Aileron Therapeutics Announces Late-Breaking Oral Presentation of Non-Clinical Data Demonstrating ALRN-6924 Protected Human Hair Follicles and Their…
By daniellenierenberg
Aileron Therapeutics, Inc.
Taxanes, such as paclitaxel and docetaxel, cause severe and often permanent chemotherapy-induced hair loss (alopecia)
New non-clinical data demonstrate proof of principle that ALRN-6924 can temporarily arrest the cell cycle in human scalp hair follicles and their stem cells
ALRN-6924-induced cell cycle arrest protected hair follicles from paclitaxel-induced toxicity and irreversible stem cell damage
Ailerons precision medicine-based approach is designed to selectively protect normal, healthy cells from chemotherapy while ensuring chemotherapy cannot protect cancer cells
Ailerons ongoing non-small cell lung cancer (NSCLC) clinical trial and upcoming breast cancer clinical trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities and other side effects, including alopecia
BOSTON, May 10, 2022 (GLOBE NEWSWIRE) -- Aileron Therapeutics (Nasdaq: ALRN), a chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives, today announced a late-breaking oral presentation at the upcoming Society for Investigative Dermatology (SID) Annual Meeting, which will be held May 18 21, 2022 in Portland, Oregon. The presentation will highlight new non-clinical data developed in collaboration with Professor Ralf Paus, M.D., DSc, FRSB and his colleagues at the Dr. Phillip Frost Department of Dermatology & Cutaneous Surgery at the University of Miami Miller School of Medicine. This collaboration has generated promising ex vivo data demonstrating that ALRN-6924 protected human hair follicles and their stem cells from chemotherapy-induced acute and permanent damage. Details of the presentation are as follows:
Title:
ALRN-6924, a dual inhibitor of MDMX and MDM2, protects human scalp hair follicles and their epithelial stem cells from paclitaxel-induced toxicity (LB1018)
Presenter:
Jennifer Gherardini, Ph.D.; Paus Laboratory, University of Miami Miller School of Medicine
Date:
Thursday, May 19th
Time:
8:45 AM 11:15 AM PT
Session:
Late-Breaking Abstract Concurrent Session
Chemotherapy-induced toxicities range from severe and life-threatening to those that impact and diminish patients quality of life, sometimes long after chemotherapy has been completed. These toxicities occur because chemotherapy destroys normal, healthy cells while simultaneously destroying cancer cells, said Manuel Aivado, M.D., Ph.D., President and Chief Executive Officer at Aileron. Previously, we showed chemoprotection against severe bone marrow toxicities in small cell lung cancer patients receiving topotecan and demonstrated in healthy volunteers the mechanism of action cell cycle arrest underlying this chemoprotection benefit. We are excited to now present new data that may suggest ALRN-6924s ability to also protect against chemotherapy-induced hair loss, another devastating chemotherapy-induced side effect for millions of cancer patients.
Dr. Paus commented, These results got us quite excited as they directly follow in the footsteps of our prior work that showed arresting the cell cycle can have a strong protective effect against taxane-induced hair follicle damage. Until our research with ALRN-6924, we had not come across a cell cycle arrest-inducing drug that is in clinical testing for protection of normal cells without protecting cancer cells. Thus, ALRN-6924 invites a very promising and completely novel selective protection approach. In addition, we found that ALRN-6924 may exert some additional benefits that could reduce the risk of long-term damage of human hair follicle stem cells by taxanes.
Story continues
Aileron is currently developing ALRN-6924, a first-in-class MDM2/MDMX dual inhibitor, to selectively protect healthy cells in patients with cancers that harbor p53 mutations to reduce or eliminate chemotherapy-induced side effects while preserving chemotherapys attack on cancer cells. ALRN-6924 is designed to activate p53 in normal cells, which in turn upregulates p21, which pauses cell cycle in normal cells but not in p53-mutated cancer cells. The companys vision is to bring chemoprotection to all patients with p53-mutated cancer regardless of the type of cancer or chemotherapy.
About the Findings
Taxanes, such as paclitaxel and docetaxel, are known to cause severe and often permanent chemotherapy-induced alopecia. Over 90% of patients treated with this chemotherapy class experience alopecia, and approximately 10% (paclitaxel) to 25% (docetaxel) of patients experience permanent alopecia. Dr. Paus and his team previously demonstrated that paclitaxel damages human scalp hair follicles by inducing massive mitotic defects and apoptosis in hair matrix keratinocytes as well as bulge stem cell DNA damage, and that pharmacological induction of transient cell cycle arrest can protect hair follicles and stem cells (Purba et al. EMBO Molecular Medicine 2019). Aileron previously conducted in vitro studies showing that ALRN-6924 protected human fibroblasts in cell culture from multiple chemotherapies, but not p53-mutant breast cancer cells.
In the new non-clinical findings to be presented at the SID meeting, when organ-cultured anagen (i.e., active growth phase) scalp hair follicles from two human donors were pre-treated with ALRN-6924 or vehicle (i.e., placebo), followed by paclitaxel or vehicle, ALRN-6924 significantly increased the number of p21-positive hair matrix keratinocytes and bulge stem cells compared to vehicle or paclitaxel alone, confirming cell cycle arrest ex vivo. Further, pretreatment of paclitaxel-treated human hair follicles with ALRN-6924, led to a reduction in the number of melanin clumps, a marker of hair follicle cytotoxicity and dystrophy, as well as a reduction in apoptosis, pathological mitosis, and DNA damage. Aileron believes that these findings support clinical investigation of ALRN-6924 to prevent both acute and permanent chemotherapy-induced alopecia, in addition to its ongoing evaluation of ALRN-6924 to protect against chemotherapy-induced bone marrow and other toxicities.
About Ailerons Clinical Trials of ALRN-6924
Aileron is on track to initiate a Phase 1b randomized, controlled trial of ALRN-6924 in patients with p53-mutated ER+/HER2- neoadjuvant breast cancer in 2Q 2022. The planned breast cancer trial will evaluate ALRN-6924s protection against chemotherapy-induced bone marrow toxicities, as well as other toxicities, including alopecia, in patients with p53-mutated ER+/HER2- breast cancer treated with a doxorubicin plus cyclophosphamide and docetaxel chemotherapy regimen.
The company is currently enrolling patients in a Phase 1b randomized, double-blind, placebo-controlled trial evaluating ALRN-6924s protection against chemotherapy-induced bone marrow and other toxicities in patients with advanced p53-mutated non-small cell lung cancer undergoing treatment with first-line carboplatin plus pemetrexed with or without immunotherapy. While patients in this trial are monitored for alopecia, historically, only a small percentage of patients treated with carboplatin plus pemetrexed experience acute alopecia. Aileron is on track to report interim results on the first 20 patients enrolled in the NSCLC trial in June 2022 and topline results on 60 patients in 4Q 2022.
About Aileron Therapeutics
Aileron is a clinical stage chemoprotection oncology company that aspires to make chemotherapy safer and thereby more effective to save more patients lives. ALRN-6924, our first-in-class MDM2/MDMX dual inhibitor, is designed to activate p53, which in turn upregulates p21, a known inhibitor of the cell replication cycle. ALRN-6924 is the only reported chemoprotective agent in clinical development to employ a biomarker strategy, in which we exclusively focus on treating patients with p53-mutated cancers. Our targeted strategy is designed to selectively protect multiple healthy cell types throughout the body from chemotherapy without protecting cancer cells. As a result, healthy cells are spared from chemotherapeutic destruction while chemotherapy continues to kill cancer cells. By reducing or eliminating multiple chemotherapy-induced side effects, ALRN-6924 may improve patients quality of life and help them better tolerate chemotherapy. Enhanced tolerability may result in fewer dose reductions or delays of chemotherapy and the potential for improved efficacy.
Our vision is to bring chemoprotection to all patients with p53-mutated cancers, which represent approximately 50% of cancer patients, regardless of type of cancer or chemotherapy. Visit us at aileronrx.com to learn more.
Forward-Looking Statements
Statements in this press release about Ailerons future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements about the potential of ALRN-6924 as a chemoprotective agent, including its ability to prevent both acute and permanent chemotherapy-induced alopecia, and the Companys strategy and clinical development plans. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, would and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether Ailerons cash resources will be sufficient to fund its continuing operations for the periods anticipated or with respect to the matters anticipated; whether initial results of clinical trials will be indicative of final results of those trials or results obtained in future clinical trials, including trials in different indications; whether ALRN-6924 will advance through the clinical trial process on a timely basis, or at all; whether the results of such trials will be accepted by and warrant submission for approval from the United States Food and Drug Administration or equivalent foreign regulatory agencies; whether ALRN-6924 will receive approval from regulatory agencies on a timely basis or at all or in which territories or indications ALRN-6924 may receive approval; whether, if ALRN-6924 obtains approval, it will be successfully distributed and marketed; what impact the coronavirus pandemic may have on the timing of our clinical development, clinical supply and our operations; and other factors discussed in the Risk Factors section of Ailerons annual report on Form 10-K for the year ended December 31, 2021, filed on March 28, 2022, and risks described in other filings that Aileron may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Aileron specifically disclaims any obligation to update any forward-looking statement, whether because of new information, future events or otherwise.
Investor Contact:Stern Investor RelationsAlexander Loboalex.lobo@sternir.com
Media Contact:Liz Melone617-256-6622
Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM and B-NHL and CD19/CD7 Dual-directed Allogeneic…
By daniellenierenberg
SAN DIEGO, Calif., SUZHOU and SHANGHAI, China , May 12, 2022 /PRNewswire/ -- Gracell Biotechnologies Inc. ("Gracell" or the "Company",NASDAQ: GRCL), a global clinical-stage biopharmaceutical company dedicated to developing highly efficacious and affordable cell therapies for the treatment of cancer, today announced the details of three abstracts that it will present at the European Hematology Association 2022 Hybrid Congress (EHA2022 Congress), being held from June 9 June 12 in Vienna, Austria. The abstracts highlight the clinical data from ongoing investigator-initiated trials (IITs) of BCMA/CD19 dual-targeting FasTCAR candidate GC012F in two indications of B-cell non-hodgkin's lymphoma (B-NHL) and relapsed/refractory multiple myeloma (RRMM), and allogeneic TruUCAR candidate GC502 in B-cell acute lymphoblastic leukemia (B-ALL).
"We are very excited to share our data for both our FasTCAR candidate GC012F in two indications of RRMM and B-NHL, and allogeneic TruUCAR candidate GC502 in B-ALL at the EHA2022 Congress," said Dr. Martina Sersch, Chief Medical Officer of Gracell. "The new data, including the expanded indication of GC012F into B-NHL, demonstrates the potential of our platforms and provides further validation. The clinical data of BCMA/CD19 dual-targeting GC012F in the treatment of B-NHL shows promising early results, along with benefits of the next-day manufacturing enabled by the FasTCAR platform. The CD19/CD7 dual-directed CAR-T therapy GC502 is our second allogeneic candidate on our TruUCAR platform, demonstrating the potential wide applicability of the TruUCAR design."
BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of B-NHL
GC012F is an autologous CAR-T therapeutic candidate dual-targeting B cell maturation antigen (BCMA) and CD19. It is developed using Gracell's proprietary FasTCAR platform which enables next-day manufacturing, and is currently being evaluated in IITs in China including in RRMM and B-NHL. GC012F is the first BCMA/CD19 dual-targeting CAR-T in human trials for B-NHL.
Gracell will present the early results of the first-in-human phase 1 IIT in China evaluating the safety and tolerability of GC012F in B-NHL patients. Three patients who had received a median of two prior lines of therapy were enrolled, all of which presented with bulky disease. As of the February 22, 2022 data cutoff date, the enrolled patients had received one single infusion of GC012F at three different doses of 3.7x104 cells/kg and 2-3x105 cells/kg.
