The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen By Benjamin Mateus 10 October 2019

In the course of a lifetime, the human heart will beat more than three billion times. We will have taken more than 670 million breaths before we reach the end of our lives. Yet, these critical events remain unconscious and imperceptible in everyday life, unless we exert ourselves, such as running up several flights of stairs. We quickly tire, stop to take deep breaths and become flushed.

With the deepening comprehension by medical science of how our bodies work, we have come to better understand the fundamental importance of oxygen to life. Every living organism relies on it in one form or another. However, how cells and tissues can monitor and respond to oxygen levels remained difficult to elucidate. It has only been late in the 20th century with advances in cellular biology and scientific instrumentation that these processes have finally been explained.

On Monday, the 2019 Nobel Prize in Physiology or Medicine was awarded jointly to three individuals: William G. Kaelin, Jr., Sir Peter J. Ratcliffe, and Gregg L. Semenza. Specifically, their discoveries helped elucidate the mechanisms for lifes most basic physiologic processes.

They were able to discover how oxygen levels directly affect cellular metabolism, which ultimately controls physiological functions. More importantly, their findings have significant implications for the treatments of conditions as varied as chronic low blood counts, kidney disease, patients with heart attacks or stroke and cancers. One of the hallmarks of cancer is its ability to generate new blood vessels to help sustain its growth. It also uses these oxygen cellular mechanisms to survive in low oxygen environments.

Dr. William G. Kaelin Jr. is a professor of medicine at Harvard University and the Dana-Farber Cancer Institute. The main focus of his work is on studying how mutations in what are called tumor suppressor genes lead to cancer development. Tumor suppressor genes are special segments of the DNA whose function is to check the integrity of the DNA before allowing a copy of itself to be made and undergo cell division, which prevents cells from propagating errors. Cellular mechanisms are then recruited to fix these errors or drive the cell to destroy itself if the damage is too severe or irreparable.

His interest in a rare genetic disorder called Von Hippel-Lindau disease (VHL) led him to discover that cancer cells that lacked the VHL gene expressed abnormally high levels of hypoxia-regulated genes. The protein called the Hypoxia-Inducible Factor (HIF) complex was first discovered in 1995 by Gregg L. Semenza, a co-recipient of the Nobel Prize. This complex is nearly ubiquitous to all oxygen-breathing species.

The function of the HIF complex in a condition of low oxygen concentration is to keep cells from dividing and growing, placing them in a state of rest. However, it also signals the formation of blood vessels, which is important in wound healing as well as promoting the growth of blood vessels in developing embryos. In cancer cells, the HIF complex helps stimulate a process called angiogenesis, the formation of new blood vessels, which allows the cancer cells to access nutrition and process their metabolic waste, aiding in their growth. When the VHL gene is reintroduced back into the cancer cells, the activity of the hypoxia-regulated genes returns to normal.

Dr. Gregg L. Semenza is the founding director of the vascular program at the Johns Hopkins Institute for Cell Engineering. He completed his residency in pediatrics at Duke University Hospital and followed this with a postdoctoral fellowship at Johns Hopkins. His research in biologic adaptations to low oxygen levels led him to study how the production of erythropoietin (EPO) was controlled by oxygen. EPO is a hormone secreted by our kidneys in response to anemia. The secretion of EPO signals our bone marrow to produce more red blood cells.

His cellular and mouse model studies identified a specific DNA segment located next to the EPO gene that seemed to mediate the production of EPO under conditions of low oxygen concentration. He called this DNA segment HIF.

Sir Peter J. Ratcliffe, a physician and scientist, trained as a nephrologist, was head of the Nuffield Department of Clinical Medicine at the University of Oxford until 2016, when he became Clinical Research Director at the Francis Crick Institute. Through his research on the cellular mechanisms of EPO and its interaction between the kidneys and red cell production, he found that these mechanisms for cellular detection of hypoxia, a state of low oxygen concentration, were also present in several other organs such as the spleen and brain. Virtually all tissues could sense oxygen in their micro-environment, and they could be modified to give them oxygen-sensing capabilities.

Dr. Kaelins findings had shown that the protein made by the VHL gene was somehow involved in controlling the response to low oxygen concentrations. Dr. Ratcliffe and his group made the connection through their discovery that the protein made by the VHL gene physically interacts with HIF complex, marking it for degradation at normal oxygen levels.

In 2001, both groups published similar findings that demonstrated cells under normal oxygen levels will attach a small molecular tag to the HIF complex that allows the VHL protein to recognize and bind HIF, marking it for degradation by enzymes. If the oxygen concentration is low, the HIF complex is protected from destruction. It begins to accumulate in the nucleus where it binds to a specific section of the DNA called hypoxia-regulating genes, which sets into motion the necessary mechanisms to respond to the low oxygen concentration.

The ability to sense oxygen plays a vital role in health and various disease states. Patients who suffer from chronic kidney failure also suffer from severe anemia because their ability to produce EPO is limited. This hormone is necessary for the stem cells in our bone marrow to produce red blood cells. Understanding how cancer cells utilize oxygen-sensing mechanisms has led to a variety of treatments that targets these pathways. The ability to elucidate these mechanisms offers insight into directions scientists and researchers can take to design or create novel treatments.

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The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen - World Socialist Web Site

Bone Marrow Stem Cells Comments Off on The 2019 Nobel Prize in Medicine awarded for research in cellular responses to oxygen – World Socialist Web Site | October 12th, 2019

PENNY Lancaster was reduced to tears as she handed five-year-old Ronnie Musselwhite the Young Hero gong at The Suns Who Cares Wins health awards last night.

Spurs fan Ronnie bravely offered to give his older sister Ebonie a bone marrow transplant last year.

Eight-year-old Ebonie had leukaemia and it was her only hope.

Mum Christine Jenkins, 40, said: Ronnies stem cells worked perfectly. They did what they were supposed to do but the leukaemia came back somewhere new.

Ebonie, of Crawley, West Sussex, nominated her younger brother before her death in June.

Rod Stewarts partner Penny chatted with Ronnie about his love of football and Spurs.

She said: To say I am humbled to be here is an understatement. Sometimes you think life has turned a corner on you, but then someone else turns up to give you some inspiration.

"The courage this little man has shown is absolutely incredible. Hes only five years old, hes lost a sister.

"He was incredibly shy to stand up in front of everyone to collect his award, but he again was so brave.

Christine said: We want Ronnie to know that what he did still worked, was still brave, even though he lost his sister.

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PM Boris Johnson was also at the awards held at The Suns London HQ near The Shard and paid tribute to our NHS heroes.

He presented an award to a pair of quick-thinking hospital porters who saved the life of a seven-week-old baby boy.

Nick Evans, 48, and Ruth Lowe, 47, sprang into action after Logan Clifford stopped breathing.

His parents, Sarah and Mike were visiting a relative at the Princess Royal Hospital in Telford, Shrops, when they noticed Logans lips had turned blue.

Sarahs screams alerted Ruth, who shouted for Nick. He grabbed Logan and performed CPR as he ran half a mile down the corridor to A&E.

Nick continued CPR until the resuscitation team took over and the porters stayed by Logans parents side until they knew he was going to be OK. Sarah, 30, has called the two porters my heroes.

As he handed the pair the Ultimate Lifesaver trophy, the PM said: The NHS is revered around the world, and in no small part due to the heroes working in it every day.

He added: My experience of the NHS is like everybody else in the NHS - one of admiration and love.

"It is the most extraordinary institution in the world. If our country was an omelette then the NHS is the egg white that holds the great British cake together.

Virgin Radio DJ Chris Evans presented the Best Nurse gong to Liz Monaghan, 53. She set up the widely praised Purple Rose initiative, which aims to improve the care for patients and their loved ones in the last days of their life.

Liz, who works at the Florence Nightingale Hospice, based at the Stoke Mandeville Hospital in Aylesbury, Bucks, said: Im a little embarrassed to have won. Im a small part of a big team.

DJ Chris said: Youve got to prepare yourself for nights like this because otherwise they hit you like an express train.

Who Cares Wins Awards: The winners

BEST HEALTH CHARITY

Winner: Matt Hampson Foundation

Former English rugby union player Matt Hampson set up a charity to help others after being left paralysed in a scrum in 2005.

Other nominees: Superhero Foundation and Team Domenica

BEST NEONATAL SPECIALIST

Winner: Professor Kypros Nicolaides

Professor Nicolaides performed pioneering keyhole surgeon on Sherrie Sharps unborn son Jaxon. By extraordinary coincidence, as a young surgeon, he also operated on Sherries mother when she was in the womb.

