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Research method integrates human cortical organoids into developing rat brains, allowing for study of brain processes associated with disease.

This work provides a significant advance in the ability of scientists to study the cellular and circuit underpinnings of complex human brain disorders. It allows organoids to get wired in a more biologically relevant context and function in ways they cant do in a petri dish, said David Panchision, Ph.D., chief of the Developmental and Genomic Neuroscience Research Branch in the Division of Neuroscience and Basic Behavioral Science at NIMH.

ResearcherSergiu Pasca, M.D.(link is external), and colleagues at Stanford University, Stanford, California, demonstrated that a cortical organoid cultured from human stem cells can be transplanted ontoand integrated intothe developing rat brain to study certain developmental and functional processes. The findings suggest that transplanted organoids may offer a powerful tool for investigating the processes associated with disease development.

Researchers sometimes use cortical organoidsthree-dimensional cultures of human stem cells that can mirror some of the developmental processes seen in typical brainsas a model for investigating how some aspects of the human brain develops and functions. However, cortical organoids lack the connectivity seen in typical human brains, limiting their usefulness for understanding complex brain processes. Researchers have been trying to overcome some of these limitations by transplanting individual human neurons into adult rodent brains. While these transplanted neurons connect with rodent brain cells, they do not become fully integrated due to the developmental limitations of the adult rat brain.

In this study, the team of researchers advanced the use of brain organoids for research by transplanting an intact human cortical organoid into a developing rat brain. This technique creates a unit of human tissue that can be examined and manipulated. The researchers used methods previously pioneered in the Pasca lab to create cortical organoids using human-induced pluripotent stem cellscells derived from adult skin cells that have been reprogrammed into an immature stem-cell-like state. They then implanted these organoids onto the rat primary somatosensory cortex, a part of the brain involved in processing sensation.

The researchers did not detect any motor or memory abnormalities or abnormalities in brain activity in the rats that received the transplanted organoid. Blood vessels from the rat brain successfully supported the implanted tissue, which grew over time.

To understand the extent to which the organoids could integrate into the rat somatosensory cortex, the researchers infected a cortical organoid with a viral tracer that spreads through brain cells as an indicator of functional connections. After transplanting the marked organoid onto the rats primary somatosensory cortex, researchers detected the viral tracer in multiple brain areas, such as the ventrobasal nucleus and the somatosensory cortex. In addition, the researchers observed new connections between the thalamus and the transplanted area. These connections were activated using electrical stimulation and stimulation of the rats whiskers, indicating that they were receiving meaningful sensory input. Moreover, the researchers were able to activate human neurons in the transplanted organoid to modulate the rats reward-seeking behavior. The findings suggest functional integration of the transplanted organoid into specific brain pathways.

Structurally and functionally, after seven to eight months of growth, the transplanted brain organoid resembled neurons from human brain tissue more than human organoids maintained in cell culture. The fact that the transplanted organoids mirrored the structural and functional features of human cortical neurons led the researchers to wonder if they could use transplanted organoids to examine aspects of human disease processes.

The promise of this platform is not only in identifying what molecular processes underlie the advanced maturation of human neurons in living circuits and leveraging it to improve conventionalin vitromodels, but also in providing behavioral readouts for human neurons, said Dr. Pasca.

To examine this, the researchers generated cortical organoids with cells from three participants with a rare genetic disorder associated with autism and epilepsy calledTimothy syndromeand three participants without any known diseases and implanted them onto the rat brain. Both types of organoids integrated into the rat somatosensory cortex, but organoids derived from Timothy Syndrome patients displayed structural differences. These structural differences did not appear in organoids that were created from the cells of patients with Timothy Syndrome and maintained in cell culture.

These experiments suggest that this novel approach can capture processes that go beyond what we can detect with currentin vitromodels, said Dr. Pasca. This is important because many of the changes that cause psychiatric disease are likely subtle differences at the circuit level.

Grant:MH115012,DA050662,RR026917,OD030452

About the National Institute of Mental Health (NIMH):The mission of theNIMHis to transform the understanding and treatment of mental illnesses through basic and clinical research, paving the way for prevention, recovery, and cure. For more information, visit theNIMH website.

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

References

Revah, O., Gore, F., Kelley, K. W., Andersen, J., Sakai, N., Chen, X., Li, M., Birey, F., Yang, X., Saw, N. L., Baker, S. W., Amin, N. D., Kulkarni, S., Mudipalli, R., Cui, B., Nishino, S., Grant, G. A., Knowles, J. K., Shamloo, M. Paca S. P. (2022).Maturation and circuit integration of transplanted human cortical organoids(link is external).Nature

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Researchers develop method to study brain connectivity, functionality - Florida Hospital News and Healthcare Report - South Florida Hospital News

New technologies based on human cells are increasingly seen as key to reducing the time and cost in bringing drugs to market. This is an evolving area of study, though the field itself, which developed out of study into 3D cell architecture, is not new. These approaches replicate human physiology to study diseases, treatments, and for drug-development purposes. In parallel to major advances made from a medical and scientific standpoint, novel legal and ethical questions arise.

The definition of organoid is problematic and covers a range of cell culture techniques. Scientists have developed ways of culturing organ-specific tissue from human stem cells or progenitor cells to re-create important aspects of the 3D anatomy e.g. the pancreas, kidney, liver, thyroid, retina, and brain, to recapitulate key organ features. A list of definitions can be found at the end of this article.

A potential game-changer

Breakthroughs in stem cell technology and tissue engineering are driving the change. In addition to this, trends in other areas, like cell and gene therapy and personalised medicine have acted as catalysts. By simulating organ function, specific disease states can be modelled and studied. This is especially useful when looking at rare diseases, how tissue and microbiota interact, or how drugs interact with each other.

The use of organoids holds great promise in several medical-scientific areas like disease modelling, precision medicine, and transplantation. One of the most notable possibilities is to supplement or to a certain extent replace animal models during pre-clinical studies in drug development.

