory Affairs, Heart Failure (HF), Personalized and Precision Medicine & Genomic Research, Regenerative Biology and Medicine, Stem Cells for Regenerative Medicine on October 31, 2018| Leave a Comment »

NHLBI decision to halt Heart Stem-Cell Study (CONCERT-HF trial) due to concerns about Anversa’s Animal Studies, not due to any Data generated by the Clinical trial itself, no compromised patient safety by trial

Reporter: Aviva Lev-Ari, PhD, RN

The National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, is pausing the CONCERT-HF trial external link, which involves patients with chronic heart failure. Recent calls for the retraction of journal articles in related fields of cell therapy research have raised concerns about the scientific foundations of this trial. While none of the articles in question derive from the CONCERT-HF trial itself, the NHLBI convened CONCERT-HF’s Data and Safety Monitoring Board (DSMB) out of an abundance of caution to ensure the study continues to meet the highest standards for participant safety and scientific integrity. Informed by the DSMB recommendations of October 25, 2018, the NHLBI is pausing the trial. While the DSMB did not have any participant safety concerns, this pause enables the DSMB to complete its review.

The safety of all clinical trial participants is paramount to NHLBI. NHLBI will honor its commitment to CONCERT-HF participants and continue the follow-up protocol during this pause for all participants who have already been treated in the study. Participants are being notified of the status of the trial and how to request additional information.

The CONCERT-HF trial seeks to determine whether c-kit+ cells, either alone or in combination with mesenchymal stem cells derived from the bone marrow, are safe and benefit patients with chronic heart failure, who have very limited treatment options. Despite significant medical and surgical advances, patients with heart failure continue to experience a low quality of life and about half of them will die within five years of receiving a diagnosis.

The scientific basis of CONCERT-HF is supported by a body of evidence in several preclinical models in a number of studies in a variety of laboratories and was reviewed by a Protocol Review Committee (PRC) independent of the trial. The cell therapies that CONCERT-HF is testing are under an investigational new drug (IND) designation which is overseen by the U.S. Food and Drug Administration (FDA). The cells are produced by an accredited laboratory independent of the clinical sites. In addition, as part of standard oversight of clinical trials, the DSMB routinely reviews and monitors CONCERT-HF to ensure participant safety and that the study continues to ask compelling scientific questions with implications for patient care.

The DSMB’s review will be conducted as expeditiously as possible and will inform NHLBI’s future actions that will ensure the highest standards of participant safety and scientific integrity.

SOURCE

https://www.nhlbi.nih.gov/news/2018/statement-nhlbi-decision-pause-concert-hf-trial

References

Quaini, F. et al. N. Engl. J. Med. 346, 5–15 (2002).

Murry, C. E. et al. Nature 428, 664–668 (2004).

Balsam, L. B. Nature 428, 668–673 (2004).

Nygren, J. M. et al. Nature Med. 10, 494–501 (2004).

Download references

RELATED ARTICLES

SUBJECTS

SOURCE

Read Full Post »

LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

Posted in cell-based therapy, Competition in regenerative stem cell science, Patient-centered Medicine, Personalized and Precision Medicine & Genomic Research, stem cell biology and patient-specific, Stem Cells for Regenerative Medicine on October 9, 2018| Leave a Comment »

LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

REAL TIME Reporter: Aviva Lev-Ari, PhD, RN

AWARD LECTURE

Tue., Oct. 9, 2018
4:00 PM
Shapiro Campus Center Theater
Brandeis University

ROSENSTIEL BASIC MEDICAL SCIENCES RESEARCH CENTER > GABBAY AWARD > CURRENT WINNER

CURRENT WINNER

LORENZ STUDER

MACARTHUR FELLOWS PROGRAM

Lorenz Studer

Stem Cell Biologist | Class of 2015

Pioneering a new method for large-scale generation of dopaminergic neurons that could provide one of the first treatments for Parkinson’s disease and prove the broader feasibility of stem cell–based therapies for other neurological disorders.

https://www.macfound.org/fellows/947/

118 publications on PubMed

https://www.ncbi.nlm.nih.gov/pubmed/?term=LORENZ+STUDER

PRESIDING

Dagmar Ringe Professor of Biochemistry, Chemistry and Rosenstiel Basic Medical Sciences Research Center

WELCOME

Lisa Lynch Provost and Maurice B. Hexter Professor of Social and Economic Policy Brandeis University

RESPONSE Lorenz Studer, MD Director, Center for Stem Cell Biology Memorial Sloan Kettering Cancer Center Member, Developmental Biology Program Memorial Sloan Kettering Cancer Center