Other nominees: Dr Vesna Pavasovic and Professor Massimo Caputo

UNSUNG HERO

Winner: Therapeutic Care Volunteers at South Tees NHS Foundation Trust

30 therapeutic care volunteers, who all have a learning or physical disability, give up their time to support patients with spinal injuries at The James Cook University Hospital in Middlesbrough. They include Ify Nwokoro.

Other nominees: Ben Slack and Rob Allen

GROUNDBREAKING PIONEER

Winner: Guys and St Thomas London Auditory Brainstem Implant (ABI) Service

Leia Armitage, eight, was born with a rare form of deafness and was never expected to speak. But she now can thanks to pioneering brain surgery and speech therapy carried out by Guys and St Thomas London Auditory Brainstem Implant (ABI) Service.

Other nominees: Dr Helen Spencer and Girish Vajramani

BEST DOCTOR

Winner: Dr Matthew Boulter

Dr Boulter served in Afghanistan, teaches wild trauma to army medics and his surgery became the first in Cornwall to be given veteran friendly accreditation.

Other nominees: Margaret France and Dr Bijay Sinha

BEST MIDWIFE

Winner: Jane Parke

Jane helped deliver the youngest surviving twin boys in Britain when they were born at 22 weeks last year. She flew 190 miles with their mum Jennie Powell to a specialist neonatal unit.

Other nominees: Charlotte Day and Nagmeh Teymourian

ULTIMATE LIFESAVER

Winner: Ruth Lowe and Nick Evans

Porters Ruth and Nick saved the life of Sarah and Mike Cliffords seven-week-old baby Logan. He stopped breathing as they walked through the main entrance of The Princess Royal Hospital in Telford to visit a sick relative.

Other nominees: Dr Mark Forrest and Mike Merrett

BEST NURSE

Winner: Liz Monaghan

Liz is the Matron of the Florence Nightingale Hospice in Aylesbury, Bucks, and came up with the idea for the widely praised Purple Rose initiative to improve the care for patients in the last days of their lives.

Other nominees: Margaret Ballard and Carlton DeCosta

MENTAL HEALTH HERO

Winner: Ben West

Ben lost his brother Sam, 15, to suicide last year and since his death, has campaigned tirelessly to raise awareness for mental health.

Other nominees: Beth Gregan and Catherine Benfield

YOUNG HERO

Winner: Ronnie Musselwhite

Ronnie offered to help his sister Ebonie by giving her a bone marrow transplant when she was diagnosed with a rare form of leukaemia. Ebonie nominated her brother for his bravery before she died in June.

Other nominees: Bella Field and Kaitlyn Wright

I only walked ten metres into the room tonight and I already nearly burst into tears three times.

TV star Christine Lampard gave the Best Neonatal Specialist award to Prof Kypros Nicolaides, 66.

He was nominated by Sherrie Sharp, 29, of Horsham, West Sussex, for saving the life of her unborn baby son and her own.

After scans revealed Jaxson had spina bifida, Sherrie was offered a termination. But she contacted Prof Nicolaides, a surgeon at Kings College Hospital, London.

He had saved her life 30 years earlier when she developed a rare blood disorder in her mums womb.

He agreed to perform ground-breaking surgery on Jaxson while he was in Sherries womb.

Prof Nicolaides said: I was delighted to be able to help. Sherrie said: He has saved so many generations of my family. Hes our guardian angel.

The Who Cares Wins Awards were set up in 2017 by The Sun to honour the nations heroic doctors, nurses, midwives, other NHS staff and volunteers.

The Duchess of York presented an award to the parents of Natasha Ednan-Laperouse, 15, who died of an allergic reaction to a sandwich from Pret.

The duchess said: Can I just say to The Sun, I think youre incredible. Every minute Im sitting there and thinking Im so lucky. The NHS, The Sun and all of you, this is what makes Britain so great.

Lorraine Kelly, who presented the awards, said: Earlier on this year my dad was very sick and we honestly thought we were going to lose him.

"It was really difficult and it was only because of the efforts of the NHS hes still here. Its fantastic.

Who Cares Wins Awards: The winners

BEST HEALTH CHARITY

Nominees: Superhero Foundation

Team Domenica

Winner: Matt Hampson Foundation

Former English rugby union player Matt Hampson set up a charity to help others after being left paralysed in a scrum in 2005.

BEST NEONATAL SPECIALIST

Nominees: Dr Vesna Pavasovic

Professor Massimo Caputo

Winner: Professor Kypros Nicolaides

Professor Nicolaides performed pioneering keyhole surgeon on Sherrie Sharps unborn son Jaxon. By extraordinary coincidence, as a young surgeon, he also operated on Sherries mother when she was in the womb.

UNSUNG HERO

Nominees: Ben Slack

Rob Allen

Winner: Therapeutic Care Volunteers at South Tees NHS Foundation Trust

30 therapeutic care volunteers, who all have a learning or physical disability, give up their time to support patients with spinal injuries at The James Cook University Hospital in Middlesbrough. They include Ify Nwokoro.

GROUNDBREAKING PIONEER

Nominees: Dr Helen Spencer

Girish Vajramani

Winner: Guys and St Thomas London Auditory Brainstem Implant (ABI) Service

Leia Armitage, eight, was born with a rare form of deafness and was never expected to speak. But she now can thanks to pioneering brain surgery and speech therapy carried out by Guys and St Thomas London Auditory Brainstem Implant (ABI) Service.

BEST DOCTOR

Nominees: Margaret France

Dr Bijay Sinha

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Penny Lancaster is reduced to tears as she gives bone marrow donor Ronnie Musselwhite, 5, The Suns Young H - The Sun

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NEW YORK, Oct. 07, 2019 (GLOBE NEWSWIRE) -- BrainStorm Cell Therapeutics Inc.(NASDAQ: BCLI), a leading developer of adult stem cell therapeutics for neurodegenerative diseases, today announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance for BrainStorm's new US Patent Application, number: 15/113,105, titled: Method of Qualifying Cells'.

The allowed claims cover a pharmaceutical composition for MSC-NTF cells secreting neurotrophic factors (NurOwn) comprising a culture medium as a carrier and an isolated population of differentiated bone marrow-derived MSCs that secrete neurotrophic factors.

Patent families protecting NurOwn have previously issued in the United States, Japan, Europe, Hong-Kong and Israel.

"This allowance further expands the patent protection of the NurOwn Cellular Therapeutic Technology Platform and enables us to accelerate clinical development for new neurodegenerative indications, commented BrainStorm President and CEO,Chaim Lebovits.

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm is currently conducting a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received U.S. FDA acceptance to initiate a Phase 2 open-label multicenter trial in progressive MS and enrollment began in March 2019.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) in ALS. BrainStorm is currently enrolling a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in the U.S., supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive Multiple Sclerosis. The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) started enrollment in March 2019. For more information, visit the company's website at http://www.brainstorm-cell.com

Safe-Harbor Statements

Statements in this announcement other than historical data and information constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, risks associated with BrainStorm's limited operating history, history of losses; minimal working capital, dependence on its license to Ramot's technology; ability to adequately protect the technology; dependence on key executives and on its scientific consultants; ability to obtain required regulatory approvals; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

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BrainStorm Announces Notice of US Patent Allowance for NurOwn Cellular Therapeutic Technology Platform - Yahoo Finance

Bone Marrow Stem Cells Comments Off on BrainStorm Announces Notice of US Patent Allowance for NurOwn Cellular Therapeutic Technology Platform – Yahoo Finance | October 9th, 2019

A newly designed viral vector the vehicle that delivers a gene therapyto a patients cells for use insickle cell anemia is more efficient than earlier vectors at introducing healthy copies of genes into stem cells and can be produced in greater amounts, studies in animal models show.

The study Development of a forward-orientated therapeutic lentiviral vector for hemoglobin disorders was published in the journal Nature Communications.

Hemoglobin is the protein in red blood cells that binds oxygen, allowing oxygen to be transported around the body. Mutations in the HBBgene, which encodes a component of hemoglobin, causessickle cell.

Gene therapies involve either altering the mutated gene or introducing a healthy version of that gene to the body. Still under development for sickle cell, an estimated 27 patients have undergone experimental gene therapy. One strategy involves removing hematopoietic stem cells (which function to produce blood cells) from a patients bone marrow. A healthy copy of the HBB gene is then introduced into the cells using a modified, harmless virus known as a viral vector. The cells are then transplanted back into the patient where they will produce healthy red blood cells.