All three patients had achieved a complete response (CR) confirmed by PET- CT at day 28 after GC012F infusion. At 3-month follow-up, both of the two assessable patients had ongoing response. No dose-limiting toxicities were observed and no immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. CRS presented as Grade 1 in two patients and Grade 3 in one patient (duration of two days) with no Grade 4 or 5 events.
Details of the presentation are as follows:
BCMA/CD19 Dual-Targeting FasTCAR-T GC012F for the Treatment of RRMM
Gracell will also present as an oral abstract presentation the updated results from the first-in-human IIT evaluating GC012F for the treatment of RRMM patients. This data is currently under embargo and will be published on the EHA2022 Hybrid Congress website on Thursday, May 26 concurrently with ASCO.
Details of the presentation are as follows:
CD19/CD7 Dual-directed Allogeneic TruUCAR-T GC502 for the Treatment of B-ALL
GC502 leverages the novel dual-directed CAR design of Gracell's proprietary TruUCAR platform, designed to generate high-quality allogeneic CAR-T cell therapies that can be administered "off-the-shelf" at lower cost and with faster patient's access. TruUCAR-enabled GC502 utilizes the dual-directed CAR design with one CAR targeting CD19 on malignant cells and a second CAR targeting CD7 to suppress host-versus-graft rejection. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells.
Between September 2021 and January 2022, four r/r B-ALL patients were enrolled and treated in an open-label, non-randomized, prospective IIT in China in two different dose levels and with two different formulations. Patients were heavily pretreated, and all had previously received either autologous or donor derived CD19 or CD19/CD22 targeted CAR-T therapy. As of the January 28, 2022 data cutoff date, all four patients had received a single dose of GC502, including one patient at dose level 1 (DL1) 1.0x107 cells/kg and three patients at dose level 2 (DL2) 1.5x107 cells/kg. Patients received a Flu/Cy based lymphodepletion regimen prior to treatment with GC502.
Three of four patients achieved minimal residual disease negative complete response or complete response with incomplete count recovery (MRD- CR/CRi), and one patient achieved a partial response at month one and subsequently received allogeneic hematopoietic stem-cell transplantation (allo-HSCT) on day 39.
Cytokine release syndrome (CRS) presented as Grade 2 and Grade 3 with no Grade 4 or 5 events. No immune effector cell-associated neurotoxicity syndrome (ICANS) or acute graft-versus-host disease (aGvHD) were observed.
Details of the presentation are as follows:
For more information about the EHA2022 Hybrid Congress, visit http://www.ehaweb.org.
About GC012F
GC012F is a FasTCAR-enabled dual-targeting CAR-T product candidate that is currently being evaluated in IIT studies in China for the treatment of multiple myeloma and B-cell non-Hodgkin's lymphoma. GC012F simultaneously targets CD19 and BCMA to drive fast, deep and durable responses, which can potentially improve efficacy and reduce relapse in multiple myeloma and B-NHL patients.
About B-NHL
Non-Hodgkin's lymphoma (NHL) is a group of blood cancers that developed from lymphocytes, most commonly derived from B cells (B-NHL). Globally, approximately 510,000 patients are diagnosed with NHL every year with about 80,470 patients expected to be diagnosed with NHL in the United States in 2022[1]. B-NHL accounts for approximately 85% of NHL diagnoses.
[1] Data source: American Cancer Society
About GC502
GC502 is a TruUCAR-enabled CD19/CD7 dual-directed, off-the-shelf allogeneic CAR-T product candidate that is being studied in an ongoing Phase 1 IIT in China for the treatment of B-cell malignancies. GC502 is manufactured using T cells from non-human leukocyte antigen (HLA) matched healthy donors. An enhancer molecule is embedded in the basic construct of TruUCAR to enhance proliferation of TruUCAR T cells. Optimized for CD19/CD7 dual-CAR functionality and in vivo durability, GC502 has demonstrated robust anti-tumor effects with potential to suppress host versus graft (HvG) rejection in preclinical models.
About B-ALL
Acute lymphoblastic leukemia (ALL) is a type of blood cancer characterized by proliferation of immature lymphocytes in the bone marrow, which can involve either T lymphocytes (T-ALL), or B lymphocytes (B-ALL). Globally, approximately 64,000 patients are diagnosed with ALL every year with an estimated 6,660 new cases to be diagnosed in the United States in 2022[2]. B-ALL accounts for 75% of ALL diagnoses in adults.
[2] Data source: American Cancer Society
About FasTCAR
CAR-T cells manufactured on Gracell's proprietary FasTCAR platform appear younger, less exhausted and show enhanced proliferation, persistence, bone marrow migration and tumor cell clearance activities as demonstrated in preclinical studies. With next day manufacturing, FasTCAR is able to significantly improve cell production efficiency which may result in meaningful cost savings, and, together with fast turnaround time, enables enhanced accessibility of cell therapies for cancer patients.
About TruUCAR
TruUCAR is Gracell's proprietary technology platform and is designed to generate CAR-T cell therapies from high quality allogeneic T cells that can be administered "off-the-shelf" at lower cost and with improved accessibility of cell therapies for cancer patients. With differentiated design enabled by gene editing, TruUCAR is designed to control HvG as well as GvHD without the need for being co-administered with additional strong immunosuppressant after conventional lymphodepletion. The novel dual-CAR design allows tumor antigen-CAR moiety to target malignant cells, while the CD7 CAR moiety is designed to suppress rejection (HvG response) of allogeneic CAR-T cells by host T and NK cells (HvG).
About Gracell
Gracell Biotechnologies Inc.("Gracell") is a global clinical-stage biopharmaceutical company dedicated to discovering and developing breakthrough cell therapies. Leveraging its pioneering FasTCAR and TruUCAR technology platforms and SMART CARTMtechnology module, Gracell is developing a rich clinical-stage pipeline of multiple autologous and allogeneic product candidates with the potential to overcome major industry challenges that persist with conventional CAR-T therapies, including lengthy manufacturing time, suboptimal cell quality, high therapy cost, and lack of effective CAR-T therapies for solid tumors. For more information on Gracell, please visit http://www.gracellbio.com.Follow @GracellBio on LinkedIn.
Cautionary Noted Regarding Forward-Looking Statements
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the expected trading commencement and closing date of the offering. The words "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "plan," "potential," "predict," "project," "should," "target," "will," "would" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including factors discussed in the section entitled "Risk Factors" in Gracell's most recent annual report on Form 20-F as well as discussions of potential risks, uncertainties, and other important factors in Gracell's subsequent filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Gracell specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. Readers should not rely upon the information on this page as current or accurate after its publication date.
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Gracell Biotechnologies to Present Clinical Data on BCMA/CD19 Dual-targeting CAR-T GC012F in RRMM and B-NHL and CD19/CD7 Dual-directed Allogeneic...
Heart, cancer and diabetes projects among winners of funding boost for stem cell therapies – The Globe and Mail
By daniellenierenberg
Dr. Sara Vasconcelos in the laboratory at Toronto General Hospital on May 11.Christopher Katsarov/The Globe and Mail
When Sara Vasconcelos talks about her work, it sounds as if shes in the restoration business. But instead of repairing damaged buildings, the researcher at Torontos University Health Network wants to fix damaged hearts by using stem cells to rebuild cardiovascular tissue.
Now, Dr. Vasconcelos is one step closer to achieving that goal with a $3-million grant from the Stem Cell Network, a Canadian research funding organization. Her effort is one of 32 projects across the country that rose to the top in a competition for in the largest outlay of federal funding for regenerative medicine in 20 years.
On Thursday, the Ottawa-based network announced a total of $19.5-million in awards, which together with matching funds from various partners, will translate into $42-million for research and clinical trials over the next three years. The funding will enable the work of more than 400 scientists, clinicians and trainees, the organization said.
Its a big step, said Dr. Vasconcelos, who said she will use her award to build on preliminary findings obtained using rats. She will next work with pig hearts, which offer a much closer analogue to the human organ.
While doing so, she also hopes to overcome a barrier that has stood in the path of those who are trying to repair hearts using cardiomyocytes heart tissue cells that are grown from embryonic stem cells. The problem is that the replacement cells wither away if they are not nourished and kept alive by blood vessels.
As part of her project Dr. Vasconcelos aims to use a technique in which small sections of microscopic blood vessels are harvested from human fat and implanted along with the heart cells.
The microvessels that are like Lego pieces, she said. You can put a whole bunch of them in with the stem cell-derived cardiomyocytes and they will connect to each other and connect to the host vessels that carry blood.
With her grant secured, Dr. Vasconcelos said she is assembling the team that will test the method on pig hearts later this year. Ultimately, her goal is to develop the technique into a therapy that can restore cardiac function in human patients following a heart attack, she said.
Among the other projects to win funding are some that are already heading for clinical studies. That includes a large study led by Guy Sauvageau, a hematologist at Maisonneuve-Rosemont Hospital in Montreal, that involves developing engineered blood stem cells to treat leukemia.
Working with a group of clinical sites in the U.S., Dr. Sauvageau and his team have already had success at treating patients with leukemia who relapse. The new project will involve introducing genetical engineered stem cells into people who are better able to withstand cancer treatment and facilitate recovery.
Between 10,000 and 20,000 patients a year would benefit from this kind of therapy, Dr. Sauvageau said.
In the future, he added, the study could open the door to teaching the body to continually produce and replenish its own cancer-killing immune cells rather than having those cells created externally and infused in a form of treatment know as CAR T-cell therapy.
As part of another of the funded projects, David Thompson at the Vancouver Coastal Health Research Institute will conduct clinical trials for one of the worlds first genetically engineered cell replacement therapies for type 1 diabetes.
Dr. Sara Vasconcelos points to an image of vascular tissue in the laboratory at Toronto General Hospital where they engineer cell and tissue regeneration.Christopher Katsarov/The Globe and Mail
The diversity of the projects highlights the increasing prominence of stem cells in multiple domains of health research, an area where Canada has a long track record of success ever since University of Toronto researchers James Till and Ernest McCullough established the existence of stem cells cells which can differentiate into more specialized types in bone marrow in 1961.
Tania Bubela, dean of health sciences at Simon Fraser University in Burnaby, B.C., said the kind of funding the Stem Cell Network provides helps bridge a crucial gap between fundamental laboratory research and proven therapies for patients.
What weve realized over time is that where you get public sector investments to close the funding gap is exactly in that translational space from preclinical into early stage clinical trials, Dr. Bubela said. Once you have that proof that things are going to work and that they can be taken up by the health system, thats when venture capital starts to get interested.
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Heart, cancer and diabetes projects among winners of funding boost for stem cell therapies - The Globe and Mail
Meet the Canadian researcher determined to take the animals out of lab testing – CBC.ca
By daniellenierenberg
Lab animalshave been an essential part of life-altering and lifesaving scientific research and discovery. But a growing number of scientists are calling for an end to their use, and pushing for new methods that can better replicate human biology instead.
Among them is biomedical researcher Dr. Charu Chandrasekera. She'sthe founder and executive director of the Canadian Centre for Alternatives to Animal Methods at the University of Windsor. Here is part of her conversation with Quirks & Quarks host Bob McDonald.
Animal testing historically has been considered a regrettable necessity in the quest to save human lives. Why do you think this is not the case?
Animals have played an integral role in science over the past century or more, to the point where we have made them the gold standard for human biology. And therein lies the problem.
Over 90 per centof drugs tested to be safe and effective in animals, fail in human clinical trials. And even the ones that make it through, they can still be withdrawn or receiveblack box warnings due to unpredicted side effects in humans. And it's not just the drugs that fail, but the drugs that we missed,like the drugs that never made it to human clinical trials because they had some irrelevant side effects in animals. They could very well been safe in humans.So we've likely missed out on many life saving, history altering medications.
Why would a drug work in an animal but not in a human?
Well, there's a very simple answer to that. We humans, we are not 70-kilogram versionsof mice, rats, guinea pigs, rabbits, cats, dogs, sheep or monkeys. We're human. We're separated by hundreds of millions of years of evolution from some of these laboratory animal species.