The field is at an early stage, but the trend is an upward one. Companies involved are seeing increasing demand for their services from pharma, biotech, research and academic institutes as well as the cosmetics industry. According to a recent market report the annual growth rate is set to increase by 37.4% during 2022-2028. Cambridge-based CN Bio recently doubled the size of its laboratory facilities due to demand. In the US, Hesperos Inc., a contract research organisation (CRO) provides a multi-organ chip platform (Human-on-a-Chip) based in Florida filed for a USD 20 million IPO. Another fascinating company is Labskin, who make full thickness human skin models, providing reproduceable results for microbiome research. Labskin just announced the first ever commercially available pigmented skin-equivalent in a joint project with Bradford University. These new models incorporate melanocytes, the cells that give skin its colour and present a huge opportunity to study melanomas.

The need for new and/or updated regulatory frameworks

For the use of these new models to be considered by regulatory authorities across the globe in the evaluation of safety and efficacy of drugs (subject to valid scientific demonstrations), regulatory frameworks will have to be adapted on a jurisdiction-by-jurisdiction basis.

In the US, the FDA Modernization Act of 2021 has been introduced to amend the Federal Food, Drug, and Cosmetic Act. The amendment strikes animal and inserts nonclinical tests or studies to be used in the evaluation of safety and efficacy of drugs, such as MPS, cell-based assays and computer models. In addition, the FDA recently approved the first clinical trial using efficacy data collected from a microphysiological system. More data may be needed to convince regulators, but the impetus - and interest - is there.

In the EU, is a 3-year Science With and For Society (SwafS) project, funded under HORIZON2020. The project is being coordinated by the University of Oslo, Norway and involves major research institutions across the EU. It is currently being carried out with the objective of developing a comprehensive regulatory framework for organoid research and organoid-related technologies. In the meantime, the European Parliament is working on legislation aimed at reducing the number of animal studies. The European Medicines Agency already recognized that organoids and organ-on-chip may become suitable alternatives to animal models during medicines development, in its wider effort to promote the 3R principles (replace, reduce and refine).

Further legal and ethical challenges to be addressed

The use of organoids and other MPS raises critical legal and ethical issues, which must be urgently addressed to allow their wide-spread utilization as part of pre-clinical studies within an acceptable framework.

In particular, since organoids are grown from human cells, initial donors rights must be respected and efficiently enforced. The original cells may come from foetal or adult tissues they may be pluripotent stem cells (PSCs), adult stem cells taken from specific tissues and reengineered somatic cells. Key challenges notably relate to the donors informed consent, (which issue has already been addressed by many scholars), research on human embryos and data protection issues. Complete anonymity of human tissue has been shown to be neither possible (due to the identifiable nature of DNA) nor desirable (as the data is necessary to validate prediction models). The donor must be able to control, to some extent, the subsequent use of his/her samples; in practice, consent may not be easily withdrawn (or with very limited effect) once organoids have been successfully developed and used in a pre-clinical study.

Strong quality standards should further be developed and complied with when it comes to producing organoids for pre-clinical purposes. Indeed, a set of specifications for the production of human 3D organoids used as medicines has been proposed. One could imagine specific guidelines applicable to the production of organoids for drug development purposes, to ensure consistent production methods as well as reliability as pre-clinical models. This calls for a wider systemic approach as to the regulation of human tissue and cells intended for human versus research application. On this point, it is interesting to note that a proposal for a regulation on standards of quality and safety for substances of human origin intended for human application is currently being examined in the EU, which expressly excludes their use in research that does not involve application to the human body.

Moreover, specific issues are triggered depending on the type of laboratory-cultivated model. For instance, the development of human cerebral organoids raises questions in terms of moral status and legal protection. Indeed, studies suggest that developed neuronal models show complex electrical activity the human cerebral organoids (sometimes referred to as mini-brains) can command a muscle connected thereto, be receptive to stimuli and may even exhibit a rudimentary form of consciousness. This raises questions as to the core definition of human being and, from a legal standpoint, personhood, the beginning and end of life, as well as the legal protection that should be awarded to such in vitro models (how they can be engineered, used, destroyed etc). In addition, the existence of sophisticated sentient models creates uncertainty regarding what moral status should be awarded to them. These issues are particularly complex as legal, ethical, philosophical, societal and political aspects are necessarily intertwined, and the way they are addressed may greatly vary from one jurisdiction to another.

Further legal and ethical challenges should be addressed in connection with the production and use of organoids beyond pre-clinical studies such as their potential patentability, their commercialization (while certain countries like France forbids the commercialization of human products and elements), their use for transplantation, the articulation with regulations on genome editing, chimeras and human cloning etc.

Conclusion

The rapid progress of scientific research around organoids and other MPS bears the potential to revolutionize many aspects of medical and pharmaceutical research. In particular, they hold great promise in the pursuit of a suitable (and potentially more reliable) alternative to the use of animal models in pre-clinical studies. Beyond this, legal and ethical challenges should be addressed in connection with the production and use of organoids in other applications such as their potential patentability, their commercialization (while certain countries like France forbids the commercialization of human products and elements), their use for transplantation, and the articulation with the regulations on genome editing, the creation of chimeras and human cloning.

Definitions:

Microphysiological systems (MPS): an umbrella term for organ-on-chip (OOC), organoids or tumoroids (stem cells grown in a dish).

Organ-on-a-chip (OOC): from the field of microfluidics, a multi-channel 3-D cell culture. An integrated circuit that simulates the activities, mechanics and physiological response of an entire organ or an organ system.

Organoid: means resembling an organ. Organoids are defined by three characteristics. The cells arrange themselves in vitro into three-dimensional organization that is characteristic for the organ in vivo, the resulting structure consists of multiple cells found in that particular organ and the cells execute at least some of the functions that they normally carry out in that organ.

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Organoids: science fiction or the future of pre-clinical studies? - Lexology

The stem cell industry has scored a major victory in its efforts to keep patient treatments exempt from Food and Drug Administration regulations, brushing aside the regulatory agencys concerns that the therapies are unproven and could be dangerous.

The FDA made that argument in 2018 when it sought court orders to stop the Beverly Hills and Rancho Mirage offices of the California Stem Cell Treatment Center from administering the treatments. The move was part of a yearslong FDA crackdown on clinics nationally claiming that stem cells can treat or cure conditions including orthopedic injuries, Alzheimers and Parkinsons diseases, multiple sclerosis, and erectile dysfunction.