Traditionally, viral vectors for sickle cell have been designed in a way known as reverse structural orientation. This means that the HBB gene is translated or read from right to left, like reading an English sentence backwards. The reverse structural orientation design ensures that a key section of the gene (known as intron 2), which is necessary for the production of high levels of the HBB gene, is retained during viral vector preparation.

However, this design makes preparing the viral vectors more difficult, and decreases the efficiency of introducing the gene into the stem cells.

Researchersat the National Institutes of Healthdesigned a new viral vector, one in which the HBB gene is forward orientated and read from left to right. Genes essential for the virus were inserted into intron 2, meaning that only vectors that retained intron 2 would be produced (a type of positive selection).

Our new vector is an important breakthrough in the field of gene therapy for sickle cell disease, John Tisdale, MD, chief of the Cellular and Molecular Therapeutic Branch at the National Heart, Lung, and Blood Institute (NHLBI) and the studys senior author, said in a press release.

Its the new kid on the block and represents a substantial improvement in our ability to produce high capacity, high efficiency vectors for treating this devastating disorder, he added.

The researchers compared the new vectors to traditional reverse-orientated vectors in mouse and monkey models. The new vectors were four to 10 times more efficient at introducing the healthy HBBgene into the stem cells, and could carry up to six times more HBB genes compared to the conventional vectors.

Furthermore, the new vectors remained incorporated into the cells of monkeys up to four years after a transplant. These vectors could also be produced in greater amounts, which may lessen the time and costs required for large-scale vector production.

The researchers hope that these characteristics will make gene therapy for sickle cell disease more effective and increase its use. The new vector design still needs to be tested in clinical trials in patients.

Our lab has been working on improving beta-globin vectors for almost a decade and finally decided to try something radically different and it worked, Tisdale said.

These findings bring us closer to a curative gene therapy approach for hemoglobin disorders, he added.

Patricia holds her Ph.D. in Cell Biology from University Nova de Lisboa, and has served as an author on several research projects and fellowships, as well as major grant applications for European Agencies. She also served as a PhD student research assistant in the Laboratory of Doctor David A. Fidock, Department of Microbiology & Immunology, Columbia University, New York.

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Margarida graduated with a BS in Health Sciences from the University of Lisbon and a MSc in Biotechnology from Instituto Superior Tcnico (IST-UL). She worked as a molecular biologist research associate at a Cambridge UK-based biotech company that discovers and develops therapeutic, fully human monoclonal antibodies.

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New Viral Vector for Sickle Cell Gene Therapy Likely to Be More Effective, NIH Study Says - Sickle Cell Anemia News

Bone Marrow Stem Cells Comments Off on New Viral Vector for Sickle Cell Gene Therapy Likely to Be More Effective, NIH Study Says – Sickle Cell Anemia News | October 9th, 2019

DORVAL, QC, Oct. 9, 2019 /CNW/ - Novartis Pharmaceuticals Canada Inc. is pleased to announce that sites in Quebec have been certified in accordance with applicable requirements to treat eligible patients with Kymriah (tisagenlecleucel), the first chimeric antigen receptor T cell (CAR-T) therapy that received regulatory approval in Canada. Patients with relapsed/refractory (r/r) pediatric and young adult B-cell acute lymphoblastic leukemia (ALL) and adult r/r diffuse large B-cell lymphoma (DLBCL) may be eligible to be treated with Kymriah at one of the initially certified Canadian treatment sites. This news coincides with the Quebec government announcement that Kymriah is now reimbursed for eligible patients under the Rgie de l'assurance maladie du Qubec (RAMQ)ii.

Eligible patients in Quebec are now able to access Kymriah from the Centre hospitalier universitaire (CHU) Sainte-Justine and Maisonneuve-Rosemont Hospital (HMR) in Montreal.

"Novartis feels it is important to acknowledge the collaborative effort by all stakeholders involved to ensure Canadians have access to the first approved CAR-T therapy for patients with B-cell ALL and DLBCL who historically have poor outcomes. With treatment centers certified in Quebec, this allows patients with these two life-threatening cancers the opportunity to be treated with CAR-T therapy," said Daniel Hbert, Medical Director, Novartis Pharmaceuticals Canada Inc. "Novartis is committed to bringing additional qualified treatment centers from other parts of the country into the network to give Canadians the opportunity to be treated closer to home."

Due to the sophisticated and individualized nature of Kymriah, treatment sites that are part of the network are required to be FACT-accredited (Foundation for the Accreditation of Cellular Therapy), qualified to perform intravenous infusion of stem cells collected from the bone marrow of a donor, also referred to as allogeneic hematopoietic stem cell transplantation (alloSCT) and have experience with cell therapies, leukemia and lymphoma to facilitate safe and seamless delivery of Kymriah to eligible patients.

"We are thrilled with this news because we will now be able to treat patients at our institution with the knowledge that their therapy will be publicly funded. We see this as a significant step forward. The young patients we see who have refractory or relapsed B-cell ALL are desperately in need of a new treatment option. Kymriah brings hope to patients who are literally in a fight for their life." said Dr. Henrique Bittencourt, hematologist at the CHU Sainte-Justine in Montreal and Associate Professor, Department of Pediatrics, Universit de Montral.

"The expertise at HMR has raised the profile of our organization, which is a major Quebec, Canadian and worldwide pole for health innovation. Thanks to the dedicated work of our care, research and teaching teams, patients can now access this new treatment with demonstrated effectiveness and impact on quality of life," said Sylvain Lemieux, President and CEO, Centre intgr universitaire de sant et de services sociaux (CIUSSS) de l'Est-de-l'le-de-Montral.

About Kymriah Kymriah (tisagenlecleucel), a CD19-directed genetically modified autologous T-cell immunocellular therapy, is approved to treat two life-threatening cancers that have limited treatment options and historically poor outcomes, demonstrating the critical need for new therapies for these patients.

Kymriah is approved by Health Canada for use in pediatric and young adult patients 3 to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) who are refractory, have relapsed after allogenic stem cell transplant (SCT) or are otherwise ineligible for SCT, or have experienced second or later relapse; and for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphomai.

Kymriah is a one-time treatment that uses a patient's own T cells to fight and kill cancer cells. Bringing this innovative therapy to Canadian patients requires collaboration among many health system stakeholders.

Kymriah (tisagenlecleucel) Important Safety InformationThe full prescribing information for Kymriah can be found at: http://www.novartis.ca

Novartis Leadership in Cell and Gene TherapyNovartis is at the forefront of investigational immunocellular therapy and was the first pharmaceutical company to significantly invest in CAR-T research, work with pioneers in CAR-T and initiate global CAR-T trials. Kymriah, the first approved CAR-T cell therapy in Canada, is the cornerstone of this strategy. Active research programs are underway targeting other hematologic malignancies and solid tumors, and include efforts focused on next generation CAR-Ts that involve simplified manufacturing schemes and gene edited cells.

About Novartis in CanadaNovartis Pharmaceuticals Canada Inc., a leader in the healthcare field, is committed to the discovery, development and marketing of innovative products to improve the well-being of all Canadians. In 2018, the company invested $52 million in research and development in Canada. Located in Dorval, Quebec, Novartis Pharmaceuticals Canada Inc. employs approximately 1,000 people in Canada and is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. For further information, please consult http://www.novartis.ca.

About NovartisNovartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach more than 750 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at http://www.novartis.com.

Kymriah is a registered trademark.

References_____________________________________________i Novartis Pharmaceuticals Canada Inc., Kymriah Product Monograph. January 7, 2019.ii Quebec Ministry of Health and Social Services press release. October 8, 2019. Available at: https://www.newswire.ca/fr/news-releases/la-therapie-car-t-cell-maintenant-disponible-au-quebec-821953237.html

SOURCE Novartis Pharmaceuticals Canada Inc.

For further information: Novartis Media Relations, Daphne Weatherby, Novartis Corporate Communications, +1 514 633 7873, E-mail: camlph.communications@novartis.com

http://www.novartis.ca

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Novartis completes certification of initial sites in Quebec for first approved Canadian CAR-T therapy, Kymriah (tisagenlecleucel)(i) - Canada NewsWire

Bone Marrow Stem Cells Comments Off on Novartis completes certification of initial sites in Quebec for first approved Canadian CAR-T therapy, Kymriah (tisagenlecleucel)(i) – Canada NewsWire | October 9th, 2019

Registration is now open for World Cord Blood Day 2019 (November 15th) including the official online conference (free event) which will feature numerous cord blood transplant doctors and cellular therapy researchers such as Dr. Joanne Kurtzberg, Dr. Karen Ballen, Dr. Elizabeth Shpall, Dr. Wise Young and Dr. Filippo Milano. In addition, free educational events will be held around the globe.