And it's not only just the species' differences, but there are also so many issues with the way we conduct this research. We have to induce disease by either doing surgical modifications, giving them a high-fat diet. So dietary modifications, genetic modifications, take out a gene, put in a gene, or chemically destroy their pancreas, for example, to create diabetic models. So when you're doing these experimental modifications in these animals, you're really not recreating the human disease. You are creating a version of a human disease.
What motivated you to go from doing animal research in your lab to trying to end the practice altogether?
It was the scientific failures combined with the ethical standards that I was not happy with. So I worked with animal models of heart failure. And while I was doing all these studies, my dad actually had a heart attack and he required quadruple bypass surgery. And while I was with him at the Halifax Heart Centre, I thought to myself, is the research that I'm doing going to truly help humans like my father and everybody else in this ward?
A few weeks later, when I came back to the lab, I ran into this veteran cardiovascular researcher, and he had worked on receptors similar to the ones that I was working on. And I just looked at him and I said, "Do you think these receptors were activated in my dad's heart during his heart attack?" And his response was, "How the hell would I know? We've never looked at this in the human heart."And for me, that day, it was a profound realization. It was almost like an epiphany. What am I doing this for?
Those are the reasons why we should end animal research. Let's explore some of the solutions. What are some of the alternative methods to animals in research that are being developed?
Recreating human biology in a petri dish is no easy feat. There's no single magical method that can replace all animal testing tomorrow morning. It's really all about context of use, fit for purpose. What is the biological question you're trying to answer, and in what context, and how best can we address that?
So we can use human cells and tissues from cadavers and surgical remains. We can take a diseased heart removed during transplant surgery and bring it back to life in the lab, make it beat again, infused with drugs to study cardiac physiology and cardiac toxicity. We can take just a single human cell and obtain hundreds of data points on human DNA and RNA through multiomics studies. We can engineer human tissue, create miniature organ models like organoids to recapitulated complex diseases using stem cell technologies. The field is just exploding.
Can you give me a list of some of the projects that you're working on at your centreright now?
We currently have liver, gut, kidney, lung and blood brain barrier models in development. And we have a number of projects that incorporate these tissues in different configurations to create disease in a dish, and toxicity on a chip. One of the first disease models we're creating is diabetes in a dish, and we're also doing Alzheimer's in a dish. We actually have a project designed specifically to reduce and replace toxicity testing in dogs. And we even have an eco-toxicology project where we're using fish lines to replace toxicity testing on live fish.
This is all based on evidence now. So for some of these methods that we have, we are already seeing that they are able to recapitulate these human responses. We can actually look at the data that we get from using these new technologies and compare them against existing data. But we are also seeing things like new data where we're going back and reevaluating these old drugs that failed in one system and then putting them through a human biology based system. And we're seeing that they are able to predict human biology better.
How hopeful are you that we can make this shift away from using animals in scientific research?
I'm actually very hopeful that we will be able to shift away from this animal-centred paradigm to one where human biology is the gold standard and humans are the quintessential animal model. There are scientific, innovative financial and legislative efforts happening around the world to make this happen.
The goal really is to reduce as much as possible at this point. And even if we needed to use animals, could they become the last resort that you are only using, you know, five rats, for example, for a procedure that required 400 rats before?So because of all of these efforts happening globally, I'm very hopeful.
Produced by Amanda Buckiewicz. This interview has been edited for length and clarity.
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Meet the Canadian researcher determined to take the animals out of lab testing - CBC.ca
Scientists Rejuvenate Skin Cells by 30 Years, with Pioneering Potential – BioSpace
By daniellenierenberg
As previously reported by BioSpace, a group of scientists from The Babraham Institutein the United Kingdom was able to successfully rejuvenate skin cells by a full 30 years.
The research team published a study in eLife Sciences last month describing their process of using induced pluripotent stem cell (iPSC) reprogramming to reverse aging effects at the cellular level.
Study co-author Ins Milagre told BioSpace that the research process was a team effort. In Lead Author Wolf Reiks lab, she was working on cell reprogramming while a colleague focused on the epigenetic clock.
Milagre came into her research career driven by an early interest in biology. I was fascinated by biology all of my life. I had a very good biology teacher when I was in high school, she said.
She explained that she was also a huge fan of the drama series The X-Files, seeing Gillian Anderson's character, Dana Scully, as a role model. I thought that being a scientist must be very cool. This combination made me decide to go into biology.
The research teams original hypothesis came from knowing that we can easily program cells to be zero years of age. No matter what age they are in the beginning, the cells normally reprogram back to embryonic age, or zero years of age.
Though reprogrammed embryonic cells are free of gradual aging decline, they lack identity and thus function. The research team began to consider what would happen if they could get the cells to only partially rejuvenate.
With embryonic cells, downstream applications can be a problem. We thought that maybe we could just rejuvenate the cells and then coax them back into being the cell of origin, Milagre explained. At first, the idea was casually discussed over happy hour, but then the team found that preliminary experiments yielded promising results.
They utilized Yamanaka factors (Oct4, Sox2, Klf4, c-Myc), which are typically used to differentiate cells into the embryonic stem cell stage. Instead of allowing the full time that it takes for cells to get to the embryonic life stage, we decided to stop the reprogramming process halfway through, Milagre said.
By doing this, we were able to get the cells to a younger age. They were easily reverted back to the original cell type, which in our case, were skin cells. Pausing the process in the middle allowed the cells to become a younger version of the same cell type. The researchers named the novel method maturation phase transient reprogramming (MPTR).
What I find very exciting about this study is that we showed that it's possible to rejuvenate cells, she said. Though the Yamanaka factors have been used in other labs, the Babraham Institute team was the first to rejuvenate cells by a full 30 years.
Courtesy of the Babraham Institute
The scientists observed several benefits of the functionally younger cells. The skin cells were better able to produce collagen, and they were responding better to wound healing sites, Milagre said. The above photo depicts the collagen levels of the skin cells before and after rejuvenation. On the left are the original 53-year-old skin cells, and on the right are the reprogrammed cells. The collagen levels are depicted in red.
Milagre noted that the study is very preliminary, with much more research to be completed before the technology is safe and available. We only tested this in skin cells, so we don't know if this is also possible in other cell types, though we believe that it probably is based on similar work from other groups.
Another element that must be studied is how the technology will work without using the same viral vectors. We need to make a safer technology to do this. As a proof of principle, we showed that it's possible to rejuvenate cells by 30 years. Now, we need to do more research to be able to eventually move this technology into a more clinical setting.
Once the technology is safe and ready, Milagre noted that many downstream applications could be possible. We can think about trying to tackle neurodegenerative and degenerative disorders as well as ameliorating some aging effects. If we can get cells to be functionally younger, even if we don't expand peoples lives, we might be able to give people a better quality of life.
Reik explained in an earlier article that the findings could eventually lead to targeting specific genes that would be able to rejuvenate without any reprogramming. Milagre said that Yamanaka factors are working as pioneers that can start new gene expression programs. If we understand which genes are being activated downstream, we can eventually think about modulating these genes. We can try switching on a minimum number of effector genes. This would be a way to overcome using viral vectors.
Though potential future benefits of the findings are a long way off, the team is still considering the people they may help down the line. We hope the technology will help people live better lives without diseases, or without the consequences of a disease even if they still have it, Milagre said.
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Scientists Rejuvenate Skin Cells by 30 Years, with Pioneering Potential - BioSpace
Have you heard of the goodness of Swiss apple stem cells? – Times of India
By daniellenierenberg
We all love trying out new skincare products that give our skin that supple plump and glow. Many of us also use anti-ageing and skin firming products to help reduce those stubborn wrinkles, pigmentation and fine lines. Ever heard the saying, An apple a day, keeps the doctor away? Now, what if we told you that this apple can help your skin without you actually having to eat it? Got you wondering how now, did we?Until several years ago, the tart, unappealing variant of the Swiss-grown Uttwiler Sptlauber apples, wasnt proving to add any value in terms of offering. This was until some scientists discovered the unusual longevity of the stem cells that kept these apples alive months after other apples shriveled and fell off their trees. What are stem cells, you ask? Stem cells are extremely unique in a way that they have the ability to go through numerous cycles and cell divisions while maintaining the undifferentiated state. Essentially, stem cells are capable of self-renewal and can transform themselves into other cell types of the same tissue. One of their primary roles is to replenish dying cells and regenerate damaged tissue. Stem cells provide the ability for species to renew and repair themselves. Plants are rooted in the ground and have to survive extreme weather changes, therefore their stem cells contain much stronger antioxidant contents than those of humans cells.
But how does this help your skin? Heres a list of the goodness that Swiss apple stem cells can have on your skin.
The high antioxidant found in plant stem cells supports the skin in combating free radicals that would otherwise cause skin damage. They give your skin the tools to protect itself, offering immense anti-ageing and anti-inflammatory benefits. The boost of antioxidants and amino acids helps boost collagen production and keeps your skin radiant and youthful.
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Have you heard of the goodness of Swiss apple stem cells? - Times of India
Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest – The New York Times
By daniellenierenberg
Saahil Joshi, age 17, Crystal Springs Uplands School, Hillsborough, Calif.: Too Many Cooks Spoil the Broth: The Science and Future of Drug-Drug Interactions
Micah: Salt: The Sapid and Sophisticated Seasoning
Katherine Kricorian, age 17, Santa Susana High School, Simi Valley, Calif.: From Algae to Energy: A Blooming Solution to Pollution
Chloe Lee, age 14, Korea International School Pangyo Campus, Gyeonggi-do, Korea: Do Plants Have Feelings?
Seungjae (Andy) Lee, age 13, Hong Kong International School, Tai Tam, Hong Kong: Keeping Your Pet Friend Forever: Is Cloning a Soul Possible?
Zhuocheng Li, age 16, Green Hope High School, Cary, N.C.: The Blood That Saved Countless Lives
Andrew C. Lin, age 12, Visions in Education Homeschool Academy, Carmichael, Calif.: Breaking the Speech Barrier
Andy Lu, age 16, Desert Vista High School, Phoenix: Hypersonic Flight: Can We Go Faster?
Camille: Sugar and the Body: A Bittersweet Relationship
Natalia Meza, age 17, American School of Madrid, Madrid: What Happens in Vagus, Stays in Vagus?
Aman Mistry, age 17, Smithtown High School, East Saint James, N.Y.: Helping a Blind Man See: The Miracle of Optogenetics
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Lasers, Fish-Skin Bandages and Pain-Free Vaccines: The Winners of Our 3rd Annual STEM Writing Contest - The New York Times
Why haven’t we cloned a human yet? – Livescience.com
By daniellenierenberg
In 1996, Dolly the sheep made headlines around the world after becoming the first mammal to be successfully cloned from an adult cell. Many commentators thought this would catalyze a golden age of cloning, with numerous voices speculating that the first human clone must surely be just a few years away.
Some people suggested that human clones could play a role in eradicating genetic diseases, while others considered that the cloning process could, eventually, eliminate birth defects (despite research by a group of French scientists in 1999 finding that cloning may actually increase the risk of birth defects).
There have been various claims all unfounded, it is important to add of successful human cloning progams since the success of Dolly. In 2002, Brigitte Boisselier, a French chemist and devout supporter of Ralism a UFO religion based on the idea that aliens created humanity claimed that she and a team of scientists had successfully delivered the first cloned human, whom she named Eve.
However, Boisselier was unwilling or indeed unable to provide any evidence, and so it is widely believed to be a hoax.
So why, almost 30 years on from Dolly, haven't humans been cloned yet? Is it primarily for ethical reasons, are there technological barriers, or is it simply not worth doing?
Related: What are the alternatives to animal testing?
"Cloning" is a broad term, given it can be used to describe a range of processes and approaches, but the aim is always to produce "genetically identical copies of a biological entity," according to the National Human Genome Research Institute (NHGRI).