Federal Judge Jesus G. Bernal of the U.S. District Court for the Central District of California oversaw a seven-day trial in May 2021 based on the FDAs lawsuit against CSCTC. More than a year later, on Sept. 1, Bernal issued a ruling siding with CSCTC. Bernal effectively rejected the FDA's argument that the clinics were selling unapproved drug products in the form of adipose cell mixtures, or connective tissue that is mainly composed of fat cells called adipocytes.

Industry attorneys say the FDA is likely to appeal the ruling by Bernal, who is based in Riverside, California, and was nominated to the federal bench in 2012 by then-President Barack Obama and confirmed by the Senate. But for now, it makes more difficult the agencys efforts to regulate some stem cell clinics. And it gives a green light to people seeking to use personal stem cells as part of medical treatments.

The FDAs lawsuits named as defenders CSCTCs founders, Dr. Elliot Lander and the late Dr. Mark Berman, who died in April. Lander said in a statement that Bernals ruling was a vindication of his companys scientific and medical bona fides.

We appreciate the Court's clear and unequivocal ruling, which affirms what we have been saying for 12 years: that our innovative surgical approach to personal cell therapy is safe and legal, Lander said. With this victory behind us, we look forward to refocusing our energy on our practice and harnessing life-changing stem cell treatments to support doctors and benefit patients across the country.

In a request for comment, a spokesperson for the regulatory agency said, The FDA is reviewing the courts decision and does not have further comment at this time.

Long-running battle

The FDA has long been skeptical of stem therapies. The agency also brought a similar suit against a Florida stem cell company. In 2015, at least three patients came forward stating they lost their eyesight after the material extracted by the Florida company, U.S. Stem Cell Clinic, was injected directly into their eyes to treat macular degeneration. The Florida clinic lost its suit in 2019, and its appeal request was subsequently denied.

In the case of CSCTC, the FDAs complaint said the treatments violated current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. The FDA argued that physician use of a patients own stem cells was equal to manufacturing a biological drug product that would, therefore, be subject to regulation.

CSCTC was founded in 2010 by Lander, a surgeon and board-certified urologist, and Berman, a board-certified otolaryngologist and cosmetic surgeon.

Berman returned from Japan in 2010 with technology that could isolate stem cells from a bodys fat from the bedside. After discovering the technology, Berman and Lander began to study the efficacy and safety of these cells. In 12 years, the team learned that stem cells are another source of repair cells, similar to bone marrow cells.

In 2012, the Cell Surgical Network, the research branch of CSCTC, was founded to teach these SVF technologies to qualified physicians across the globe who also sought to bring regenerative medicine into their own practices.

The approach quickly found adherents.

Laurie Hanna, an independent certified registered nurse anesthetist who worked previously with Berman, said stem cells relieved significant health problems.

I was living in pain with decreased quality of life. Over the course of 12 years, I was facing the prospect of a complete knee replacement and experienced a significant exacerbation of my chronic regional pain syndrome that was resistant to conventional medical treatment, Hanna told the Washington Examiner.

After surgery and chemotherapy for breast cancer, I developed lymphedema and chemo neuropathy. Through treatments with Cell Surgical Network, I was able to receive my own stem cells, Hanna said. My lymphedema significantly improved, neuropathy resolved, and quality of life was restored. Little did I know when I started personal cell therapy with CSN in 2010 that in 2022 stem cells would still be making me whole.

According to Lander, stem cell therapies are incredibly safe. They allow clinics to help patients by using their own bodies to heal in a way that is in harmony with nature, he added. Lander said that despite the intermission in treatments and research due to the suit, he and colleagues remain optimistic about the future of stem cell therapies.

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A win for stem cells | Washington Examiner

BOCA RATON, Fla., Sept. 14, 2022 /PRNewswire/ -- From breakthroughs in the prevention of post-concussion syndrome to unprecedented advances in post-stroke, traumatic brain injury and spinal cell regeneration, TransMedia Group will bring major media attention to Hyperbaric Oxygen Therapy (HBOT) and one of the fields' greatest pioneers, Veteran Hall of Famer Raymond Cralle.

"With HBOT, patients breathe pure oxygen in a pressurized chamber, helping injured or damaged cells begin to replicate, ultimately creating new, non-injured cells," said TransMedia Group President, Adrienne Mazzone. "Our PR campaign will highlight the outcomes from Cralle's groundbreaking studies of brain and spine injured veterans, and the staggering outcomes. We will educate the media on HBOT's powerful anti-inflammatory effects, including Cralle's protocols which have broken science barriers and are proven to grow new healthy stem cells."

To further build credibility and awareness, TransMedia Group will highlight many of the prestigious recognitions Cralle has received from top neurologists around the world, including the Hyperbaric Medicine Symposium, support from Florida Senator Tom Wright resulting in a Bill through the Florida Legislature and pro-bono care for countless veterans garnering his induction into the Florida Veterans Hall of Fame.

"We believe that HBOT will be more widely practiced as the public learns of its effectiveness," says Raymond Cralle, Founder of Oxygen Rescue Care Centers of America (ORCCA). "That's why TransMedia Group will help simplify the science while also giving reporters and editors our clients' incredible testimonials and home footage- bringing concrete success stories out of the medical journals and into life."

Mazzone says, "'Before' and 'After' Brain Scans are some of the most compelling pitch materials, along with the research that clearly shows how HBOT can sharply decrease veteran suicide rates, diminish the effects of PTSD, including less anger, sleep deprivation and mental anguish."

"We are excited to offer in-depth interviews spotlighting veterans, elite athletes, stroke patients, anti-aging enthusiasts and families who have had their lives changed at Cralle's outpatient neuropathic hyperbaric center in Delray Beach, Florida," said Mazzone. Cralle and his 501 C.3. Hope Springs are at the start of new horizons for HBOT.

TransMedia Group is an international public relations firm serving clients worldwide since 1981. One of its core niches is healthcare and wellness.

Media Contact:Adrienne Mazzone amazzone@transmediagroup.com 561-908-1683

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According to the American Cancer Society, Non-Hodgkin's lymphoma is one of the most common types of cancer, especially in children and young adults. "About 80,470 people (44,120 males and 36,350 females) will be diagnosed with NHL. This includes both adults and children. About 20,250 people will die from this cancer (11,700males and 8,550 females)." In addition, the site states, "Overall, the chance that a man will develop NHL in his lifetime is about 1 in 42; for a woman, the risk is about 1 in 52." Eat This, Not That! Health spoke with Dr. George Nahas, medical oncologist at Miami Cancer Institute, part of Baptist Health South Florida, specializing in the treatment of blood disorders and diseases who shares what to know about Non-Hodgkin's lymphoma. As always, please consult with your physician for medical advice. Read onand to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.