TUCSON, Ariz., Oct. 9, 2019 /PRNewswire/ -- World Cord Blood Day (November 15th, 2019) is a free event and open to the public. In addition to events worldwide, World Cord Blood Day will feature a free online conference. Renowned researchers and leading transplant doctors will give introductory presentations for the public as well as academic lectures specifically designed for healthcare professionals.

Attendees will learn about the 40,000+ cord blood transplants performed since 1988 to treat over 80 life-threatening diseases including sickle cell anemia, thalassemia, lymphoma and leukemia. In addition, attendees will learn about exciting advances in the emerging field of regenerative medicine to potentially treat autism, cerebral palsy, spinal cord injury and more.

As the host and organizer of World Cord Blood Day 2019, Save the Cord Foundation is proud to announce the following speakers for this year's program (in order of appearance): Dr. Joanne Kurtzberg (Duke Department of Pediatrics, Duke Center for Autism and Brain Development), Dr. Karen Ballen (University of Virginia), Dave Murphy and Monroe Burgess (Quick Specialized Healthcare Logistics), Dr. Wise Young (Rutgers University), Dr. Elizabeth Shpall (MD Anderson Cancer Center), Dr. Filippo Milano (Fred Hutchinson Cancer Research Center). In addition, attendees will hear from Dr. Alexes Harris who beat cancer thanks to a cord blood transplant from a donor and young Luke Fryer who was treated for cerebral palsy with his own cord blood in a clinical trial.

The morning session will focus on the success of cord blood transplants over the past 30 years and how transplant doctors use cord blood stem cells today, namely, to fight blood cancer. The afternoon session will look at new directions in cord blood research. Attendees will receive updates on several ground-breaking clinical trials using cord blood in regenerative medicine, cellular therapy and more. To view the full agenda, please visit: https://www.worldcordbloodday.org/online-medical-conference-agenda.html

Organized and hosted by Save the Cord Foundation (501c3 non-profit), this year's event is officially sponsored by Quick Specialized Healthcare Logistics. Inspiring Partners include the Cord Blood Association (CBA), Be the Match (NMDP), World Marrow Donor Association (WMDA-Netcord), AABB Center for Cellular Therapy and Foundation for the Accreditation of Cellular Therapy (FACT).

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Visit http://www.WorldCordBloodDay.org to learn how you can participate and/or host an event. Join us on social media using the hashtags: #WCBD19 and #WorldCordBloodDay.

About Save the Cord Foundation

Save the Cord Foundation (a 501c3 non-profit) was established to advance cord blood education. The Foundation provides non-commercial information to parents, health professionals and the public regarding methods for saving cord blood, as well as current applications using cord blood and the latest research. Learn more at http://www.SaveTheCordFoundation.org.

About Quick Specialized Healthcare Logistics

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PENNY Lancaster was reduced to tears as she handed five-year-old Ronnie Musselwhite the Young Hero gong at The Suns Who Cares Wins health awards last night.

Spurs fan Ronnie bravely offered to give his older sister Ebonie a bone marrow transplant last year.

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Eight-year-old Ebonie had leukaemia and it was her only hope.

Mum Christine Jenkins, 40, said: Ronnies stem cells worked perfectly. They did what they were supposed to do but the leukaemia came back somewhere new.

Ebonie, of Crawley, West Sussex, nominated her younger brother before her death in June.

Rod Stewarts partner Penny chatted with Ronnie about his love of football and Spurs.

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She said: To say I am humbled to be here is an understatement. Sometimes you think life has turned a corner on you, but then someone else turns up to give you some inspiration.

"The courage this little man has shown is absolutely incredible. Hes only five years old, hes lost a sister.

"He was incredibly shy to stand up in front of everyone to collect his award, but he again was so brave.

Christine said: We want Ronnie to know that what he did still worked, was still brave, even though he lost his sister.

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PM Boris Johnson was also at the awards held at The Suns London HQ near The Shard and paid tribute to our NHS heroes.

He presented an award to a pair of quick-thinking hospital porters who saved the life of a seven-week-old baby boy.

Nick Evans, 48, and Ruth Lowe, 47, sprang into action after Logan Clifford stopped breathing.

His parents, Sarah and Mike were visiting a relative at the Princess Royal Hospital in Telford, Shrops, when they noticed Logans lips had turned blue.

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Sarahs screams alerted Ruth, who shouted for Nick. He grabbed Logan and performed CPR as he ran half a mile down the corridor to A&E.

Nick continued CPR until the resuscitation team took over and the porters stayed by Logans parents side until they knew he was going to be OK. Sarah, 30, has called the two porters my heroes.

As he handed the pair the Ultimate Lifesaver trophy, the PM said: The NHS is revered around the world, and in no small part due to the heroes working in it every day.

He added: My experience of the NHS is like everybody else in the NHS - one of admiration and love.

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"It is the most extraordinary institution in the world. If our country was an omelette then the NHS is the egg white that holds the great British cake together.

Virgin Radio DJ Chris Evans presented the Best Nurse gong to Liz Monaghan, 53. She set up the widely praised Purple Rose initiative, which aims to improve the care for patients and their loved ones in the last days of their life.

Liz, who works at the Florence Nightingale Hospice, based at the Stoke Mandeville Hospital in Aylesbury, Bucks, said: Im a little embarrassed to have won. Im a small part of a big team.

DJ Chris said: Youve got to prepare yourself for nights like this because otherwise they hit you like an express train.

Who Cares Wins Awards: The winners

BEST HEALTH CHARITY

Winner: Matt Hampson Foundation

Former English rugby union player Matt Hampson set up a charity to help others after being left paralysed in a scrum in 2005.

Other nominees: Superhero Foundation and Team Domenica

BEST NEONATAL SPECIALIST

Winner: Professor Kypros Nicolaides

Professor Nicolaides performed pioneering keyhole surgeon on Sherrie Sharps unborn son Jaxon. By extraordinary coincidence, as a young surgeon, he also operated on Sherries mother when she was in the womb.

Other nominees: Dr Vesna Pavasovic and Professor Massimo Caputo

UNSUNG HERO

Winner: Therapeutic Care Volunteers at South Tees NHS Foundation Trust

30 therapeutic care volunteers, who all have a learning or physical disability, give up their time to support patients with spinal injuries at The James Cook University Hospital in Middlesbrough. They include Ify Nwokoro.

Other nominees: Ben Slack and Rob Allen

GROUNDBREAKING PIONEER

Winner: Guys and St Thomas London Auditory Brainstem Implant (ABI) Service

Leia Armitage, eight, was born with a rare form of deafness and was never expected to speak. But she now can thanks to pioneering brain surgery and speech therapy carried out by Guys and St Thomas London Auditory Brainstem Implant (ABI) Service.

Other nominees: Dr Helen Spencer and Girish Vajramani

BEST DOCTOR

Winner: Dr Matthew Boulter

Dr Boulter served in Afghanistan, teaches wild trauma to army medics and his surgery became the first in Cornwall to be given veteran friendly accreditation.

Other nominees: Margaret France and Dr Bijay Sinha

BEST MIDWIFE

Winner: Jane Parke

Jane helped deliver the youngest surviving twin boys in Britain when they were born at 22 weeks last year. She flew 190 miles with their mum Jennie Powell to a specialist neonatal unit.

Other nominees: Charlotte Day and Nagmeh Teymourian

ULTIMATE LIFESAVER

Winner: Ruth Lowe and Nick Evans

Porters Ruth and Nick saved the life of Sarah and Mike Cliffords seven-week-old baby Logan. He stopped breathing as they walked through the main entrance of The Princess Royal Hospital in Telford to visit a sick relative.

Other nominees: Dr Mark Forrest and Mike Merrett

BEST NURSE

Winner: Liz Monaghan

Liz is the Matron of the Florence Nightingale Hospice in Aylesbury, Bucks, and came up with the idea for the widely praised Purple Rose initiative to improve the care for patients in the last days of their lives.