Any attempted human cloning would most likely utilize "reproductive cloning" techniques an approach in which a "mature somatic cell," most probably a skin cell, would be used, according to NHGRI. The DNA extracted from this cell would be placed into the egg cell of a donor that has "had its own DNA-containing nucleus removed."
The egg would then begin to develop in a test tube before being "implanted into the womb of an adult female," according to NHGRI.
However, while scientists have cloned many mammals, including cattle, goats, rabbits and cats, humans have not made the list.
"I think there is no good reason to make [human] clones," Hank Greely, a professor of law and genetics at Stanford University who specializes in ethical, legal and social issues arising from advances in the biosciences, told Live Science in an email.
"Human cloning is a particularly dramatic action, and was one of the topics that helped launch American bioethics," Greely added.
The ethical concerns around human cloning are many and varied. According to Britannica, the potential issues encompass "psychological, social and physiological risks." These include the idea that cloning could lead to a "very high likelihood" of loss of life, as well as concerns around cloning being used by supporters of eugenics. Furthermore, according to Britannica, cloning could be deemed to violate "principles of human dignity, freedom and equality."
In addition, the cloning of mammals has historically resulted in extremely high rates of death and developmental abnormalities in the clones, Live Science previously reported.
Another core issue with human cloning is that, rather than creating a carbon copy of the original person, it would produce an individual with their own thoughts and opinions.
"We've all known clones identical twins are clones of each other and thus we all know that clones aren't the same person," Greely explained.
A human clone, Greely continued, would only have the same genetic makeup as someone else they would not share other things such as personality, morals or sense of humor: these would be unique to both parties.
People are, as we well know, far more than simply a product of their DNA. While it is possible to reproduce genetic material, it is not possible to exactly replicate living environments, create an identical upbringing, or have two people encounter the same life experiences.
So, if scientists were to clone a human, would there be any benefits, scientific or otherwise?
"There are none that we should be willing to consider," Greely said, emphasizing that the ethical concerns would be impossible to overlook.
However, if moral considerations were removed entirely from the equation, then "one theoretical benefit would be to create genetically identical humans for research purposes," Greely said, though he was keen to reaffirm his view that this should be thought of as "an ethical non-starter."
Greely also stated that, regardless of his own personal opinion, some of the potential benefits associated with cloning humans have, to a certain degree, been made redundant by other scientific developments.
"The idea of using cloned embryos for purposes other than making babies, for example producing human embryonic stem cells identical to a donor's cells, was widely discussed in the early 2000s," he said, but this line of research became irrelevant and has subsequently not been expanded upon post-2006, the year so-called induced pluripotent stem cells (iPSCs) were discovered. These are "adult" cells that have been reprogrammed to resemble cells in early development.
Shinya Yamanaka, a Japanese stem cell researcher and 2012 Nobel Prize winner, made the discovery when he "worked out how to return adult mouse cells to an embryonic-like state using just four genetic factors," according to an article in Nature. The following year, Yamanaka, alongside renowned American biologist James Thompson, managed to do the same with human cells.
When iPSCs are "reprogrammed back into an embryonic-like pluripotent state," they enable the "development of an unlimited source of any type of human cell needed for therapeutic purposes," according to the Center of Regenerative Medicine and Stem Cell Research at the University of California, Los Angeles.
Therefore, instead of using embryos, "we can effectively do the same thing with skin cells," Greely said.
This development in iPSC technology essentially rendered the concept of using cloned embryos both unnecessary and scientifically inferior.
Related: What is the most genetically diverse species?
Nowadays, iPSCs can be used for research in disease modeling, medicinal drug discovery and regenerative medicine, according to a 2015 paper published in the journal Frontiers in Cell and Developmental Biology.
Additionally, Greely also suggested that human cloning may simply no longer be a "sexy" area of scientific study, which could also explain why it has seen very little development in recent years.
He pointed out that human germline genome editing is now a more interesting topic in the public's mind, with many curious about the concept of creating "super babies," for example. Germline editing, or germline engineering, is a process, or series of processes, that create permanent changes to an individuals genome. These alterations, when introduced effectively, become heritable, meaning they will be handed down from parent to child.
Such editing is controversial and yet to be fully understood. In 2018, the Council of Europe Committee on Bioethics, which represents 47 European states, released a statement saying that "ethics and human rights must guide any use of genome editing technologies in human beings," adding that "the application of genome editing technologies to human embryos raises many ethical, social and safety issues, particularly from any modification of the human genome which could be passed on to future generations."
However, the council also noted that there is "strong support" for using such engineering and editing technologies to better understand "the causes of diseases and their future treatment," noting that they offer "considerable potential for research in this field and to improve human health."
George Church, a geneticist and molecular engineer at Harvard University, supports Greely's assertion that germline editing is likely to garner more scientific interest in the future, especially when compared with "conventional" cloning.
"Cloning-based germline editing is typically more precise, can involve more genes, and has more efficient delivery to all cells than somatic genome editing," he told Live Science.
However, Church was keen to urge caution, and admitted that such editing has not yet been mastered.
"Potential drawbacks to address include safety, efficacy and equitable access for all," he concluded.
Originally published on Live Science.
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Why haven't we cloned a human yet? - Livescience.com
Cord Blood Banking: Benefits, Cost, and Process – Healthline
By daniellenierenberg
If you are a new or expectant parent, youve probably heard about the option of banking your babys cord blood at birth. The topic can be confusing, and you may have many unanswered questions.
You may be unsure exactly what cord banking involves, why people choose to bank their infants blood, whether its worth it to do so, and how much it costs to bank cord blood.
Heres a simple breakdown of the potential benefits of cord blood banking and how to decide if its right for your family.
At birth, your newborns placenta and umbilical cord contain blood that is rich with potentially lifesaving stem cells. This blood can be removed, stored, and used down the road to treat various diseases and conditions.
Healthcare professionals do not remove cord blood directly from babies or birthing parents. Rather, it comes from the umbilical cord and placenta themselves, according to the American College of Obstetricians and Gynecologists (ACOG).
The stem cells in umbilical cords and placentas are called hematopoietic stem cells. In people with certain health conditions, they can be used to produce healthy new cells and replace damaged cells.
Stem cells are used to treat over 70 types of diseases, according to ACOG. These include:
You might choose to bank your newborns cord blood for several reasons.
First, you may choose to do so if you have a family member with a medical condition that might benefit from stem cell donation. Alternatively, you might want to donate your babys blood to help another person in need of stem cells.
One myth about cord banking is that you child can use the cord blood down the line, should they develop a serious medical concern. This type of transfer where a persons own cord blood is used to treat their health condition is called an autologous transplant.
ACOG notes that autologous transfers are rare.
If your child has a genetic disease, for example, treating them with their own stem cells wouldnt help because these stem cells contain the same genes as the cells that are involved in the disease. Similarly, your own childs stem cells cant be used to treat cancers such as leukemia.
Instead, most cord blood transplants are allogeneic.
This means that your childs stem cells would be used to treat another child or adult. It would require a strong match between the stem cell recipient (the person using the stem cells) and the stem cell donor (your child).
The benefits of cord blood banking depend on your purpose and where you are storing your childs cord blood.
If you are storing your childs blood at a private institution, you may be able to use the stem cells to directly benefit a family member in need, including a close family member or your childs sibling.
Storing your babys cord blood in a public facility has benefits, too. Stem cells can help treat people with many types of health conditions, including cancers and certain metabolic and immunologic conditions, according to the Health Resources & Services Administration.
There are many advantages to using stem cell transplants for treating medical conditions rather than using bone marrow transplants.
According to ACOG, these benefits include:
If you want to have your newborns cord blood collected, you should inform your OB-GYN or birthing professional, such as a midwife, and the hospital or facility where you will give birth. They may need to order special equipment or a cord collecting kit.
Usually, you will need to inform your healthcare team of your choice to bank your infants blood about 6 weeks in advance of your due date. Youll also need to be sure youve signed all the required consent forms.
Cord blood extraction happens in the hospital after birth and after a healthcare professional has clamped and cut the umbilical cord. They will then use a needle to draw blood out of the cord and store in a designated bag.
The entire process is quick about 10 minutes and does not involve direct contact with your baby.
Sometimes, cord blood extraction isnt possible. Reasons for this may include:
After collection, cord blood must be stored very carefully to ensure that its quality is preserved. Each facility has its own protocols and procedures for how this is done.
The Academy of American Pediatrics (AAP) explains certain accrediting institutions oversee the regulation of cord blood storage and cautions that some private cord blood banks may not meet all these standards.
Before agreeing to have your childs cord blood stored at a private facility, you may want to find out:
Cord blood bank accrediting institutions include:
Before considering cord blood donation, its important for you to understand the difference between private and public banks. Heres what to know:
Private banks are usually used by parents who believe that their childs cord blood may be helpful to a family member who has a medical condition.
They require you to pay on an ongoing basis for your childs cord blood to be stored.
Not all private banks are accredited or regulated in the same way that public banks are.
Public banks are free and supported by government or private funds.
Currently, there is very little evidence that storing your childs blood will help your own child fight a medical condition in the future. In fact, if your child needs stem cells to treat a condition, its more likely that they will receive a donation from a public cord bank.
When you donate to a public cord bank, you do not get to decide who will use your childs blood. You are essentially donating your childs cord blood to help a person in need.
Public cord banks are heavily regulated, and cord blood from these banks is used more frequently than cord blood from private banks. In fact, blood from public banks is used 30 times more frequently than from private banks.
Most major health organizations including the Academy of American Pediatrics and the American College of Obstetricians and Gynecologists recommend public cord blood banking.
Another reason these organizations recommend using public cord blood banks is that they are consistently and well regulated.
Cord blood banking at a public cord bank is free, and you will not have to pay any costs if you donate. These institutions are usually supported by federal funds or receive private funding.
On the other hand, private blood cord banks charge fees, and you must pay these fees for the entire time your childs cord blood is stored in these facilities.
Private cord banks generally charge an initial fee for collecting and processing cord blood. After these initial fees, you will also pay annual fees for ongoing storage. Private cord blood banks vary in their fee amounts, but they average about $2,000 for initial fees and between $100 and $175 each year for annual storage fees, per the AAP.
There are many benefits to banking cord blood. But how you do it depends on several factors, including your familys medical needs and your financial situation.
Almost anyone can choose to donate their infants cord blood to a public bank. Doing so may help many people. While most medical institutions do not recommend private cord banking, this may be the right choice for you if you have a family member who might use the cord blood you bank to treat a health condition.
Either way, its a good idea to speak with your healthcare professional before deciding on whether to bank your babys cord blood. They can also advise you on the best way to do it and which type of blood bank may best meet your needs.
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Cord Blood Banking: Benefits, Cost, and Process - Healthline
Sugared proteins called proteoglycans start to give up their secrets – EurekAlert
By daniellenierenberg
image:A team at Scripps Research demonstrated how protein-sugar clusters called proteoglycans can guide processes like cell maturation and neuronal synapse formation, among other functions. As one example, pictured, semi-synthetic syndecan-1 proteoglycan rescues the maturation of mouse embryonic stem cells into neural precursor cells (red and green). view more
Credit: Meg Critcher, Scripps Research
LA JOLLA, CAScientists at Scripps Research have developed a set of methods for the closer study of one of the least-accessible, least-understood players in biology: protein-sugar conjugates called proteoglycans.
These molecules are often thickly present on the surfaces of cells and are known to have a broad set of functions in the body, though how they work and how their dysfunctions contribute to diseases are largely mysteries.
The scientists, who report their work in Nature Chemical Biology on May 12, 2022, devised synthetic proteoglycans that closely mimic real ones but have convenient chemical handles for modifying them. These and other aspects of their research platform enable the systematic study of how proteoglycans structure affects their functions in health and disease. The scientists demonstrated the effectiveness of their platform by using it to make new discoveries about proteoglycans roles in early cell development and in cancer cell spreading.
Were essentially unpacking the complexity of these molecules by constructing them in a modular way ourselves, and studying them in a tightly controlled environment, says study senior author Mia Huang, PhD, associate professor in the Department of Molecular Medicine at Scripps Research.