Dr. Nahas tells us, "There is a lot to know about Non-Hodgkin's Lymphoma that far exceeds the scope of a few thoughts! Non-Hodgkin's Lymphoma is a type of blood cancer that involves the lymph nodes, which is an important part of our immune system when acting normally. Unfortunately, when cells of a lymph node become cancerous, they form lymphoma."

Dr. Nahas says, "Non-Hodgkin's lymphoma is very treatable, when treatment is needed. There are many different types of lymphoma that span the spectrum between slower growing lymphomas to very aggressive, fast growing lymphomas. Treatment, therefore, spans from no treatment at all ("watchful waiting") all the way to chemotherapy and in some cases cellular therapy such as stem cell transplant."

The American Cancer Society lists several risk factors including age, gender, ethnicity, family history, exposure to certain chemicals, radiation exposure, a weakened immune system, certain autoimmune diseases, certain infections, weight and breast implants.

Dr. Nahas adds, "While there are a few factors that put patients at risk for lymphoma, there have not been definitive causes of lymphoma. For example, it is well known that HIV is associated with a lymphoma risk, however every patient with HIV does not develop lymphoma. This is currently a subject area that is constantly developing and warrants future exploration."

Dr. Nahas explains, "Every patient with suspicion of lymphoma is asked 3 questions. Do you have fevers? Do you have drenching night sweats? Have you had significant weight loss over the past 3 months? In lymphoma, these are referred to as B symptoms and are actually part of the staging algorithm. It should be noted, however, that these symptoms do not necessarily mean that a patient has lymphoma, but warrants further testing such as imaging, blood work, and tissue biopsy."6254a4d1642c605c54bf1cab17d50f1e

According to the American Cancer Society, "The most common symptom of HL is a lump in the neck, under the arm, or in the groin, which is an enlarged lymph node. It doesn't usually hurt, but it may become painful after drinking alcohol. The lump might get bigger over time, or new lumps might appear near it or even in other parts of the body. Still, HL is not the most common cause of lymph node swelling. Most enlarged lymph nodes, especially in children, are caused by an infection. Lymph nodes that grow because of infection are called reactive or hyperplastic nodes. These often hurt when they're touched. If an infection is the cause, the node should go back to its normal size after the infection goes away. Other cancers can cause swollen lymph nodes, too. If you have an enlarged lymph node, especially if you haven't had a recent infection, it's best to see a doctor so that the cause can be found and treated, if needed."

The Mayo Clinic lists the following symptoms:

Heather Newgen

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Sure Signs You Have Non-Hodgkin's Lymphoma Eat This Not That - Eat This, Not That

Ten percent of all diagnosed cancers in the United States are blood cancers, and they can be deadly. There are exciting new treatments and research happening in Baltimore that are giving patients hope."These therapies cure the patients that have no other treatment options. It's been a remarkable breakthrough," said Dr. Aaron Rapoport, of the University of Maryland School of Medicine.Cutting-edge technology will treat many types of cancers such as leukemia, lymphoma and myeloma. Traditional treatments include chemotherapy, radiation and stem cell therapy, but what if those treatments don't work?Now, there is an immunotherapy for aggressive blood cancers that is seeing remarkable results.Chip Baldwin, who has a big laugh and immense love for his grandchildren, thought it was the end when he was told in January 2018 that chemotherapy was no longer working to treat his lymphoma."This is Kyle, he's about 3 1/2 years old and he lives in Florida. (My) granddaughter Maple. She and her family live in Fells Point. And this is (my) granddaughter Rosemary and she's a doll, and they call me Pop-pop," Baldwin said.But Baldwin almost never met two of his grandchildren.Baldwin said he had difficulty "leaving (his wife), Angela, and leaving the family, trying to figure out how they're going to get by."He was out of options, or so he thought. Not willing to give up, his wife, Angela Baldwin, began researching and came across a promising new treatment."(It was) probably the last treatment that I could have received. Had I not received it and had it not been positive to put me in remission, I probably wouldn't be talking to you today," Baldwin said.The treatment he received had just been approved by the U.S. Food and Drug Administration months earlier. It's called "CAR T-cell Therapy," and it uses the patient's own, re-engineered immune cells to kill cancer. Rapoport helped pioneer the development of CAR T-cell at the University of Maryland Greenebaum Comprehensive Cancer Center. Baldwin was just the second patient to receive it."The notion that one could perhaps harness the immune system, or educate the immune system, to better protect us from cancer, but also to recognize and fight against cancer, has been a goal for decades, centuries really," Rapoport said.It appears that goal has been reached. Here's how it works: The medical team extracts immune cells, called T-cells, out of the patient's blood. The cells are sent to a special lab in California, where scientists change the cells' DNA to put receptors on them called "CAR" - Chimeric Antigen Receptors. They enable the immune cells to recognize, hunt down and kill the cancer cells. The California lab then sends the now-re-engineered immune cells back to the Greenebaum Comprehensive Cancer Center."These are CAR T-cells growing in the flask here. These are CAR T-cells that were made in the lab," said Dr. Djordje Atanackovic, a hematology oncologist at the University of Maryland Medical Center.Under a microscope, spots on a cancer cell can be seen that are the killer CAR T-cells. "You could use these right now to treat a patient," Atanackovic said.For the final step, patients are admitted to the hospital and the medical team puts the T-cells back into the patient, where the cells multiply by the millions and destroy the cancer. For Baldwin, that was the day after Easter 2018."Then, about four months later, they determined that all the cancer cells had died, " Baldwin said."Being told that their scans are negative is a really overwhelming experience -- not just for the patients, but for the families and also the nurses and physicians, the team members that are involved in their care," Rapoport said.When looking at CT scan images of two other lymphoma patients, black areas seen on one of the images is extensive cancer. The other image shows the same patient after CAR T-cell therapy, and the cancer is gone. Right now, CAR T-cell Therapy is approved to treat aggressive blood cancers Lymphoma, B-cell Leukemia and Myeloma. But Atanackovic believes that's just the beginning."I'm pretty optimistic that, in 10 years from now, we'll have novel immunotherapies that we can't even imagine at this point for everyone, or at least most of our patients with cancer," Atanackovic said.Four years after his treatment, Baldwin is still in remission. He doesn't like the word "cure" because he's afraid it's bad luck. The word Baldwin keeps saying is: "'Unbelievable.' And even to this day, I kind of can't believe I'm in remission and I'm able to live my life. Since then, I've had two grandchildren and it's been wonderful. Had it not been for the university and the treatment, I would never have seen the two kids."So far, 250 patients have been treated with CAR T-cell Therapy at the University of Maryland, but it's not perfect and researchers are still working to improve it. The success rate for patients with aggressive lymphoma, for example, is 50% and some patients have side effects, like flu-like symptoms, so they typically stay in the hospital for days or even weeks.Many may wonder whether this is covered by insurance. The answer is yes. Keep in mind, right now, it is approved by FDA as a second-line therapy, so patients have to try a different treatment first. But, immunotherapy like CAR-T is the future of cancer treatment.