Other nominees: Margaret Ballard and Carlton DeCosta

MENTAL HEALTH HERO

Winner: Ben West

Ben lost his brother Sam, 15, to suicide last year and since his death, has campaigned tirelessly to raise awareness for mental health.

Other nominees: Beth Gregan and Catherine Benfield

YOUNG HERO

Winner: Ronnie Musselwhite

Ronnie offered to help his sister Ebonie by giving her a bone marrow transplant when she was diagnosed with a rare form of leukaemia. Ebonie nominated her brother for his bravery before she died in June.

Other nominees: Bella Field and Kaitlyn Wright

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I only walked ten metres into the room tonight and I already nearly burst into tears three times.

TV star Christine Lampard gave the Best Neonatal Specialist award to Prof Kypros Nicolaides, 66.

He was nominated by Sherrie Sharp, 29, of Horsham, West Sussex, for saving the life of her unborn baby son and her own.

After scans revealed Jaxson had spina bifida, Sherrie was offered a termination. But she contacted Prof Nicolaides, a surgeon at Kings College Hospital, London.

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He had saved her life 30 years earlier when she developed a rare blood disorder in her mums womb.

He agreed to perform ground-breaking surgery on Jaxson while he was in Sherries womb.

Prof Nicolaides said: I was delighted to be able to help. Sherrie said: He has saved so many generations of my family. Hes our guardian angel.

The Who Cares Wins Awards were set up in 2017 by The Sun to honour the nations heroic doctors, nurses, midwives, other NHS staff and volunteers.

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The Duchess of York presented an award to the parents of Natasha Ednan-Laperouse, 15, who died of an allergic reaction to a sandwich from Pret.

The duchess said: Can I just say to The Sun, I think youre incredible. Every minute Im sitting there and thinking Im so lucky. The NHS, The Sun and all of you, this is what makes Britain so great.

Lorraine Kelly, who presented the awards, said: Earlier on this year my dad was very sick and we honestly thought we were going to lose him.

"It was really difficult and it was only because of the efforts of the NHS hes still here. Its fantastic.

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Who Cares Wins Awards: The winners

BEST HEALTH CHARITY

Nominees: Superhero Foundation

Team Domenica

Winner: Matt Hampson Foundation

Former English rugby union player Matt Hampson set up a charity to help others after being left paralysed in a scrum in 2005.

BEST NEONATAL SPECIALIST

Nominees: Dr Vesna Pavasovic

Professor Massimo Caputo

Winner: Professor Kypros Nicolaides

Professor Nicolaides performed pioneering keyhole surgeon on Sherrie Sharps unborn son Jaxon. By extraordinary coincidence, as a young surgeon, he also operated on Sherries mother when she was in the womb.

UNSUNG HERO

Nominees: Ben Slack

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Penny Lancaster is reduced to tears as she gives bone marrow donor Ronnie Musselwhite, 5, The Suns Young H - The Scottish Sun

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The new stem cells migrate to the cavities of the large bones and begin producing healthy, normal blood cells. The type of transplant you receive depends on your disease and the availability of a suitable donor.

Autologous (self-transplant): Your own cells are collected and frozen for later use. Autologous transplants are most commonly performed for lymphomas, multiple myeloma, testicular cancer and leukemia.

Syngeneic (identical twin transplant): Stem cells are donated by an identical twin, which is an ideal donor because of the matching genetic identity between donor and recipient.

Allogeneic (donor transplant): Stem cells are collected from a relative or an unrelated donor whose tissue type matches closely with that of the patient, or from umbilical cord blood. Allogeneic transplants are most commonly done for leukemias and bone marrow or immune system failure diseases.

At Winship, our Bone Marrow Transplant Center treats leukemia, lymphoma, multiple myeloma and plasma cell disorders; sickle cell anemia, testicular cancer and bone marrow failures.

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Bone Marrow and Stem Cell Transplant Center | Winship ...

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JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Abstract

Bone has well documented natural healing capacity that normally is sufficient to repair fractures and other common injuries. However, the properties of bone change throughout life, and aging is accompanied by increased incidence of bone diseases and compromised fracture healing capacity, which necessitate effective therapies capable of enhancing bone regeneration. The therapeutic potential of adult mesenchymal stem cells (MSCs) for bone repair has been long proposed and examined. Actions of MSCs may include direct differentiation to become bone cells, attraction and recruitment of other cells, or creation of a regenerative environment via production of trophic growth factors. With systemic aging, MSCs also undergo functional decline, which has been well investigated in a number of recent studies. In this review, we first describe the changes in MSCs during aging and discuss how these alterations can affect bone regeneration. We next review current research findings on bone tissue engineering, which is considered a promising and viable therapeutic solution for structural and functional restoration of bone. In particular, the importance of MSCs and bioscaffolds is highlighted. Finally, potential approaches for the prevention of MSC aging and the rejuvenation of aged MSC are discussed.

MSC

Aging

Stem cell niche

Bone healing

Rejuvenation

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2018 Published by Elsevier Ltd.

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JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.Abstract

Oxidative stress on transplanted bone marrow-derived mesenchymal stem cells (BMSCs) during acute inflammation is a critical issue in cell therapies. N-acetyl-L cysteine (NAC) promotes the production of a cellular antioxidant molecule, glutathione (GSH). The aim of this study was to investigate the effects of pre-treatment with NAC on the apoptosis resistance and bone regeneration capability of BMSCs. Rat femur-derived BMSCs were treated in growth medium with or without 5mM NAC for 6h, followed by exposure to 100MH2O2 for 24h to induce oxidative stress. Pre-treatment with NAC significantly increased intracellular GSH levels by up to two fold and prevented H2O2-induced intracellular redox imbalance, apoptosis and senescence. When critical-sized rat femur defects were filled with a collagen sponge containing fluorescent-labeled autologous BMSCs with or without NAC treatment, the number of apoptotic and surviving cells in the transplanted site after 3 days was significantly lower and higher in the NAC pre-treated group, respectively. By the 5th week, significantly enhanced new bone formation was observed in the NAC pre-treated group. These data suggest that pre-treatment of BMSCs with NAC before local transplantation enhances bone regeneration via reinforced resistance to oxidative stress-induced apoptosis at the transplanted site.

Acute inflammation

Apoptosis

Cell conditioning

Glutathione

Local transplantation

Senescence

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2018 Elsevier Ltd. All rights reserved.

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Preconditioning of bone marrow-derived mesenchymal stem ...

Bone Marrow Stem Cells Comments Off on Preconditioning of bone marrow-derived mesenchymal stem … | May 20th, 2019

Bone marrow failure occurs in individuals who produce an insufficient amount of red blood cells, white blood cells or platelets. Red blood cells transport oxygen to be distributed throughout the bodys tissue. White blood cells fight off infections that enter the body. Bone marrow also contains platelets, which trigger clotting, and thus help stop the blood flow when a wound occurs. [1]

Bone marrow failure is associated with three types of diseases, Fanconi anemia (FA), dyskeratosis congenita, and aplastic anemia. Fanconi anemia is an inherited blood disorder due to abnormal breakages in DNA genes. It is linked to hyperpigmentation, which is the darkening of an area of skin or nails caused by increased melanin. According to Histopathology, However, in about 30% of FA patients no physical abnormalities are found.[2] Dyskeratosis congenita often affects multiple parts of the body. Individuals with this disorder usually show changes in skin pigmentations, unusual fingernail growth, and mucosa leukoplakia; the inner part of the mouth is encased with white patches that may never resolve.[2] Aplastic anemia happens when bone marrow doesnt produce enough new blood cells throughout the body. Aplastic anemia is an acquired autoimmune disease, which occurs when the immune system mistakenly attacks and destroys healthy body tissue.[3]

Bone marrow failure in both children and adults can be either inherited or acquired. Inherited bone marrow failure is often the cause in young children, while older children and adults may acquire the disease later in life.[4] A maturation defect in genes is a common cause of inherited bone marrow failure.[5] The most common cause of acquired bone marrow failure is aplastic anemia.[5] Working with chemicals such as benzene could be a factor in causing the illness. Other factors include radiation or chemotherapy treatments, and immune system problems.