A proteoglycan starts as just a proteinthe so-called core proteinbut this protein contains special sites where any of a variety of sugar-related molecular chains called glycosaminoglycans (GAGs) can be linked. Within the cell where the protein originates, enzymes catalyze the attachment of GAGs to it, and this newborn proteoglycan normally is further decorated with clusters of sulfur and oxygen atoms called sulfates. The finished proteoglycan may be anchored into the cell membrane, its GAG chains waving in the extracellular fluid like seagrass, or it may be secreted from the cell to perform other functions.
With such complexity, it is no surprise that proteoglycans have versatile functionsthey are present in virtually all tissues, including cartilage, collagen, bone, skin, blood vessels, brain cells and mucosal surfaces. They help steer processes such as cell maturation, cell adhesion, cell migration, and neuronal synapse formation; serve as receptors for protein signaling partners; and are even used by some viruses and bacteria to latch onto cells. But proteoglycans complexity also means that how they do what they do, and with what partners, remains largely undiscovered. Scientists arent even certain how many proteoglycans there are in human and other mammalian cellsalthough there are at least dozens.
Huang and her team, including first authors Timothy OLeary, PhD and Meg Critcher, respectively a postdoctoral researcher and doctoral candidate in the Huang Lab during the study, constructed proteoglycan core proteins that are almost identical to known core proteins, but contain special molecular handles enabling the researchers to change the numbers and locations and types of GAG chains that bind to them. This allows the researchers to study systematically how the function of a proteoglycan changes as its GAG arrangement changes.
The researchers also developed techniques allowing them to anchor their proteoglycans in cell membranes or to let them float freely, to see how this affects proteoglycans functions in different circumstances.
Using their synthetic versions of common proteoglycans called syndecans, the scientists were able to study the respective contributions of GAG chains and core proteins. Specifically, they looked at two key biological processes mediated by syndecans: the maturing of stem cells, and the spreading of breast cancer cells on an extracellular matrix.
We learned from these experiments that not only the GAG chains but also the core proteins contribute to proteoglycan function, says Critcher. Notably, we also found that proteoglycans role in cancer cell spreading depends heavily on whether they are anchored to the cell membrane or free-floating.
The team also incorporated a method called proximity tagging to help them identify proteoglycans interaction partners. Huang and colleagues are now using this, and their modular construction technique, to study the interactions of syndecans and other proteoglycans in different contextsand with different GAG arrangementsand otherwise to explore their structures and functions.
Chemical editing of proteoglycan architecture was co-authored by Timothy OLeary, Meg Critcher, Tesia Stephenson, Xueyi Yang, Abdullah Hassan, Noah Bartfield, Richard Hawkins, and Mia Huang.
Funding for the research was provided by the National Institutes of Health (R00HD090292, R35GM142462).
About Scripps Research
Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more atwww.scripps.edu.
Nature Chemical Biology
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Sugared proteins called proteoglycans start to give up their secrets - EurekAlert
Supporting the gastrointestinal microenvironment during high-dose chemotherapy and stem cell transplantation by inhibiting IL-1 signaling with…
By daniellenierenberg
Mucosal barrier injury (MBI) in the gastrointestinal tract remains a major clinical obstacle in the effective treatment of hematological malignancies, driving local and systemic complications that negatively impact treatment outcomes. Here, we provide the first evidence of hyper-activation of the IL-1/CXCL1/neutrophil axis as a major driver of MBI (induced by melphalan), which supports evaluating the IL-1RA anakinra, both preclinically and clinically. Our data reinforce that strengthening the mucosal barrier with anakinra is safe and effective in controlling MBI which in turn, stabilises the host microbiota and minimises febrile events. Together, these findings represent a significant advance in prompting new therapeutic initiatives that prioritise maintenance of the gut microenvironment.
The IL-1/CXCL1/neutrophil axis is documented to drive intestinal mucosal inflammation, activated by ligation of intestinal pattern recognition receptors, including toll-like receptors (TLRs)31. In the context of MBI, TLR4 activation is known to drive intestinal toxicity32, 33, however targeting TLR4 directly is challenging due to emerging regulation of tumour response34,35,36,37. As such, we selected anakinra as our intervention to inhibit inflammatory mechanisms downstream of TLR4. While anakinra was able to minimise the intensity and duration of MBI, it did not completely prevent it with comparable citrulline dynamics across animal groups in the first 48h after melphalan treatment. This reflects the core pathobiological understanding of MBI which is initiated by direct cytotoxic events which activate a cascade of inflammatory signalling that serve to exacerbate mucosal injury and the subsequent breakdown of the mucosal barrier33. By preventing this self-perpetuating circle of injury with anakinra, we were able to effectively minimise the duration of MBI and thus have a profound impact on the clinical symptomology associated with MBI including weight loss and anorexia. These findings firstly highlight the cluster of (pre-)clinical symptoms related to MBI (malnutrition, anorexia, diarrhea)38 and suggest that the mucoprotective properties of anakinra will provide broader benefits to the host, mitigating the need for intensive supportive care interventions (e.g. parenteral nutrition).
In line with our hypothesised approach, minimising the duration of MBI reduced secondary events including enteric pathobiont expansion and fever. This again reiterates that changes in the host microbiome and associated complications can be controlled by strengthening the mucosal barrier39. It can be postulated that by minimising the intensity of mucosal injury, the hostility of the microbial environment is reduced ensuring populations of commensal microbes to be maintained. This is supported by our results with the abundance of Faecalibaculum maintained throughout the time course of MBI. Faecalibaculum is a potent butyrate-producing bacterial genus documented to control pathogen expansion by acidification of the luminal environment. Administration of Faecalibacteria prausnitzii has been shown to reduce infection load in a model of antibiotic-induced Clostridioides difficile infection, whilst also showing mucoprotective benefits in models of MBI40, 41. Furthermore, it is documented to cross feed other commensal microbes increasing colonization resistance. Together, these underscore the luminal benefits of strengthening the mucosal barrier and suggest that maintenance of commensal microbes is central to minimizing translocation events and subsequent BSI.
In our clinical Phase IIA study with 3+3 design, we have shown that treatment with anakinra, up until a dose of 300mg, appears to be safe, feasible, and tolerated well. Of course, the sample size of this study was relatively small. However, anakinra was previously evaluated for its efficacy in the treatment of acute and chronic GvHD in patients allogeneic HSCT. In these studies, patients were treated for a similar time period (with higher doses of anakinra). No differences were seen between the anakinra and placebo group regarding (S)AEs, including infections and time to neutrophil recovery. There were no significant changes in our exploratory analyses, however, it was of note to see marked increase in IL-10 in patients that received 300mg anakinra. This may reflect anakinras capacity to promote anti-inflammatory signaling as observed in COVID-19 related respiratory events42. However, with our sample size it is not possible to make any conclusions on this mechanism. Our conclusion is that the recommended dose (RP2D) for anakinra is 300mg QD, which will be investigated in Phase IIB trial (AFFECT-2 study: Anakinra: Efficacy in the Management of Fever During Neutropenia and Mucositis in ASCT; clinicaltrials.gov identifier NCT04099901)43.
While encouraging, our data must be viewed in light of some limitations. Most importantly, our animal model purposely did not include any antimicrobials as we aimed to dissect the true contribution of MBI in pathogen expansion and subsequent febrility. While it is unclear if melphalan has a direct cytotoxic effect on the microbiota, it is likely that MBI drives dysbiosis with antibiotics serving to exacerbate these changes, with previous data demonstrating no direct impact of specific chemotherapeutic agents on microbial viability44. As such, assuming dysbiosis is secondary to mucosal injury as recently demonstrated45, we anticipate that anakinra will still have an appreciable impact on the severity of dysbiosis and may even prompt more protocolised/limited antibiotic use. Similarly, while we used body temperature as an indicator of BSI, we did not culture peripheral blood or mesenteric lymph nodes as was performed in our animal model development. The ability of anakinra to prevent BSI and thus minimise antibiotic use will be best evaluated in AFFECT-2 where routine blood culture is performed. It is also important to consider that we detected episodes of bacteremia in our participants that were likely caused by skin colonizing organisms; a mechanism anakinra will not influence. While these are expected in HSCT recipients, the majority of infectious cases originate from the gut, and we therefore anticipate anakinras capacity to strengthen the mucosal barrier will be clinically impactful in our next study. It must also be acknowledged that limited mechanistic investigations were conducted to identify the way in which anakinra provided mucoprotection. It is well documented that MBI is highly multifactorial, involving mucosal, microbial and metabolic dysfunction33, 46; each of which is mediated through aberrant cytokine production. It is therefore unlikely that anakinra will affect distinct pathways, instead dampening multiple mechanisms. In translating this evidence to the clinic, the impact of anakinra on symptom control is of greater significance than mechanistic insight.
In conclusion, we have demonstrated that not only is anakinra safe in HSCT recipients treated with HDM, but may also be an effective strategy to prevent acute MBI. Our data are critical in supporting new antibiotic stewardship efforts directed at mitigating the emerging consequences of antibiotic use. We suggest that minimizing the severity and duration of MBI is an important aspect of infection control that may optimize the efficacy of anti-cancer treatment, decreasing its impact on antibiotic resistance and the long-term complications associated with microbial disruption.
This study is reported using the ARRIVE guidelines for the accurate and reproducible reporting of animal research.
All animal studies were approved by the Dutch Centrale Commissie Dierproeven (CCD) and the Institutional Animal Care and Use Committee of the University Medical Centre Groningen, University of Groningen (RUG), under the license number 171325-01(-002). The procedures were carried out in accordance with the Dutch Experiments on Animals (Wet op de Dierproeven) and the EU Directive 2010/63/EU. All animals were individually housed in conventional, open cages at the Centrale Dienst Proefdieren (CDP; Central Animal Facility) at the University Medical Centre Groningen. Rats (single housed) were housed under 12h light/dark cycles with ad libitum access to autoclaved AIN93G rodent chow and sterile water. All rats acclimatised for 10days and randomised to their treatment groups via a random number sequence generated in Excel. Small adjustments were made to ensure comparable body weight at the time of treatment and cages were equally distributed across racks to minimise confounding factors. HRW was responsible for animal allocation and assessments while RH/ARDSF performed treatments. Softened chow and subcutaneous saline were provided to rats to reduce suffering/distress and were humanely euthanised if a clinical toxicity score>/=12 was observed. This score was calculated based on weight loss, diarrhea, reluctance to move, coat condition and food intake; each of which were assessed 03. At completion of the study, rats were anaesthetised with 5% isoflurane in an induction chamber, followed by cardiac puncture and cervical dislocation (isoflurane provided by a facemask).
We have previously reported on the development and validation of our HDM model of MBI, which exhibits both clinical and molecular consistency with patients undergoing HDM treatment21. During model development, plasma (isolated from whole blood) was collected and stored for cytokine analysis to inform the selection of our intervention. Repeated whole blood samples (75l) were collected from the tail vein into EDTA-treated haematocrit capillary tubes on day 0, 4, 7 and 10.
Cytokines (IFN-, IL-1, IL-4, IL-5, IL-6, IL-10, IL-13, KC/GRO and TNF-) using the Meso Scale Discovery V-Plex Proinflammatory Panel Rat 2 following manufacturers guidelines. On the day of analysis, all reagents were brought to room temperature, samples were centrifuged to remove any particulate matter and diluted 1:4. Data analysis was performed using the Meso Scale Discovery Workbench.