Fully defined protocol for all ectodermal lineage

Nervous system: Forebrain, Midbrain, Spinal cord:
CNS lineage to PNS Lineage
Excitatory cortical neurons
cortical interneurons Astrocytes
microglia
Age-reset disease – late-onset during reprogramming – Is age reversible?
Loss of age-related markers
iPSC-derived cells yield stage cell upon differentiation
In vitro differentiation techniques: 2D Directed Differentiation 3D- Organoids
Graded MORPHOGEN SIGNALING
DOXYCYLINE: ISHH-ORGANIZER – 5 discrete forebrain regions
Building Human brain cells in 2D and in 3D
Organized cells –>>> directed organoids –>> Organized Organoids
Parkinson, 1817 – Essay on Shaky Palsy (Niagrostaterial pathway)
Genetics and related dysfunction: affecting PD
Charckot, 1889
PD – new approach following drugs and deep brain stimulation failure in advanced disease: Fetal tissue transplant trials: Fetal Grafting
graft-induced dyskinesia
Long term, 15 years positive effects
Stem-cell-based regenerative therapy could transform PD therapy
1995 Fetal DA neuron grafting for PD in Switzerland
1998 – midbrain stem cell derived DA neuron
200-2003 – Stem cell in brain implantation in WashDC
2011 – Behavioral assays that are restored in mice
Optogenetics: manipulating – Light on the brain – control animal’s neurons
MOA of Graft function
Dopamine neurons – Stratium area of the human brain
From bench to bedside – WNT boost enhances EN1 expression
Neuron melanin induction
Manufacturing and QA testing: GMP – Off the shelf Allogenic Product
1,000 human dose equivalents
cryopreserve
MSK-DA01 is highly enriched for mDA neuron precursors without detectable hESC Contaminants
FDA feedback and final steps to IND – PRE-IND MEETING: 2014, 2016
GLP STUDIES:
TUMORIGENICITY, BIODISTRIBUTION AND TOXISITY
HISTOLOGY OF FINAL PRODUCT
CLINICAL TRIAL DESIGN – STEM-PD – MSK and Weill Cornell Medicine
HLA expression is absent in edited iPSC with expression of HLA-E to block NK clearance
FUTURE: CRISPR
ATLaS-PD – assessing the longitudinal Symptoms/signs to moderate of severe stage
Development of a new PD therapy from Pluripotent Stem Cells
BlueRock Therapeutics – MSK-PD – Start up – $240Million funding
Stem cell based dopamine therapy for PD
Immunosuppression for 12 months
defined levodopa response > 45% improvement
Conclusions
Cell banks for clinical trials
NY state Stem cell science consortia

http://www.brandeis.edu/rosenstiel/images/pdfs/gabbay21program.pdf

Read Full Post »

Stem Cells Used as Delivery Truck for Brain Cancer Drugs

Posted in Biological Engineering, Cancer - General, Childhood cancer, Drug Carrier Design, Drug Delivery Platform Technology, Regenerative Biology and Medicine, Stem Cells for Regenerative Medicine, tagged Cell therapy, cytotoxic agent, genetic engineering, medulloblastoma, skin cells on September 2, 2018| Leave a Comment »

Stem Cells Used as Delivery Truck for Brain Cancer Drugs

Reporter: Irina Robu, PhD

Medulloblastoma, common brain cancer in children has been very difficult to treat therapeutically with traditional interventions which relies on surgical techniques to remove the bulk of the cancerous tissue. The researchers seen the need for novel treatments of medulloblastomas that have recurred, as well as for treatments that are less toxic overall. For this reason, data from University of North Carolina (UNC) Lineberger Comprehensive Cancer Center and Eshelman School of Pharmacy published a study in PLOS named “Intra-cavity stem cell therapy inhibits tumor progression in a novel murine model of medulloblastoma surgical resection”, validates how cancer-hunting stem cells can track down and deliver a drug to terminate medulloblastoma cells hiding after surgery.

The technology in the research is an extension of a discovery that won researchers a Nobel Prize in 2012 and showed they could transform skin cells into stem cells. The research team started by reprogramming skin cells into stem cells and genetically engineered them to manufacture a substance that becomes toxic to other cells when exposed to another drug. Inserting the drug carries the stem cells into the brain of laboratory models after surgery decreased the size of tumors by 15 times and extended median survival in mice by 133%.

In this study, the scientists indicated they could shrink tumors in murine models of medulloblastoma, hence extending the rodents life. The approach holds promise for reducing side effects and helping more children with medulloblastoma. Amazingly the researchers also developed a laboratory model of medulloblastoma that allowed them to simulate the way standard care is currently delivered—surgery followed by drug therapy. Using this model, they discovered that after surgically removing a tumor, the cancer cells that remained grew faster.

According to the study investigator, Shawn Hingtgen, PhD, the cells are like a FedEx truck that will deliver cytotoxic agents directly into the tumor to a particular location. In earlier studies, Dr. Hingtgen and his colleagues showed that they could flip skin cells into stem cells that hunt and transport cancer-killing drugs to glioblastoma, the deadliest malignant brain tumor in adults.

Medulloblastoma is cancer that happens mostly in kids between ages of three and eight, and while current therapy has changed survival pretty dramatically, it can still be pretty toxic. The ability to use a patient’s own cells to target the tumor directly would be “the holy grail” of therapy, the investigators trust it could hold capacity for other rare, and sometimes fatal, brain cancer types that occur in children as well.

Source

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0198596