Ten percent of all diagnosed cancers in the United States are blood cancers, and they can be deadly. There are exciting new treatments and research happening in Baltimore that are giving patients hope.

"These therapies cure the patients that have no other treatment options. It's been a remarkable breakthrough," said Dr. Aaron Rapoport, of the University of Maryland School of Medicine.

Cutting-edge technology will treat many types of cancers such as leukemia, lymphoma and myeloma. Traditional treatments include chemotherapy, radiation and stem cell therapy, but what if those treatments don't work?

Now, there is an immunotherapy for aggressive blood cancers that is seeing remarkable results.

Chip Baldwin, who has a big laugh and immense love for his grandchildren, thought it was the end when he was told in January 2018 that chemotherapy was no longer working to treat his lymphoma.

"This is Kyle, he's about 3 1/2 years old and he lives in Florida. (My) granddaughter Maple. She and her family live in Fells Point. And this is (my) granddaughter Rosemary and she's a doll, and they call me Pop-pop," Baldwin said.

But Baldwin almost never met two of his grandchildren.

Baldwin said he had difficulty "leaving (his wife), Angela, and leaving the family, trying to figure out how they're going to get by."

He was out of options, or so he thought. Not willing to give up, his wife, Angela Baldwin, began researching and came across a promising new treatment.

"(It was) probably the last treatment that I could have received. Had I not received it and had it not been positive to put me in remission, I probably wouldn't be talking to you today," Baldwin said.

The treatment he received had just been approved by the U.S. Food and Drug Administration months earlier. It's called "CAR T-cell Therapy," and it uses the patient's own, re-engineered immune cells to kill cancer.

Rapoport helped pioneer the development of CAR T-cell at the University of Maryland Greenebaum Comprehensive Cancer Center. Baldwin was just the second patient to receive it.

"The notion that one could perhaps harness the immune system, or educate the immune system, to better protect us from cancer, but also to recognize and fight against cancer, has been a goal for decades, centuries really," Rapoport said.

It appears that goal has been reached. Here's how it works: The medical team extracts immune cells, called T-cells, out of the patient's blood. The cells are sent to a special lab in California, where scientists change the cells' DNA to put receptors on them called "CAR" - Chimeric Antigen Receptors. They enable the immune cells to recognize, hunt down and kill the cancer cells. The California lab then sends the now-re-engineered immune cells back to the Greenebaum Comprehensive Cancer Center.

"These are CAR T-cells growing in the flask here. These are CAR T-cells that were made in the lab," said Dr. Djordje Atanackovic, a hematology oncologist at the University of Maryland Medical Center.

Under a microscope, spots on a cancer cell can be seen that are the killer CAR T-cells.

"You could use these right now to treat a patient," Atanackovic said.

For the final step, patients are admitted to the hospital and the medical team puts the T-cells back into the patient, where the cells multiply by the millions and destroy the cancer.

For Baldwin, that was the day after Easter 2018.

"Then, about four months later, they determined that all the cancer cells had died, " Baldwin said.

"Being told that their scans are negative is a really overwhelming experience -- not just for the patients, but for the families and also the nurses and physicians, the team members that are involved in their care," Rapoport said.

When looking at CT scan images of two other lymphoma patients, black areas seen on one of the images is extensive cancer. The other image shows the same patient after CAR T-cell therapy, and the cancer is gone.

Right now, CAR T-cell Therapy is approved to treat aggressive blood cancers Lymphoma, B-cell Leukemia and Myeloma. But Atanackovic believes that's just the beginning.

"I'm pretty optimistic that, in 10 years from now, we'll have novel immunotherapies that we can't even imagine at this point for everyone, or at least most of our patients with cancer," Atanackovic said.

Four years after his treatment, Baldwin is still in remission. He doesn't like the word "cure" because he's afraid it's bad luck.

The word Baldwin keeps saying is: "'Unbelievable.' And even to this day, I kind of can't believe I'm in remission and I'm able to live my life. Since then, I've had two grandchildren and it's been wonderful. Had it not been for the university and the treatment, I would never have seen the two kids."

So far, 250 patients have been treated with CAR T-cell Therapy at the University of Maryland, but it's not perfect and researchers are still working to improve it. The success rate for patients with aggressive lymphoma, for example, is 50% and some patients have side effects, like flu-like symptoms, so they typically stay in the hospital for days or even weeks.

Many may wonder whether this is covered by insurance. The answer is yes. Keep in mind, right now, it is approved by FDA as a second-line therapy, so patients have to try a different treatment first. But, immunotherapy like CAR-T is the future of cancer treatment.

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New treatment changing outlook for those with blood cancers - WBAL TV Baltimore

Seven University of Central Florida graduate students are currently interning at Adobe and 3M, among other leading employers thanks to fellowships supported by the National Graduate Degrees for Minorities in Engineering Fellowship (GEM) program.

The GEM program began in 1976. The public-private partnership aims to connect students from underrepresented groups with the nations top employers and universities. Those selected receive a $16,000 fellowship from the GEM Consortium, a paid summer internship, and a tuition remission for a masters or doctoral program of their choice. The national program is highly competitive and enables students to be placed in coveted internships with some of the nations industry leaders in STEM.