Male albino Wistar rats (150180g) were randomized (Excel number generator) to one of four experimental groups (N=16/group): (1) controls (phosphate buffered saline (PBS)+0.9% NaCl), (2) anakinra+0.9% NaCl, (3) PBS+melphalan, and (4) anakinra+melphalan. Melphalan was administered as a single, intravenous dose on day 0 (5mg/kg, 10mg/ml) via the penile vein under 3% isoflurane anaesthetic. Anakinra was administered subcutaneously (100mg/kg, 150mg/ml) twice daily from day 1 to+4 (8 am and 5pm). N=4 rats per group were terminated at the exploratory time points (day 4, and 7) and N=8 on day 10 (recovery phase) by isoflurane inhalation (3%) and cervical dislocation. The primary endpoint for the intervention study was plasma citrulline, a validated biomarker of MBI19, 47, which was used for all power calculations (N=8 required, alpha=0.05, beta=0.8).
Clinical manifestations of MBI were assessed using validated parameters of body weight, food intake and water intake, as well as routine welfare indicators (movement, posture, coat condition). Rats were weighed daily, and water/food intake monitored by manual weighing of chow and water bottles.
Plasma citrulline is an indicator of intestinal enterocyte mass48, and a validated biomarker of intestinal MBI. Repeated blood samples (75l) were collected from the tail vein into EDTA-treated haematocrit capillary tubes on day 0, 2, 4, 6, 7, 8 and 10. Citrulline was determined in 30l of plasma (isolated from whole blood via centrifugation at 4000g for 10min) using automated ion exchange column chromatography as previously described49.
Whole blood samples (200l) were collected from the tail vein into MiniCollect EDTA tubes on day 0, 4, 7 and 10 for differential morphological analysis which included: white blood cell count (WBC, 109/L), red blood cell count (RBC, 109/L), haemoglobin (HGB, mmol/L), haematocrit (HCT, L/L), mean corpuscular volume (MCV, fL), mean corpuscular haemoglobin (MCH, amol), mean corpuscular hemoglobin concentration (MCHC, mmol/L), platelet count (PLT, 109/L), red blood cell distribution width (RDW-SD/-CV, fL/%), mean platelet volume (fL), mean platelet volume (MPV, fL), platelet large cell ratio (P-LCR, %), procalcitonin (PCT, %), nucleated red blood cell (NRBC, 109/L and %), neutrophils (109/L and %), lymphocytes (109/L and %), monocytes (109/L and %), eosinophils (109/L and %), basophils (109/L and %) and immunoglobulins (IG, 109/L and %). For the purpose of the current study only neutrophils, lymphocytes and monocytes were evaluated.
Core body temperature was used as an indicator of fever. Body temperature was assessed daily using the Plexx B.V. DAS-7007R handheld reader and IPT programmable transponders. Transponders were inserted subcutaneously under mild 2% isoflurane anaesthesia on day 4. Average values from day 4 to 1 were considered as baseline body temperature.
The microbiota composition was assessed using 16S rRNA sequencing in N=8 rats/group. Repeated faecal samples were collected on day 0, 4, 7 and 10 and stored at 80C until analysis. Sample preparation (including DNA extraction, PCR amplification, library preparation), quality control, sequencing and analyses were all performed by Novogene (please see supplementary methods for full description).
All data (excluding 16S data) were analysed in GraphPad Prism (v8.0. Repeated measures across multiple groups were assessed by mixed-effect models with appropriate post-hoc analyses. Terminal data analyses were assessed by one-way ANOVA. Statistical analyses are outlined in figure legends and P<0.05 was considered significant.
This Phase IIA trial (AFFECT-1: NCT03233776, 17/6/2017) aimed to i) assess the safety of anakinra in autologous HSCT recipients undergoing conditioning with HDM, and ii) determine the maximum tolerated dose of anakina (100, 200 or 300mg).
This study was approved by the ethical committee Nijmegen-Arnhem (NL59679.091.16; EudraCT 2016-004,419-11) and performed in accordance with (a) theDeclaration of Helsinki (1964, amended October 2013), (b) Medical Research Involving Human Subjects Act and c) Good Clinical Practice guidelines.We enrolled patients from Radboud University Medical Centre who were at least 18years of age and were scheduled to undergo an autologous HSCT after receiving conditioning with HDM (200mg/m2) for multiple myeloma. All participants provided informed consent. Important exclusion criteria were active infections, a history of tuberculosis or positive Quantiferon, glomular filtration rate<40ml/min, and colonization with highly resistant micro-organisms or with gram-negative bacteria resistant to ciprofloxacin.
Patients were involved in the design of the AFFECT trials, through involvement of Hematon, a patient organization for patients with hemato-oncological diseases in the Netherlands. The project plan, including trial materials, have been presented to patient experts from Hematon. They have given their advice on the project, and provided input on the design of the study as well as on patient information. Patients will also be involved in the dissemination of the results of the AFFECT trials. Information on both the design as well as the outcome of the AFFECT trials is and/or will be available on websites specifically aimed at patients, such as the Dutch website kanker.nl.
Conforming with routine clinical practice and care, study participants were admitted at day 3, treated with melphalan 200mg/m2 at day 2, and received their autologous HSCT at day 0. They were treated with IL-1RA anakinra (Kineret, SOBI) intravenously once daily from day 2 up until day+12.
A traditional 3+3 design was used (Fig. S1), in which the first cohort of patients was treated with 100mg, the next cohort with 200mg and the third cohort with 300mg of anakinra. In this study design, the cohort is expanded when dose limiting toxicities (DLTs) occur. The primary study endpoint was safety, using the common toxicity criteria (CTCAE) version 4.050, as well as the maximum tolerated dose of anakinra (MTD; 100, 200 or 300mg). DLTs were defined as the occurrence of (1) an infection due to an opportunistic pathogen (including Pneumocystis jirovecii pneumonia, mycobacterial infections and invasive mould disease), (2) a suspected unexpected serious adverse reaction (SUSAR), (3) severe non-hematological toxicity grade 34 (meaning toxicity that does not commonly occur in the treatment with HDM and HSCT, or that is more severe than is to be expected with standard treatment) and (4) primary graft failure or prolonged neutropenia (neutrophils have not been>0.5109/l on one single day, assessed on day+21, and counting from day 0).
Secondary endpoints included: incidence of fever during neutropenia (defined as a tympanic temperature38.5C and an absolute neutrophil count (ANC)<0.5109/l, or expected to fall below 0.5109/l in the next 48h), CRP levels, intestinal mucositis as measured by (the AUC of) citrulline, clinical mucositis as determined by daily mouth and gut scores, incidence and type of BSI, short term overall survival (100days and 1year after HSCT), length of hospital stay in days and use of systemic antimicrobial agents, analgesic drugs and total parenteral nutrition (incidence and duration).
Patients received standard antimicrobial prophylaxis including ciprofloxacin and valacyclovir, as well as antifungal prophylaxis (fluconazole) on indication; i.e. established mucosal colonization. Upon occurrence of fever during neutropenia, empirical treatment with ceftazidime was started. The use of therapies to prevent or treat mucositis (i.e. oral cryotherapy) was prohibited. Also, treatment with acetaminophen or non-steroidal anti-inflammatory drugs was not allowed during hospital admission. All other supportive care treatments (i.e. morphine, antiemetics, transfusions, TPN) were allowed.
Laboratory analysis was performed three times a week, which included hematological and chemistry panels and plasma collection for citrulline analysis. Blood cultures were drawn daily from day+4 up until day+12, which was halted upon occurrence of fever. Outside this period, conforming to standard of care, blood cultures were drawn twice weekly and in occurrence of fever. Conforming standard of care, surveillance cultures of mucosal barriers were obtained twice weekly.
Plasma was longitudinally collected from participants throughout the study period for the evaluation of cytokines using the Meso Scale Discovery Customised U-Plex 9-analyte panel following manufacturers guidelines (IL-1/, IL-1RA, CXCL1, TNF, IL-10, IL-17, IL-6, GM-CSF). 16S sequencing was performed by Novogene (as per preclinical analysis methodology).
Other Notable Health Studies & Research From May 11, 2022 – Study Finds
By daniellenierenberg
Worlds 1st Focused Ultrasound Cancer Immunotherapy Center LaunchedUVA Health and the Charlottesville-based Focused Ultrasound Center today announced the launch of theFocused Ultrasound Cancer Immunotherapy Center, the worlds first center dedicated specifically to advancing a focused ultrasound and cancer immunotherapy treatment approach that could revolutionize 21st-century cancer care.
A Study by the Gwangju Institute of Science and Technology Investigates Mercury Contamination in Freshwater Lakes in KoreaDuring the 1950s and 1960s, Minamata Bay in Japan was the site of widespread mercury poisoning caused by the consumption of fish containing methylmercurya toxic form of mercury that is synthesized when bacteria react with mercury released in water.
Researchers identify possible new target to treat newborns suffering from lack of oxygen or blood flow in the brainThe condition, known as hypoxic-ischemic encephalopathy (HIE), can result in severe brain damage, which is why researchers at theCase Western Reserve University School of Medicineand UH Rainbow Babies & Childrens Hospital (UH Rainbow) are studying the condition to evaluate how HIE is treated and develop new, more effective options.
Should You Give Your Child Opioids for Post-Operative Pain Management?Routine head and neck procedures, such as removal of tonsils and adenoids and the placement of ear tubes, may cause moderate to severe pain in pediatric patients.
Two birds with one stone: a refined bioinformatic analysis can estimate gene copy-number variations from epigenetic dataA team led by Dr. Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute, has improved the computational identification of potentially druggable gene amplifications in tumors, from epigenetic data.
Some Shunts Used After Epilepsy Surgery May Risk Chronic HeadachesSurgeons who observe persistent fluid buildup after disconnecting epileptic and healthy brain areas should think twice before installing low-pressure nonprogrammable drainage shunts, according to a study coauthored by Rutgers pediatric and epilepsy neurosurgeonYasunori Nagahamathat found chronic headaches could result from these procedures.
Re-defining the selection of surgical procedure in sufferers with tuberous sclerosis complicatedBy illustrating a number of instances of tuberous sclerosis in sufferers whove undergone surgical resection with seizure-free outcomes, researchers have recognized components that decide choice of sufferers for profitable surgical procedure.
Scientists study links between obesity, age and body chemistryA team of Clemson University scientists is making inroads in understanding the relationship between certain enzymes that are normally produced in the body and their role in regulating obesity and controlling liver diseases.
Clemson scientists discover new tools to fight potentially deadly protozoa that has pregnant women avoiding cat litter boxesNow, a group of researchers from Clemson University have discovered a promising therapy for those who suffer from toxoplasmosis, a disease caused by the microscopic protozoa Toxoplasma gondii.
Rising income inequality linked to Americans declining healthRising levels of income inequality in the United States may be one reason that the health of Americans has been declining in recent decades, new research suggests.
New research to understand how the brain handles optical illusions and makes predictionsNew research projects are underway at the Allen Institute to address these questions through OpenScope, the shared neuroscience observatory that allows scientists around the world to propose and direct experiments conducted on one of the Institutes high-throughput experimental platforms.
Robotic therapy: A new effective treatment for chronic stroke rehabilitationA study led by Dr. Takashi Takebayashi and published in the journal Stroke suggests continuing therapy for chronic stroke patients is still beneficial while suggesting a radical alternative.
Children with history of maltreatment could undergo an early maturation of the immune systemThe acute psychosocial stress states stimulate the secretion of an antibody type protein which is decisive in the first immune defence against infection, but only after puberty.
Toxoplasmosis: propagation of parasite in host cell stoppedA new method blocks the protein regulation of the parasite Toxoplasma gondii and causes it to die off inside the host cell.
Research shows the role empathy may play in musicCan people who understand the emotions of others better interpret emotions conveyed through music? A new study by an international team of researchers suggests the abilities are linked.
Effects of stress on adolescent brains triple networkA new studyinBiological Psychiatry: Cognitive Neuroscience and Neuroimaging, published by Elsevier, has used functional magnetic resonance imaging (fMRI) to examine the effects of acute stress and polyvicitimization, or repeated traumas, on three brain networks in adolescents.
Reform to Mental Health Act must prompt change in support for familiesFamily members of people with severe mental health challenges need greater support to navigate the UKs care system following changes announced in yesterdays Queens Speech, say the authors of a new study published in theBritish Journal of Social Work.