The two most common signs and symptoms of bone marrow failure are bleeding and bruising. Blood may be seen throughout the gums, nose or the skin, and tend to last longer than normal. Children have a bigger chance of seeing blood in their urine or stools, which results in digestive problems with an unpleasant scent. Individuals with this condition may also encounter tooth loss or tooth decay. Chronic fatigue, shortness of breath, and recurrent colds can also be symptoms of bone marrow failure.[6]

The type of treatment depends on the severity of the patients bone marrow failure disease. Blood transfusion is one treatment. Blood is collected from volunteer donors who agree to let doctors draw blood stem cells from their blood or bone marrow for transplantation.[7] Blood that is taken straight from collected blood stem cells is known as peripheral blood stem cell donation. A peripheral stem cell donor must have the same blood type as the patient receiving the blood cells. Once the stem cells are in the patients body through an IV, the cells mature and become blood cells. Before donation, a drug is injected into the donor, which increases the number of stem cells into their body. Feeling cold and lightheaded, having numbness around the mouth and cramping in the hands are common symptoms during the donation process. After the donation, the amount of time for recovery varies for every donor, But most stem cell donors are able to return to their usual activities within a few days to a week after donation.[7]

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Bone Marrow Stem Cells Comments Off on Bone marrow failure – Wikipedia | May 12th, 2019

When the healthy stem cells come from you, the procedure is called an autologous transplant. When the stem cells come from another person, called a donor, it is an allogeneic transplant. Blood or bone marrow transplants most commonly are used to treat blood cancers or other kinds of blood diseases that decrease the number of healthy blood cells in the body. These transplants also may be used to treat other disorders.

For allogeneic transplants, your doctor will try to find a donor whose blood cells are the best match for you. Your doctor will consider using cells from your close family members, from people who are not related to you and who have registered with the National Marrow Donor Program, or from publicly stored umbilical cord blood. Although it is best to find a donor who is an exact match to you, new transplant procedures are making it possible to use donors who are not an exact match.

Blood or bone marrow transplants are usually performed in a hospital. Often, you must stay in the hospital for one to two weeks before the transplant to prepare. During this time, you will have a narrow tube placed in one of your large veins. You may be given medicine to make you sleepy for this procedure. You also will receive special medicines and possibly radiation to destroy your abnormal stem cells and to weaken your immune system so that it wont reject the donor cells after the transplant.

On the day of the transplant, you will be awake and may get medicine to relax you during the procedure. The stem cells will be given to you through the narrow tube in your vein. The stem cells will travel through your blood to your bone marrow, where they will begin making new healthy blood cells.

After the transplant, your doctor will check your blood counts every day to see if new blood cells have started to grow in your bone marrow. Depending on the type of transplant, you may be able to leave, but stay near the hospital, or you may need to remain in the hospital for weeks or months. The length of time will depend on how your immune system is recovering and whether or not the transplanted cells stay in your body. Before you leave the hospital, the doctors will give you detailed instructions that you must follow to prevent infection and other complications. Your doctor will keep monitoring your recovery, possibly for up to oneyear.

Although blood or bone marrow transplant is an effective treatment for some conditions, the procedure can cause early or late complications. The required medicines and radiation can cause nausea, vomiting, diarrhea, tiredness, mouth sores, skin rashes, hair loss, or liver damage. These treatments also can weaken your immune system and increase your risk for infection. Some people may experience a serious complication called graft-versus-host disease if the donated stem cells attack the body. Other people may reject the donor stem cells after the transplant, which can be an extremely serious complication.

VisitBlood-Forming Stem Cell Transplantsfor more information about this topic.

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Blood and Bone Marrow Transplant | National Heart, Lung ...

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Stromal vascular fraction was dramatically better than bone marrow concentrate in its ability to differentiate into cartilage.Two other important features were also well documented in this study. SVF created significantly more colony forming units than BMC, another significant predictor of healing response. Perhaps most importantly, SVF was dramatically better than BMC in its ability to differentiate into cartilage.

Second, a study by Han Chao et al has also demonstrated that fat derived stem cells also have a higher proliferation potential for neural tissue and are a better source for not only cartilage regeneration but also for nervous system regeneration.

The studies gave a very comprehensive look at comparing BMC and SVF in the ability to repair cartilage damage in a same procedure protocol. Every significant measurement comparing bone marrow to adipose tissue for stem cell harvesting demonstrated that adipose derived stem cells provided better cell content and superior ability to differentiate into cartilage than bone marrow. Our extensive clinical experience with the procedure for Colorado patients suffering from pain in the knees, other joints, soft tissue, and a wide range of back problems clearly demonstrates the same.

Using the most effective combination of autologous stem cell sources is one of several criteria to identify a legitimate stem cell clinic. Other important characteristics we recommend paying attention to when choosing a stem cell clinic, include the presence of a physician who owns and operates the clinic, X-ray guided injections administered by a trained injection specialist, and a clinic that takes time to discuss your questions. A review of your imaging and clinical data is needed in order to determine if stem cell therapy is right for you.

*Individual patient results may vary. Contact us today to find out if stem cell therapy may be able to help you.

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Stem Cells from Fat vs. Bone Marrow Best Sources for ...

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Snow and ice cause cars to stall out on the road to their destination. In patients with CLL, its their stem cells that stall out and researchers want to know why.

For patients who have chronic lymphocytic leukemia, fighting off a serious infection can be difficult and often is just not possible. And a team of Mayo researchers is starting to find out why in a paper published recently in the journal Leukemia.

What is Chronic Lymphocytic Leukemia?

This disease is cancer of an immune cell called a B lymphocyte. These cells form in bone marrow and migrate out to patrol in the blood stream and lymphoid organs. But in chronic lymphocytic leukemia, the immune system is depleted, a state called immunodeficiency. Because of that, people with this type of leukemia are prone to serious infections and the diseases those may cause. They are also prone to developing other types of cancer.

And its those resulting problems that may ultimately contribute to death explains Kay Medina, Ph.D., a Mayo Clinic immunologist. Dr. Medina specializes in how immune cells develop from bone marrow stem cells.

In our bone marrow, stem cells convert to red blood cells, platelets or a variety of immune cells. Those are then sent into the blood stream where they do their job. Red blood cells replace cells that are worn out.

White blood cells patrol the byways of our circulation, chasing down everything from cellular debris to bacteria to virus particles.But not in patients with chronic lymphocytic leukemia.

Joining the Team

Research on chronic lymphocytic leukemia is going on in several labs at Mayo Clinic. Dr. Medina got involved after speaking with colleagues Wei Ding, M.B.B.S, Ph.D., and Neil Kay, M.D., both chronic lymphocytic leukemia physician researchers.

Mayo has a strong tradition of encouraging physician/basic research collaborations to advance knowledge of disease mechanisms, development, and assessment of new treatment approaches, says Dr. Medina.

The basic research helps us understand the cause of the disease, in this case the leukemia cell, but it also helps to understand what the disease does to other parts of the body, such as the lymph nodes, spleen, blood and bone marrow, she says.

Bone marrow is the organ that replenishes all cells in the immune system but has not been evaluated for functional proficiency in CLL patients, explains Dr. Medina.

Checking out the Cells and their Environment

Kay Medina, Ph.D.

Dr. Medinas team, with funding from Mayo Clinics Center for Biomedical Discovery, decided to look at bone marrow stem cells and their ability to generate all blood cell types. Some of the immune deficiency may be the result of treatment, but untreated patients have the same problem. The chronic nature of the disease itself may also dampen immune activity. But Dr. Medina explains that the leukemia cells may promote an environment that suppresses immune function.

Our research seeks to add to the discussion by identifying additional ways patients with CLL are unable to fight off tumors and other diseases, says Dr. Medina.

In a paper published late last year, Dr. Medina and her team, including first author Bryce Manso who is a student in the Mayo Clinic Graduate School of Biomedical Sciences, examined bone marrow and blood samples from chronic lymphocytic leukemia patients and healthy controls to determine the frequency of bone marrow stem cells in each sample and how well they did their job.

Bryce Manso, presenting a poster to a conference attendee.

The authors reported that, in general, samples from patients with chronic lymphocytic leukemia have fewer stem cells in their bone marrow, and those stem cells that remain work less well than stem cells from controls.

Stalled-Out Bone Marrow Stem Cells

As to why this happens, the authors found that it was linked to loosening controls for the on/off switches which regulate this process, proteins called transcription factors. These proteins regulate key functions in the cell, and are out of whack in samples from chronic lymphocytic leukemia patients. They may prevent bone marrow stem cells from pursuing a pathway for development; stalling-out their ability to differentiate, resulting in decreased production of important blood cells that provide the first line of defense against infectious agents.

But, Dr. Medina cautions, there is more to this story.