UCF has been a partner university for more than 20 years. The GEM program is one of several supporting students of color at UCF, a Hispanic Serving Institution.

This years UCF GEM Fellows are:

Novia Berriel 21MS

Currently a researcher in associate professor of materials science Parag Banerjees lab, Novia Berriel will continue her education as a doctoral fellow in materials science. She originally came to UCF because of the so-called two-body problem the need for two professional spouses to find suitable placements in the same area but has since fallen in love with everything the university has to offer.

UCF is at the cutting edge of everything, she says. And being a Hispanic woman, I appreciate that its an HSI.

Berriel earned her masters in physics at UCF in 2021. Since she began the degree in 2018, she has been working to explore atomic layer deposition of thin films. In this capacity, shes been able to engage with different disciplines by producing the films needed for a variety of devices.

The opportunity to be interdisciplinary in your everyday life is one of her favorite aspects of the materials science department at UCF.

You can collaboratively interface with so many other labs, Berriel says. I work in Research Building I, which houses faculty and labs from many different departments. So, Ive been able to meet experts in different disciplines by just walking around.

As a GEM fellow and intern for Lam Research, she hopes to build expertise in semiconductor development and solar cells, while making the most of the chance to research freely, meet other Fellows and embrace interdisciplinary collaboration.

Jeffrey Chan-Santiago

Drawn to UCFs state-of-the-art research at the intersection of computer vision, machine learning and robotics, Jeffrey Chan-Santiago knew it would be the best place to earn his doctorate in computer science.

He already has experience applying self-supervised models to monitor and identify honeybees in their natural habitat, modify architectural plans and more through work he conducts at the University of Puerto Rico, Ro Piedras. He earned a bachelors degree in computer science from the university and is currently completing his masters degree in applied mathematics.

He is also an intern at Raytheon for the summer. There and at UCF, he hopes to enable robots to learn more efficiently and safely.

He says he is grateful to be at one of the first steps of a lifelong career in research, and he plans to become a professor, ideally in Puerto Rico, and help motivate students toward research careers in STEM.

Joseph Green

As a GEM fellow at UCF and an intern for Adobe, Joseph Green hopes to broaden his every horizon.

He received his bachelors degree in computer science in 2020 at Auburn University, and says he is eager to make the transition to highly populated Orlando, which has attractions like Walt Disney World.

Green credits his participation in the GEM Fellowship program to encouragement he received as part of a learning community at Auburn. He says he looks forward to joining similarly supportive communities at UCF. This will be his first time living in an area he doesnt know, but Green says he already knows he will have a great time experiencing a new schools culture.

In the process, he says he will be able to see all the variety his field has to offer.

During his masters program in computer science, he plans to make the most of the opportunity to pursue machine learning, complex networks and other inspiring topics.

Dania Jean-Baptiste

Earning her bachelors degree with honors in computer information systems from Bethune-Cookman University in 2021 made Dania Jean-Baptiste realize how much she enjoyed her field and how much she had left to learn.

To ensure her work would remain at the cutting edge of security standards, Baptiste decided to pursue a masters degree in cybersecurity and privacy. She initially enrolled at Florida A&M University; however, she decided to transfer to another university. Although the transition was difficult, she says having faith helped her continue her path.

So, she applied and was admitted to be a GEM Fellow at UCF. Her fellowship is sponsored by Intel. And this summer, Baptiste is participating in Tech Forward a Salesforce training program that prepares participants from underrepresented groups to earn their certification in network administration.

Baptiste says she looks forward to enriching experiences in research. Her ultimate goal is to learn as much as she can about data analytics, artificial intelligence and cloud computing. Then, she will be able to put her skills to use while giving back to her community.

Andrea Molina Moreno 22 After building a foundation in the different areas of STEM, Andrea Molina Moreno decided to focus on materials engineering.

She says that it has a uniquely broad scope. You can work with anything you choose, since almost everything is material.

Moreno came upon this decision in the midst of several transitions: immigrating from Caracas, Venezuela, transferring from Simn Bolvar University, and graduating among UCFs first cohort of bachelors materials science students.

With the GEM fellowship, she will pursue a doctoral degree in materials science. This summer, she is gaining experience in industry by interning at 3M in Minneapolis. As she continues her education, Moreno most looks forward to serving as a role model for fellow Hispanic female engineers.

What has motivated her so far is the desire to gather as much knowledge as she possibly can. She shares that Ive been studying for so much of my life, and its what I really enjoy doing learning more and more.

Jason Ortiz

The COVID-19 pandemic gave Jason Ortiz an opportunity to pause and think back to some of his original passions.

In 2021, he had already spent three years working as a software engineer at Microsoft in Seattle, where he enjoyed the opportunity to tackle exciting problems in cloud-computing. Still, he had always hoped to further explore 3D applications. Extended reality (XR) encompassing the spectrum of virtual, mixed and augmented reality applications particularly stood out to him.

He says he realized that the fields potential is outstanding. It can address a lot of problems related to isolation, by helping people work in novel ways while still feeling a sense of togetherness. So, he did a bit of research in his downtime.

Thats when Ortiz discovered the pioneering work of UCF Engineering Professor Carolina Cruz-Neira. Even better, Cruz-Neira was teaching in Orlando, his hometown. The GEM Fellowship offered a way to return for his doctorate.

He jumped at the chance. Currently an intern at Argonne National Laboratory, Ortiz will begin as a student at UCF in the fall. He most looks forward to conducting innovative research on collaborative XR and building the teaching skills he began developing as an undergraduate teaching assistant. He is also eager to be the first in his family with a doctorate and hopes to encourage fellow Puerto Ricans to pursue higher education.

Kiaria Tucker

After years of watching crime shows and pointing out technicians as the real heroes, Kiaria Tucker found it easy to decide on a career path.

She remembers that the detectives never actually held my interest. The technicians were the ones who could say This is what happened. This is what the evidence shows. Its thanks to the technicians that they had the evidence they needed to do anything.

Forensic science offered the opportunity for excitement and a tangible impact. So, Tucker received her bachelors degree in chemistry with a forensic concentration from Talladega College. While there, she participated in the McNair Scholars Program, where a mentor encouraged her to apply to the GEM fellowship.