New knowledge about airborne virus particles could help hospitalsMeasurements taken by researchers at Lund University in Sweden of airborne virus in hospitals provide new knowledge about how best to adapt healthcare to reduce the risk of spread of infection.
Guidance developed for rare dancing eyes syndromeExperts from Evelina London Childrens Hospital developed the guidance in collaboration with a worldwide panel of experts and families of children with the condition.
Genetic study identifies migraine causes and promising therapeutic targetsQUT genetic researchers have found blood proteins that cause migraine and have a shared link with Alzheimers disease that could potentially be prevented by repurposing existing therapeutics.
How do genomes evolve between species? The key role of 3D structure in male germ cellsA study led by scientists at the UAB and University of Kent uncovers how the genome three-dimensional structure of male germ cells determines how genomes evolve over time.
Novel Supramolecular CRISPRCas9 Carrier Enables More Efficient Genome EditingRecently, a research team from Kumamoto University, Japan, have constructed a highly flexible CRISPR-Cas9 carrier using aminated polyrotaxane (PRX) that can not only bind with the unusual structure of Cas9 and carry it into cells, but can also protect it from intracellular degradation by endosomes.
Obesity, diabetes and high blood pressure increase mortality from COVID-19 especially among young and middle-aged peopleObesity, impaired blood glucose metabolism, and high blood pressure increase the risk of dying from COVID-19 in young and middle-aged people to a level mostly observed in people of advanced age.
Are most ORR electrocatalysts promising nanocatalytic medicines for tumor therapy?The current searches for medical catalysts mainly rely on trial-and-error protocols, due to the lack of theoretical guidance.
The combination makes the difference: New therapeutic approach against breast cancerResearchers at the University of Basel have now discovered an approach that involves a toxic combination with a second target gene in order to kill the abnormal cells.
Glatiramer acetate compatible with breastfeedingA study conducted by the neurology department of Ruhr-Universitt Bochum (RUB) at St. Josef Hospital on the drug glatiramer acetate can relieve mothers of this concern during the breastfeeding period.
A*STAR, NHCS, NUS And Novo Nordisk To Collaborate On Cardiovascular Disease ResearchThe Agency for Science, Technology and Researchs (A*STAR) Genome Institute of Singapore (GIS) and Bioinformatics Institute (BII), as well as the National Heart Centre Singapore (NHCS), National University of Singapore (NUS), and pharmaceutical company Novo Nordisk have signed an agreement to study the mechanisms underlying cardiovascular disease progressionespecially the condition called heart failure with preserved ejection fraction (HFpEF).
Taking ownership of your healthA study published this month inAge and Ageing by The Japan Collaborate Cohort (JACC) Study group at Osaka University assessed the impact of modifying lifestyle behaviors on life expectancy from middle age onwards.
Experimental evolution illustrates gene bypass process for mitosisResearchers from Nagoya University demonstrated gene bypass events for mitosis using evolutionary repair experiments.
Temporomandibular Disorder-Induced Pain Likely to Worsen in Late Menopause TransitionNew study evaluates the influence of menopause symptoms on the intensity of temporomandibular disorder-induced pain throughout the full menopause transition.
Breathtaking solution for a breathless problemA drop in oxygen levels, even when temporary, can be critical to brain cells. This explains why the brain is equipped with oxygen sensors. Researchers from Japan and the United States report finding a new oxygen sensor in the mouse brain.
How calming our spinal cords could provide relief from muscle spasmsAn Edith Cowan University (ECU) studyinvestigating motoneurons in the spine has revealed two methods can make our spinal cords less excitable and could potentially be usedto treat muscle spasms.
Analysis Finds Government Websites Downplay PFAS Health RisksState and federal public health agencies often understate the scientific evidence surrounding the toxicity of per- and polyfluoroalkyl substances (PFAS) in their public communications, according toan analysispublished today in the journalEnvironmental Health.
Multiple diagnoses are the norm with mental illness; new genetic study explains whyThe study, published this weekin the journalNature Genetics, found that while there is no gene or set of genes underlying risk for all of them, subsets of disordersincluding bipolar disorder and schizophrenia; anorexia nervosa and obsessive-compulsive disorder; and major depression and anxietydo share a common genetic architecture.
Drinkers sex plus brewing method may be key to coffees link to raised cholesterolThe sex of the drinker as well as the brewing method may be key to coffees link with raised cholesterol, a known risk factor for heart disease, suggests research published in the open access journalOpen Heart.
Artificial cell membrane channels composed of DNA can be opened and locked with a keyIn new research, Arizona State University professorHao Yan, along with ASU colleagues and international collaborators from University College London describe the design and construction of artificial membrane channels, engineered using short segments of DNA.
Single cell RNA sequencing uncovers new mechanisms of heart diseaseResearchers at the Hubrecht Institute have now successfully applied a new revolutionary technology (scRNA-seq) to uncover underlying disease mechanisms, including specifically those causing the swelling.
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Other Notable Health Studies & Research From May 11, 2022 - Study Finds
WIN: A beauty box of dreams valued at R3000 – CapeTown ETC
By daniellenierenberg
WIN: A beauty box of dreams valued at R3000
Winters whispers are quickly reaching a crescendo, and that means giving your skin and glam routine a big, warm hug. Finding what products work for you can be a painstaking and expensive task. So, weve put together a fabulous Beauty Box full of goodies just for you.
With the help of expert local beauty Editor, Jade Smith, the Beauty Box has been curated with nothing short of the best products. It contains nine items that, together, are valued at R3 000.
Jade Smith is the beauty brain behind some of South Africas most adored magazines, including Woman&Home, and has over 20 years of experience in the industry. She started her career as a make-up artist and has worked on many international campaigns in London and Europe, including work for iconic brands like Tom Ford and Dove. Every product is personally tried and tested and selected by Jade and only the best makes it into the box.
In sharing a little warmth this winter, Cape {town} Etc is giving away three Beauty Boxes to three lucky winners. Get ready to glow all season long.
1. Afari Overnight Regenerating Cream 50ml
A luxurious overnight skin-repairing cream loaded with potent ingredients to help skin look renewed by morning. It helps to boost natural collagen production and speed up cell turnover for bouncier, smoother skin.
This brand is proudly South African, free from nasties, and cruelty-free.
Explore more onwww.afari.co.zaor@afariskincare
2. SKOON Happy Flora Face Moisturiser 15ml
Join the good bacteria movement and re-balance your skins microbiome. Made with Swiss yoghurt and Quora Noni an active ingredient derived from plant stem cells that help to control bacteria.
This brand is proudly South African, free from nasties, and cruelty-free.
Explore more onwww.skoonskin.comor@skoonskin
3. Gatineau Defi Lift 3D Firming Neck & Dcollet Gel 15ml
A gel formula formulated to help tighten skin and visibly firm the delicate neck and dcollet area thanks to Plant Proteins, encapsulated Hyaluronic Acid and Fixlift technology.
Tip: Use gentle, upward strokes all the way up to the jawline using your hands or your favourite stone roller.
Explore more onwww.gatineau.comor@gatineau_sa
4. Rimmel WonderLuxe Volume Mascara in Black
This mascara promises to give lashes full-bodied volume without looking clumpy or weighing lashes down. It also includes Argan, Maracuja, Marula and Calmellia oils to nourish and protect lashes.
Ophthalmologist tested it, which means its safe for contact lens wearers too.
Explore more onwww.rimmellondon.com/en-zaor@rimmellondonsa
5. Berdoues Azur Riviera 10ml
It can be tricky to find your signature scent, which is why its best to test it first. This one is fresh and clean, perfect for both you and your partner, with marine and aquatic notes softened with Orange Blossom and Jasmine at the heart.
Explore more onwww.berdoues.comor@berdouesgrandscrussa
6. BIODERMA Photoderm AKN Mat Sunscreen Cream SPF 30
A mattifying sun protection fluid thats lighter than air and ideal for all skin types. Furthermore, it helps to prevent the appearance of blemishes while protecting against cellular damage, shielding against UVA and UVB, and free radicals.
Explore more onwww.bioderma.co.zaor@biodermasouthafrica
7. Litchi & Titch Mini Aromatherapy Serum
Made with essential oils and botanical extracts of the highest quality, this blend is made with calmness and serenity in mind. Neroli, Grapefruit and Chamomile are heroed, and the formula is suitable for all skin types.
Tip: Apply 5 to 7 drops of the serum and press onto the skin after misting or dampening skin slightly, then cup your hands over your nose and breathe in to set a calming mood.
This brand is proudly South African, free from nasties, and cruelty-free.
Explore more onwww.litchiandtitchnaturals.comor@litchiandtitchnaturals
8. NUXE rve de miel Face & Body Gel 100ml
An ultra-rich cleansing gel using natural active ingredients such as honey, coconut and sunflower. The formula is gentle, yet effective enough to be used on your face and body, and is especially suitable for dry and sensitive skin.
Tip: Thanks to the deliciously rich and creamy texture, it works wonderfully for shaving.
Explore more onwww.nuxe.comor@nuxe_sa
9. Skin Republic Wrinkle Smooth Complex Sheet Mask
A biodegradable sheet mask packed with Adenosine, Green Tea and Plant Stem Cells was chosen for their skin-firming and texture-smoothing powers.
Explore more onwww.theskinrepublic.co.zaor@skinrepublic
To enter, fill in your details and answer the question below:
*Winners will be announced Monday 15 May 2022.
*Hint: All entrants can expect some exciting news on Monday 15 May 2022.
Question: Which item in the Beauty Box are you most excited to try?
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WIN: A beauty box of dreams valued at R3000 - CapeTown ETC
Plug-and-Play Human Organ-on-a-Chip Can Be Customized to the Patient – SciTechDaily
By daniellenierenberg
The new multi-organ chip has the size of a glass microscope slide and allows the culture of up to four human engineered tissues, whose location and number can be tailored to the question being asked. These tissues are connected by vascular flow, but the presence of a selectively permeable endothelial barrier maintains their tissue-specific niche. Credit: Kacey Ronaldson-Bouchard/Columbia Engineering
Major advance from Columbia Engineering team demonstrates the first multi-organ chip made of engineered human tissues linked by vascular flow for improved modeling of systemic diseases like cancer.
Engineered tissues have become an essential component for modeling diseases and testing the efficacy and safety of drugs in a human context. A key hurdle for researchers has been figuring how to model body functions and systemic diseases with multiple engineered tissues that can physiologically communicate just like they do in the body. However, it is essential to provide each engineered tissue with its own environment so that the specific tissue phenotypes can be maintained for weeks to months, as required for biological and biomedical studies. Making the challenge even more complex is the necessity of linking the tissue modules together to facilitate their physiological communication, which is required for modeling conditions that involve more than one organ system, without sacrificing the individual engineered tissue environments.
Up to now, no one has been able to meet both conditions. Today, a team of researchers from Columbia Engineering and Columbia University Irving Medical Center reports that they have developed a model of human physiology in the form of a multi-organ chip consisting of engineered human heart, bone, liver, and skin that are linked by vascular flow with circulating immune cells, to allow recapitulation of interdependent organ functions. The researchers have essentially created a plug-and-play multi-organ chip, which is the size of a microscope slide, that can be customized to the patient. Because disease progression and responses to treatment vary greatly from one person to another, such a chip will eventually enable personalized optimization of therapy for each patient. The study is the cover story of the April 2022 issue of the journal Nature Biomedical Engineering.
In our study, we cultured liver, heart, bone, and skin, connected by vascular flow for four weeks. These tissues can be generated from a single human induced pluripotent stem cell, generating a patient-specific chip, a great model for individualized studies of human disease and drug testing. Credit: Keith Yeager/Columbia Engineering
This is a huge achievement for usweve spent ten years running hundreds of experiments, exploring innumerable great ideas, and building many prototypes, and now at last weve developed this platform that successfully captures the biology of organ interactions in the body, said the project leader Gordana Vunjak-Novakovic, University Professor and the Mikati Foundation Professor of Biomedical Engineering, Medical Sciences, and Dental Medicine.