This is an emerging area of research in that its both a unique explanation for the clinical problem of immune deficiency and it has been minimally studied, says Dr. Medina. Future studies are planned to look at specific transcription factors that control stem cell differentiation as well as how the presence of leukemic cells in the bone marrow alter blood cell development. They will then relate this information to clinically relevant complications reported in chronic lymphocytic leukemia patients, she says.

Basic Research to Improve Patient Care

Dr. Medina, her team, and their clinical colleagues hope that by understanding how bone marrow function is impaired in chronic lymphocytic leukemia patients, they can develop unique strategies to boost bone marrow function or find alternate treatments that do not block or modify marrow function.

Through this work we hope to find ways to reduce infections and the incidence of second cancers in chronic lymphocytic leukemia patients. Our research has the potential to improve quality of life as well as extend the lives of these patients says Dr. Medina.

###

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Tags: basic science, blood cancer, cancer, Center for Biomedical Discovery, chronic lymphocytic leukemia, Findings, immunology, Kay Medina, leukemia, Mayo Clinic Cancer Center, Neil Kay, News, Progress Updates, Wei Ding

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Bone Marrow Stem Cells Stall Out in Chronic Lymphocytic ...

Bone Marrow Stem Cells Comments Off on Bone Marrow Stem Cells Stall Out in Chronic Lymphocytic … | April 2nd, 2019

Stem cell therapies have come a long way since the 1970s and 1980s. Today the ethical issues of harvesting stem cells have long been resolved through the discovery of several sources of potent stem cell types. Common sources include in the umbilical cord and placenta (post birth), bone marrow, and the fatty layer that lies just beneath everyones skin (adipose fat tissue). Of these resources, by far the most commonly accessed in the United States are adipose fat and bone marrow stem cells.The National Stem Cell Institute (NSI), a leading stem cell clinic in the U.S., has seen the development of these living resources usher in an exciting new age known as regenerative medicine. Because of their potency and new technologies that allow ease of access, stem cells are changing the very face of medicine. In particular, the harvesting of bone marrow stem cells has developed into a procedure that is minimally invasive, far more comfortable than bone marrow harvesting of the past, and able to be complete in just a few hours.Some Basics About Bone Marrow Stem CellsBone marrow is the living tissue found in the center of our bones. Marrow is a soft, sponge-like tissue. There are two types of bone marrow: red marrow and yellow marrow. In adults, red marrow is found mainly in the central skeleton, such as the pelvis, sternum, cranium, ribs, vertebrae, and scapulae. But it is also found in the ends of long bones such as in the arms and legs.When it comes to bone marrow stem cells, red marrow is what its all about. Red marrow holds an abundance of them. Stem cells are a kind of protocell that has not yet been assigned an exact physical or neurological function. You can think of them as microscopic packets of potential that stay on high alert for signals telling them where they are needed and what type of cell they need to become.Bone marrow stem cells are multipotent, which means they have the ability to become virtually any type of tissue cell, including:

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Bone Marrow Stem Cells | NSI Stem Cell

Bone Marrow Stem Cells Comments Off on Bone Marrow Stem Cells | NSI Stem Cell | March 31st, 2019

Overview

If you are planning to donate stem cells, you have agreed to allow doctors to draw bone marrow stem cells from either your blood or bone marrow for transplantation.

There are two broad types of stem cells: embryonic and bone marrow stem cells. Embryonic stem cells are studied in therapeutic cloning and other types of research. Bone marrow stem cells are formed and mature in the bone marrow and are then released into the bloodstream. This type of stem cell is used in the treatment of cancers.

In the past, surgery to draw bone marrow stem cells directly from the bone was the only way to collect stem cells. Today, however, it's more common to collect stem cells from the blood. This is called peripheral blood stem cell donation.

Stem cells can also be collected from umbilical cord blood at birth. However, only a small amount of blood can be retrieved from the umbilical cord, so this type of transplant is generally reserved for children and small adults.

Every year, thousands of people in the U.S. are diagnosed with life-threatening diseases, such as leukemia or lymphoma, for which a stem cell transplant is the best or the only treatment. Donated blood stem cells are needed for these transplants.

You might be considering donating blood or bone marrow because someone in your family needs a stem cell transplant and doctors think you might be a match for that person. Or perhaps you want to help someone else maybe even someone you don't know who's waiting for a stem cell transplant.

Bone marrow stem cells are collected from the posterior section of the pelvic bone under general anesthesia. The most serious risk associated with donating bone marrow involves the use and effects of anesthesia during surgery. After the surgery, you might feel tired or weak and have trouble walking for a few days. The area where the bone marrow was taken out might feel sore for a few days. You can take a pain reliever for the discomfort. You'll likely be able to get back to your normal routine within a couple of days, but it may take a couple of weeks before you feel fully recovered.

The risks of this type of stem cell donation are minimal. Before the donation, you'll get injections of a medicine that increases the number of stem cells in your blood. This medicine can cause side effects, such as bone pain, muscle aches, headache, fatigue, nausea and vomiting. These usually disappear within a couple of days after you stop the injections. You can take a pain reliever for the discomfort. If that doesn't help, your doctor can prescribe another pain medicine for you.

For the donation, you'll have a thin, plastic tube (catheter) placed in a vein in your arm. If the veins in your arms are too small or have thin walls, you may need to have a catheter put in a larger vein in your neck, chest or groin. This rarely causes side effects, but complications that can occur include air trapped between your lungs and your chest wall (pneumothorax), bleeding, and infection. During the donation, you might feel lightheaded or have chills, numbness or tingling around your mouth, and cramping in your hands. These will go away after the donation.

If you want to donate stem cells, you can talk to your doctor or contact the National Marrow Donor Program, a federally funded nonprofit organization that keeps a database of volunteers who are willing to donate.

If you decide to donate, the process and possible risks of donating will be explained to you. You will then be asked to sign a consent form. You can choose to sign or not. You won't be pressured to sign the form.

After you agree to be a donor, you'll have a test called human leukocyte antigen (HLA) typing. HLAs are proteins found in most cells in your body. This test helps match donors and recipients. A close match increases the chances that the transplant will be a success.

If you sign up with a donor registry, you may or may not be matched with someone who needs a blood stem cell transplant. However, if HLA typing shows that you're a match, you'll undergo additional tests to make sure you don't have any genetic or infectious diseases that can be passed to the transplant recipient. Your doctor will also ask about your health and your family history to make sure that donation will be safe for you.

A donor registry representative may ask you to make a financial contribution to cover the cost of screening and adding you to the registry, but this is usually voluntary. Because cells from younger donors have the best chance of success when transplanted, anyone between the ages of 18 and 44 can join the registry for free. People ages 45 to 60 are asked to pay a fee to join; age 60 is the upper limit for donors.

If you're identified as a match for someone who needs a transplant, the costs related to collecting stem cells for donation will be paid by that person or by his or her health insurance.

Collecting stem cells from bone marrow is a type of surgery and is done in the operating room. You'll be given an anesthetic for the procedure. Needles will be inserted through the skin and into the bone to draw the marrow out of the bone. This process usually takes one to two hours.

After the bone marrow is collected, you'll be taken to the recovery room while the anesthetic wears off. You may then be taken to a hospital room where the nursing staff can monitor you. When you're fully alert and able to eat and drink, you'll likely be released from the hospital.

If blood stem cells are going to be collected directly from your blood, you'll be given injections of a medication to stimulate the production of blood stem cells so that more of them are circulating in your bloodstream. The medication is usually started several days before you're going to donate.

During the donation, blood is usually taken out through a catheter in a vein in your arm. The blood is sent through a machine that takes out the stem cells. The rest of the blood is then returned to you through a vein in your other arm. This process is called apheresis. It takes two to six hours and is done as an outpatient procedure. You'll typically undergo two to four apheresis sessions, depending on how many blood stem cells are needed.

Recovery times vary depending on the individual and type of donation. But most blood stem cell donors are able to return to their usual activities within a few days to a week after donation.

Recovery times vary depending on the individual and type of donation. But most blood stem cell donors are able to return to their usual activities within a few days to a week after donation.