Since her acceptance, Tucker has explored microbiological chemistry research as an intern for Oak Ridge National Laboratory in Knoxville, Tennessee. This fall, she will begin as a thesis-seeking doctoral student in chemistry at UCF. Tucker says she looks forward to earning the skills and certifications that will make her a valuable member of a forensic team. She says from everything shes seen so far, the field still never fails to excite her.

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Engineering Graduate Fellows Get Hands-on Experience with National Industry Leaders - UCF

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Australian biotech Skin2Neuron Pty Ltd. (S2N) has what no one has to date - reversal of a dementia-like syndrome in a natural animal form of Alzheimer's disease.

SYDNEY, June 21, 2022 (GLOBE NEWSWIRE) -- With the once dominant amyloid hypothesis of Alzheimer's disease suffering yet another crushing blow this week, the field is desperate for a ray of hope. Enter S2N, a new Australian biotech pioneering an all-new neurorestorative approach, aiming to rebuild and replace the lost brain cells in Alzheimer's that underlies clinical symptoms.

In a world first, a veterinary trial led by S2N suggests the audacious concept may work. S2N's new form of cell therapy reversed the dementia-like syndrome that strikes down many older pet dogs with Alzheimer's.

Co-founder Professor Michael Valenzuela explains, "Because of deep parallels between the canine brain and human brain, and canine Alzheimer's and human Alzheimer's, I started this trial 10 years ago with the assumption that if it's going to work in humans, then it needs to work in dogs first. And the results exceeded my wildest expectations."

Dementia was reversed in more than half of the canine patients, with a clinically meaningful improvement in 80%. For many of the carers, it was a life-changing turnaround, some at the point of considering euthanasia before treatment.

Fiona Gibbs, carer of Leo, a 12-yo Pomeranian in the trial, describes the impact: "Before treatment, Leo was really bad, forgetting who we were, getting lost, and having these unpredictable episodes where he would growl and snap - it was really scary and we just couldn't go on. A few months after treatment, he started getting better, and then he was back to his normal self, and we look back at the movies and think, 'Wow, was he really that bad?'"

Leo's life-changing improvement lasted almost two years, typical of clinical recovery in the trial.

And when Valenzuela looked in the brain, the findings were remarkable, "The hippocampus, the memory centre of the brain, was packed with baby neurons and new synapses, precisely where we delivered the cells. Compared to untreated dogs, it was like night and day".

Importantly, microscopic analysis confirmed the dogs had classic Alzheimer pathology. In other words, the cell therapy worked in the setting of natural disease, a first of its kind.

"Given our doggie patients also had many of the same health issues that older people face, it gives me even greater confidence," says Valenzuela.

Stem cell pioneer Professor Brent Reynolds of the University of Florida, not connected to the study, considers it a landmark in the quest to treat brain degeneration. "Alzheimer's is an area of medicine that needs new thinking. What stands out are clinically meaningful outcomes in a natural canine model of this devastating disease. Also, the company's approach to generating cells from the same patient could solve many of the problems facingcell therapies."

The study helps pave the way for S2N to launch a world-first human trial in 2024.

Contact

Professor Michael Valenzuela

Co-founder & CEO, Skin2Neuron Pty Ltd.

[emailprotected]

+61 413 603 784 (AEST)

Related Images

Image 1: Figure 1/2

Hippocampus (memory centre) of an older dog with dementia-like syndrome successfully treated with S2N's cells. It is packed with green cells that are new neurons (brain cells) and yellow dots, new synapses (connections between brain cells).

Image 2: Figure 2/2

Same brain area in an aged untreated dog. There are no new neurons (no green cells), a few red dots (old synapses), but no new synapses (no yellow dots).

This content was issued through the press release distribution service at Newswire.com.

Originally posted here:
New Alzheimer's Treatment on Horizon as Dementia Reversed for First Time in Dogs - StreetInsider.com

Life Cycle of a Moss - Infographic

Mosses alternate between diploid and haploid generations in their life cycle, which is unique among flowering plants. Where does fertilization take place in the moss life cycle? Are spores haploid or diploid? Scroll to the Key Takeaways to get the answers, or start from the top to learn about the moss life cycle.

How does a moss reproduce?

Mosses have two forms of reproduction: sexual reproduction and asexual/ vegetative reproduction. This is true for all bryophytes.

Practically all flowering plants are diploid, but for mosses, this is different. Mosses alternate between diploid generations (as sporophytes) and haploid generations (as gametophytes).

Generally speaking, sexual reproduction is the process where genes from two different parents mix to produce offspring with a genetic makeup similar to, but different from, each parent.

The sexual reproduction of the moss (bryophyte) life cycle alternates between diploid sporophyte and haploid gametophyte phases. In a nutshell, haploid gametophytes produce haploid gametes, which can be sperm or eggs. When egg and sperm merge, they form a diploid zygote which grows into a diploid sporophyte. Sporophytes produce haploid spores, containing genetic information from both haploid gametophyte parents. A spore gives rise to a haploid gametophyte, completing the cycle.

A single gametophyte moss plant can produce both sperm and eggs. This can occur on different parts of the same plant, one part producing sperm and another part producing eggs. However, a plant usually produces either all sperm-producing organs or all egg-producing organs at any one time. This way it doesn't breed with itself, promoting genetic variation. The female structure for producing eggs is known as the archegonium, and the male structure for producing sperm is known as the antheridium. Antheridia are tiny, typically stalked, club-shaped or spherical structures. Archegonia are bottle-like containers, their wall just one cell thick. Archegonia are typically formed in groups. Archegonia and antheridia are usually bundled in leaf rosettes similar to flowers, called perichaetia. Elongated club-shaped cell filaments called Paraphyse are sometimes found on the gametophyte, storing water and protecting the archegonia sand antheridia from drying up.

When the antheridia are ripe and the flower gets wet from rain, numerous antherozoids (spermatozoids / sperm cells), are released. Antherozoids are only able to move underwater. They swim using two threadlike tails. Some successfully end up on female gametophyte moss plants and are chemically attracted to the archegonium. Each archegonium holds one egg, in a swollen section called the venter. The sperm enter the archegonium through the narrow channel in its neck. Fertilization occurs in the archegonium to form a diploid zygote. Once one archegonium in a group has been fertilized, in many cases the others lose the ability to be fertilized. This is caused by an inhibitory hormone released from the fertilized archegonium.