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Dec. 20, 2018

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Blood and bone marrow stem cell donation - Mayo Clinic

Bone Marrow Stem Cells Comments Off on Blood and bone marrow stem cell donation – Mayo Clinic | March 24th, 2019

Bone Marrow (BM) contains hematopoietic stem/progenitor cells, which have the potential to self-renew, proliferate, and differentiate into multi-lineage blood cells. Multipotent, non-hematopoietic stem cells, such as mesenchymal stem cells, can be isolated from human BM as well. These non-hematopoietic, mesenchymal stem cells are capable of both self-renewal and differentiation into bone, cartilage, muscle, tendons, and fat. BM is drawn into a 60cc syringe containing heparin (80 U/mL of BM) from the posterior iliac crest, 25 mL/site, from a maximum of four sites.CustomizationLet us know how we can customize your product today Custom InquiryDonor CriteriaAge18-65 years oldWeight>= 130 lbsScreened before donationHIV (HIV 1 & 2 Ab)HBV (Surface Antigen HbsAg)HCV (HCVAb)Donation FrequencyMinimum 10 weeks between donationsDonors with any of the following will be excluded from donatingPregnancyHistory of heart, lung, liver, or kidney diseaseHistory of asthmaBlood and bleeding disorders including sickle cell diseaseNeurologic disordersAutoimmune disordersCancerDiabetesOther CriteriaMust be in general good healthMust have accessible hipsComplete Blood Count lab test must meet protocol specsRequired to sign procedure-specific consent form

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Whole Bone Marrow - AllCells.com

Bone Marrow Stem Cells Comments Off on Whole Bone Marrow – AllCells.com | March 23rd, 2019

Before the transplant admission:

When the healthcare team decides that BMT is the best treatment option for your child, they will schedule a lengthy conversation with you to explain the procedure. They will explain the many risks associated with BMT, as well as what you can expect before, during, and after the transplant.

Your child will undergo testing to make sure he/she is healthy enough to withstand the rigors of transplant. Testing will include evaluation of the heart function with electrocardiogram (ECG) and kidney and liver function, and infection status. Depending upon the disease, a bone marrow aspirate and spinal tap may be performed.

When your child is deemed healthy enough for BMT, physicians will usually insert a central line catheter that allows easy access to a large vein in the chest. The catheter will be used to deliver the new stem cells, as well as blood, antibiotics, and other medications during treatment.

Preparation Before Transplant:

Your child will be given preparative treatment, called conditioning before the transplant. Conditioning includes high doses of chemotherapy and sometimes, radiation of the whole body. The type and purpose of conditioning depends upon your childs underlying diagnosis but may include:

Commonly used drugs include:

The Transplant

Once conditioning is complete, stem cells are given through a catheter. This is very similar to a blood transfusion. After traveling through the bloodstream to the bone marrow, the transplanted stem cells will begin to make red and white blood cells, and platelets.

It can take between 14 and 30 days for enough blood cells, particularly white blood cells, to be created so the body can fight infection. The identification of new blood cells and an increase in white blood cells following BMT is called engraftment. Until then, your child will be at a high risk for infection, anemia, and bleeding. Your child will remain in the hospital until he or she is well enough for discharge.

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Bone Marrow Transplant | CureSearch

Bone Marrow Stem Cells Comments Off on Bone Marrow Transplant | CureSearch | March 14th, 2019

Definition

A bone marrow transplant is a procedure to replace damaged or destroyed bone marrow with healthy bone marrow stem cells.

Bone marrow is the soft, fatty tissue inside your bones. The bone marrow produces blood cells. Stem cells are immature cells in the bone marrow that give rise to all of your different blood cells.

Transplant - bone marrow; Stem cell transplant; Hematopoietic stem cell transplant; Reduced intensity nonmyeloablative transplant; Mini transplant; Allogenic bone marrow transplant; Autologous bone marrow transplant; Umbilical cord blood transplant; Aplastic anemia - bone marrow transplant; Leukemia - bone marrow transplant; Lymphoma - bone marrow transplant; Multiple myeloma - bone marrow transplant

Before the transplant, chemotherapy, radiation, or both may be given. This may be done in 2 ways:

There are three kinds of bone marrow transplants:

A stem cell transplant is usually done after chemotherapy and radiation is complete. The stem cells are delivered into your bloodstream usually through a tube called a central venous catheter. The process is similar to getting a blood transfusion. The stem cells travel through the blood into the bone marrow. Most times, no surgery is needed.

Donor stem cells can be collected in two ways:

A bone marrow transplant replaces bone marrow that is either not working properly or has been destroyed (ablated) by chemotherapy or radiation. Doctors believe that for many cancers, the donor's white blood cells may attack any remaining cancer cells, similar to when white cells attack bacteria or viruses when fighting an infection.

Your health care provider may recommend a bone marrow transplant if you have:

A bone marrow transplant may cause the following symptoms:

Possible complications of a bone marrow transplant depend on many things, including:

Complications may include:

Your provider will ask about your medical history and do a physical exam. You will have many tests before treatment begins.

Before transplant, you will have 1 or 2 tubes, called catheters, inserted into a blood vessel in your neck or arms. This tube allows you to receive treatments, fluids, and sometimes nutrition. It is also used to draw blood.

Your provider will likely discuss the emotional stress of having a bone marrow transplant. You may want to meet with a counselor. It is important to talk to your family and children to help them understand what to expect.

You will need to make plans to help you prepare for the procedure and handle tasks after your transplant:

A bone marrow transplant is usually done in a hospital or medical center that specializes in such treatment. Most of the time, you stay in a special bone marrow transplant unit in the center. This is to limit your chance of getting an infection.

Depending on the treatment and where it is done, all or part of an autologous or allogeneic transplant may be done as an outpatient. This means you do not have to stay in the hospital overnight.

How long you stay in the hospital depends on:

While you are in the hospital:

After you leave the hospital, be sure to follow instructions on how to care for yourself at home.

How well you do after the transplant depends on:

A bone marrow transplant may completely or partially cure your illness. If the transplant is a success, you can go back to most of your normal activities as soon as you feel well enough. Usually it takes up to 1 year to recover fully, depending on what complications occur.

Complications or failure of the bone marrow transplant can lead to death.

Bashir Q, Champlin R. Hematopoietic stem cell transplantation. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 30.

Heslop HE. Overview and choice of donor of hematopoietic stem cell transplantation. In: Hoffman R, Benz EJ, Silberstein LE, et al, eds. Hematology: Basic Principles and Practice. 7th ed. Philadelphia, PA: Elsevier; 2018:chap 103.

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Bone marrow transplant | UF Health, University of Florida ...

Bone Marrow Stem Cells Comments Off on Bone marrow transplant | UF Health, University of Florida … | March 13th, 2019

The myth that stem cell or bone marrow donation is painful is extremely common and worryingly, it often stops people from registering to donate.

In 2016, a YouGov survey found that a shocking 34% of young men who wouldnt sign up as a stem cell donor were just tooscared that the experience would be painful.

We urgently need that to change because it couldnt be further from the truth.

I would 100% recommend it to other people. Its comfortable, painless and so worthwhile.Zachary, stem cell donor

It was painless and thats coming from someone with a fear of needles! I remember being amazed at how simple it was.Sean, stem cell donor

90% of people now donate directly from their bloodstream, in a procedure known as peripheral blood stem cell donation (PBSC).

Youll receive a series of four hormone injections to make your stem cells multiply into the bloodstream. Then youll head to a clinic, where the stem cells will be extracted from one arm, and your blood returned to the other.

And thats it. Some people report flu-like symptoms from the hormone injections, but these are usually mild and vanish within a few days.

Ive felt worse after a few bruising encounters on the football pitch. Within a week of the donation, I was back on my feet and feeling much better; all in all, its a very small price to pay for what could be achieved.Liam, bone marrow donor

Some people have asked me if it was painful or difficult. It was actually quite simple and nothing compared to what the recipient is going through at the same time.Andrew, stem cell and bone marrow donor

Just 10% of people are asked to donate from the bone marrow itself.

This is the procedure that lies at the root of the bone marrow donation is painful myth but in reality, it takes place under general anaesthetic, so you wont feel any pain while its happening.

Afterwards, youll probably feel a bit tired and bruised, and we recommend that you take a short break from work to recover. But thats all and it makes a lifesaving difference.

Tackling the myth that stem cell or bone marrow donation is painful is one of our biggest priorities.

Thats why we often ask our donors to share their stories, to bust the myths and show the world what donation is really like.

For a wide variety of donation experiences, just check out the Anthony Nolan Facebook page we usually add one or two new stories every week!

If you're aged 16-30, sign up to our lifesaving register by clicking on the link below:

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Is donating bone marrow painful? | Anthony Nolan

Bone Marrow Stem Cells Comments Off on Is donating bone marrow painful? | Anthony Nolan | February 12th, 2019