The formation of the zygote begins the second phase of the moss life cycle, where the zygote develops into a diploid sporophyte (spore-plant).

After fertilization, the archegonium on the gametophyte plant becomes modified into a protective sheath around the young sporophyte. The sporophyte begins to grow by mitosis (diploid cell division) out of the top of the archegonium. It elongates and after a few cell divisions begins differentiation. At this point the sporophyte is practically a parasite on the gametophyte plant, although it may produce some food of its own via photosynthesis in the early stages of growth.

The embryonic sporophyte consists of three structures: a foot, seta, and a capsule. The foot, on the lower portion, anchors the sporophyte to the gametophyte via penetration and helps to transfer water and nutrients from the gametophyte. The seta is a long erect supporting stalk. At the end of the sporophyte is a pod-like capsule where spores are produced. The seta only occurs in species where the mature capsule is stalked.

Transfer cells develop at the sporophyte-gametophyte boundary in the majority of bryophytes, but not all. These specialized cells allow efficient transfer of nutrients from the gametophyte to the sporophyte. They may form on the gametophyte, sporophyte, or both. The gametophyte-sporophyte junction is often convoluted and maze-like. This increases the surface area, allowing for more transfer cells than a simple boundary, thus increasing the rate at which nutrients can flow to the sporophyte.

A capsule may contain four to over a million spores, depending on the species. It also may be stalked or stalkless depending on the species. In most mosses, the mouth of the capsule is covered by a lid-like operculum, which falls off when the spores are mature. A membranous hood, the calyptra, which is also discarded at maturity, further protects the operculum.

In wet conditions the spores can't travel very far. A tiny tooth-like structure around the mouth of the capsule controls the release of the spores. These structures, called the peristome, consist of one or two rows of teeth. They prevent the release of the spores during wet conditions by remaining closed. In dry conditions they open, releasing the spores.

Each spore contains a mix of genes from the two parents. If the spore falls onto a damp area of ground, it may germinate into a branching, threadlike filamentous protonema. Cusps bud from the protonema then grow into leafy male or female gametophytes, completing the life cycle.

In addition to sexual reproduction, mosses can reproduce asexually (vegetatively). The method they use to accomplish this depends on the situation they're in.

When the stem of a large clump of moss dies back, the stem-less clump becomes individual plants.

When bits of the stem or even a single leaf from the moss plant are broken off, these bits can then regenerate to form a new plant.

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Larry's contributions are featured by TEDx, Fast Company, and Gizmodo Japan, and cited in books by Routledge and No Starch Press. His stories and opinions are in magazines and newspapers including Slate, Vox, Toronto Star, Orlando Sentinel, and Vancouver Sun.He is a Harvard Medical School incoming Master's student, a Florida State University "Notable Nole," and has served as an invited speaker at Harvard, FSU, and USF.He illustrates the sciences for a more just and sustainable world.

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Life Cycle of a Moss - Infographic - STEM Lounge

Long COVID-19 syndrome, in which symptoms last a year or longer beyond infection, impacts about 30 percent of survivors of the coronavirus. It is a multifaceted systemic condition characterized by fatigue, cognitive fog, and often heart, lung and neurological complications.

Lina Shehadeh, Ph.D., professor of medicine in the Interdisciplinary Stem Cell Institute and Division of Cardiology at the University of Miami Miller School of Medicine, received a $1 million grant from the American Heart Association to study long COVID. Recognizing the substantial public health impact and burden of this syndrome, the American Heart Association awarded three-year grants to 10 research programs in the nation with proposals for unraveling long COVIDs etiology and molecular mechanisms.

(l-r) Dr. Leo Tamariz, Dr. Shathiyah Kulandavelu, Dr. Lina Shehadeh, and Dr. Jose Condor

When you have an impact that is systemic not confined to certain organs you think about the circulatory system, since its function affects everything else, Dr. Shehadeh said. We have observed signs that the endothelial function of the blood vessels is abnormal in preclinical models of long COVID. Now, we are working to connect the dots and explain this cascade.

As part of her research, Dr. Shehadeh is using a mouse model and human blood samples to interrogate a chain of events that may account for symptoms seen in people with long COVID. This chain begins with virus-induced lung inflammation and defective cholesterol homeostasis, and ultimately leads to endothelial dysfunction.

The team is investigating evidence that there is an overzealous inflammatory response from the mating of protein spikes on the SARS-CoV-2 virus with low-density lipoprotein receptors (LDLr) on the infected cells. Central to this response is the formation of neutrophil extracellular traps (NETs), which are net-like structures composed of DNA-histone complexes and proteins. These form as the immune system activates an overabundance of neutrophils in the lungs.

While they form as an overreaction to real pathogens like the SARS-CoV-2 virus, they are also complicit in a number of autoimmune diseases, coagulation disorders and thrombus, diabetes, atherosclerosis, vasculitis, sepsis and cancer.

In COVID-19, when these neutrophils are overwhelmed or defeated by the virus, they burst in the lungs, releasing their DNA material [netosis], Dr. Shehadeh explained. From there we think the NETs are carried through the systemic circulation and become stuck and then embedded in the vessel walls in the limbs and in the organs. This would explain the loss of normal homeostasis in the vascular walls and the tendency toward thrombus we see so often in COVID long-haulers.

Dr. Shehadeh is working with Jeffrey Goldberger, M.D., M.B.A., professor of medicine and chief of the Cardiovascular Division, and Leonardo J. Tamariz, M.D., an internist in the COVID-19 Long-haulers Clinic at the Miami Veterans Affairs Healthcare System. Dr. Tamariz is obtaining blood samples and heart and lung MRI images of 150 or so patients from the clinic to sample the neutrophils and check for markers of netosis, while Dr. Goldberger is examining the MRIs and other cardiac readouts to assess visible vessel anomalies.

This ties in with work we have done for years in studying battle fatigue in veterans, which can persist long after they return from the field, Dr. Tamariz said.

Other key team members are Shathiyah Kulandavelu, Ph.D., a junior faculty member at the Interdisciplinary Stem Cell Institute whose expertise is in endothelial function, and Jose Manuel Condor Capcha, Ph.D, a postdoctoral associate who is spearheading the lab work.

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Miller School Researchers on the Trail to Unraveling Long COVID-19 - Florida Hospital News and Healthcare Report - South Florida Hospital News