Taking inspiration from how the human body works, the team has built a human tissue-chip system in which they linked matured heart, liver, bone, and skin tissue modules by recirculating vascular flow, allowing for interdependent organs to communicate just as they do in the human body. The researchers chose these tissues because they have distinctly different embryonic origins, structural and functional properties, and are adversely affected by cancer treatment drugs, presenting a rigorous test of the proposed approach.
The tissues cultured in the multi-organ chip (skin, heart, bone, liver, and endothelial barrier from left to right) maintained their tissue-specific structure and function after being linked by vascular flow. Credit: Kacey Ronaldson-Bouchard/Columbia Engineering
Providing communication between tissues while preserving their individual phenotypes has been a major challenge, said Kacey Ronaldson-Bouchard, the studys lead author and an associate research scientist in Vunjak-Novakovics Laboratory for Stem Cells and Tissue Engineering. Because we focus on using patient-derived tissue models we must individually mature each tissue so that it functions in a way that mimics responses you would see in the patient, and we dont want to sacrifice this advanced functionality when connecting multiple tissues. In the body, each organ maintains its own environment, while interacting with other organs by vascular flow carrying circulating cells and bioactive factors. So we chose to connect the tissues by vascular circulation, while preserving each individual tissue niche that is necessary to maintain its biological fidelity, mimicking the way that our organs are connected within the body.
The group created tissue modules, each within its optimized environment and separated them from the common vascular flow by a selectively permeable endothelial barrier. The individual tissue environments were able to communicate across the endothelial barriers and via vascular circulation. The researchers also introduced into the vascular circulation the monocytes giving rise to macrophages, because of their important roles in directing tissue responses to injury, disease, and therapeutic outcomes.
All tissues were derived from the same line of human induced pluripotent stem cells (iPSC), obtained from a small sample of blood, in order to demonstrate the ability for individualized, patient-specific studies. And, to prove the model can be used for long-term studies, the team maintained the tissues, which had already been grown and matured for four to six weeks, for an additional four weeks, after they were linked by vascular perfusion.
The researchers also wanted to demonstrate how the model could be used for studies of an important systemic condition in a human context and chose to examine the adverse effects of anticancer drugs. They investigated the effects of doxorubicin a broadly used anticancer drug on heart, liver, bone, skin, and vasculature. They showed that the measured effects recapitulated those reported from clinical studies of cancer therapy using the same drug.
The team developed in parallel a novel computational model of the multi-organ chip for mathematical simulations of drugs absorption, distribution, metabolism, and secretion. This model correctly predicted doxorubicins metabolism into doxorubicinol and its diffusion into the chip. The combination of the multi-organ chip with computational methodology in future studies of pharmacokinetics and pharmacodynamics of other drugs provides an improved basis for preclinical to clinical extrapolation, with improvements in the drug development pipeline.
While doing that, we were also able to identify some early molecular markers of cardiotoxicity, the main side-effect that limits the broad use of the drug. Most notably, the multi-organ chip predicted precisely the cardiotoxicity and cardiomyopathy that often require clinicians to decrease therapeutic dosages of doxorubicin or even to stop the therapy, said Vunjak-Novakovic.
The development of the multi-organ chip began from a platform with the heart, liver, and vasculature, nicknamed the HeLiVa platform. As is always the case with Vunjak-Novakovics biomedical research, collaborations were critical for completing the work. These include the collective talent of her laboratory, Andrea Califano and his systems biology team (Columbia University), Christopher S. Chen (Boston University) and Karen K. Hirschi (University of Virginia) with their expertise in vascular biology and engineering, Angela M. Christiano and her skin research team (Columbia University), Rajesh K. Soni of the Proteomics Core at Columbia University, and the computational modeling support of the team at CFD Research Corporation.
The research team is currently using variations of this chip to study, all in individualized patient-specific contexts: breast cancer metastasis; prostate cancer metastasis; leukemia; effects of radiation on human tissues; the effects of SARS-CoV-2 on heart, lung, and vasculature; the effects of ischemia on the heart and brain; and the safety and effectiveness of drugs. The group is also developing a user-friendly standardized chip for both academic and clinical laboratories, to help utilize its full potential for advancing biological and medical studies.
Vunjak-Novakovic added, After ten years of research on organs-on-chips, we still find it amazing that we can model a patients physiology by connecting millimeter sized tissues the beating heart muscle, the metabolizing liver, and the functioning skin and bone that are grown from the patients cells. We are excited about the potential of this approach. Its uniquely designed for studies of systemic conditions associated with injury or disease, and will enable us to maintain the biological properties of engineered human tissues along with their communication. One patient at a time, from inflammation to cancer!
Reference: A multi-organ chip with matured tissue niches linked by vascular flow by Kacey Ronaldson-Bouchard, Diogo Teles, Keith Yeager, Daniel Naveed Tavakol, Yimu Zhao, Alan Chramiec, Somnath Tagore, Max Summers, Sophia Stylianos, Manuel Tamargo, Busub Marcus Lee, Susan P. Halligan, Erbil Hasan Abaci, Zongyou Guo, Joanna Jackw, Alberto Pappalardo, Jerry Shih, Rajesh K. Soni, Shivam Sonar, Carrie German, Angela M. Christiano, Andrea Califano, Karen K. Hirschi, Christopher S. Chen, Andrzej Przekwas and Gordana Vunjak-Novakovic, 27 April 2022, Nature Biomedical Engineering.DOI: 10.1038/s41551-022-00882-6
Originally posted here:
Plug-and-Play Human Organ-on-a-Chip Can Be Customized to the Patient - SciTechDaily
Barbie unveils first doll with hearing aid as part of inclusivity push – The Guardian US
By daniellenierenberg
In a new set of firsts for Barbie, the latest in its most diverse and inclusive doll line yet will include a Barbie with hearing aids and a Ken doll with vitiligo, a condition where skin loses its pigment cells.
Mattels global head of Barbie Dolls, Lisa McKnight, said in a statement: Its important for kids to see themselves reflected in product and to encourage play with dolls that dont resemble them, to help them understand and celebrate the importance of inclusion.
Mattel said it worked alongside Dr Jen Richardson, a practitioner in educational audiology, to accurately model behind-the-ear devices for the doll.
Im honored to have worked with Barbie to create an accurate reflection of a doll with behind-the-ear hearing aids, Richardson said. As an educational audiologist with over 18 years of experience working in hearing loss advocacy, its inspiring to see those who experience hearing loss reflected in a doll.
Im beyond thrilled for my young patients to see and play with a doll who looks like them.
The 2022 Fashionistas line, out next month, will also feature a Barbie with a prosthetic leg, a Barbie who uses a wheelchair, and male dolls that are thinner and less muscular.
Barbie has described its upcoming 175-look collection as its most diverse and inclusive doll line, offering a variety of skin tones, eye colors, hair colors and textures, body types, disabilities, and fashions, to inspire even more stories.
In recent years, Barbie has launched more inclusive doll lines including one inspired by real-life women who have upended societal norms. In 2017, Barbie released a doll wearing a hijab, modelled after Ibtihaj Muhammad, a fencer who became the first American to compete and win an Olympic medal wearing the garment.
Last year, Barbie launched a set of dolls that honoured Covid workers including vaccinologists, nurses and paramedics.
One of the dolls is modelled after Dame Sarah Gilbert, the co-creator of the Oxford/AstraZeneca vaccine.
I am passionate about inspiring the next generation of girls into Stem careers and hope that children who see my Barbie will realise how vital careers in science are to help the world around us, Gilbert told the Guardian.
My wish is that my doll will show children careers they may not be aware of, like a vaccinologist.
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Barbie unveils first doll with hearing aid as part of inclusivity push - The Guardian US
World Thalassemia Day 2022: Why India Is The Thalassemia Capital Of The World – NDTV Doctor
By daniellenierenberg
All thalassemia patients need timely supply of safe blood for regular blood transfusion
There are 270 million Thalassemia patients in the world, yet India is called the Thalassemia capital because the country has the largest number of children suffering from this inherited blood disorder that causes the body to have less hemoglobin than normal.
More than 10,000 children are born in India with Thalassemia every year. According to World Health Organization, four million Indians are thalassemia carriers, while more than 1,00,000 are the actual patients battling the disease. Parents, who are usually asymptomatic, are the carriers of Thalassemia, and have a 25% chance of passing the disease to their children.
Even though thalassemia affects millions of people in the world, not many are aware about this condition. Early symptoms include fatigue, weakness, bone deformities (especially in the face), pale appearance or yellowish skin tone, slow growth rate, lowered immunity levels, and iron overload.
Due to financial barriers and lack of access to treatment, many young patients in India do not survive into adulthood. One of the major challenges is the lack of adequate pre-natal diagnosis facilities for Thalassemia, especially in rural areas. To manage the disease, patients need to take regular blood transfusions lifelong, along with iron chelation to treat iron overload in the body. These are very taxing procedures for young children that strain their health.
All Thalassemia patients need timely supply of safe blood for regular blood transfusion. It is not a permanent solution and is quite a painful process for a child. The annual requirement of packed red cells for Thalassemia patients is about 2 million units in India. Although patient organizations and regional blood banks have been working relentlessly towards fulfilling this requirement, the demand is significantly more than the current supply. Lot of families have to struggle month after month in making packed cells available for their children.
Repeated packed red cell transfusions lead to iron overload in patients. Excess iron gets deposited in organs like liver, heart and endocrine glands. This iron overload is usually the cause of death in the second or third decade of life. These patients need to be on medications to remove the extra iron from their bodies to ensure a normal life span for them. Yet, in spite of freely available drugs, less than 10% of Thalassemia patients are adequately chelated in India. Factors like ignorance, poor compliance and, more importantly, unaffordability are major reasons for poor chelation in Thalassemia patients.
Thalassemia is a multi-system problem. In addition to regular blood transfusion and iron chelation, the disease needs to be managed by a multidisciplinary team that should have hematologist, endocrinologist, cardiologist, nutritionist, nurse practitioner, etc. to provide holistic care. There are hardly any comprehensive centers for thalassemia care in India.
However, there is some good news too. With advances in the medical field, thalassemia major, once considered a cumbersome disease with lifelong blood transfusions, iron overload and limited lifespan, has seen a shift in the last decade with blood stem cell transplant, the only curative treatment option available for thalassemia.
Recent data shows 85-90% success rate of stem cell marrow transplantation in patients who have HLA matched stem cell donor. In a blood stem cell transplant, stem cells are collected from blood of the donors and transplanted into the thalassemia patient after their bone marrow has been destroyed by radiation or chemotherapy. Only 30% patients who need transplants have a fully HLA (Human Leukocyte Antigen) matched donor in their family, rest of them depend on an unrelated donor.
Patients and donors of Indian origin have unique HLA characteristics that are severely under-represented in the global database, which makes the probability of finding a suitable donor even more difficult. Indian patients mainly require an Indian tissue match. This calls for increased awareness and need to encourage people in India to register as a potential blood stem cell donor.
Registering as a potential donor is an easy process which can be done through online portal of a stem cell registry such as DKMS BMST Foundation India. Once you sign-up, you will receive a DIY home swab kit to take your cheek swab samples and send it back to the registry! Once an individual comes up as a match for a blood cancer patient, blood stem cells from the individual are obtained from the bloodstream using a procedure called peripheral blood stem cell collection, which is similar to a blood platelet donation..
Source: WHO, GLOBOCAN and Ministry of Health
(Dr. Nitin Agarwal, MD, Transfusion Medicine, HOD, Donor Request Management, DKMS BMST Foundation India)
Disclaimer: This content including advice provides generic information only. It is in no way a substitute for qualified medical opinion. Always consult a specialist or your own doctor for more information. NDTV does not claim responsibility for this information.
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World Thalassemia Day 2022: Why India Is The Thalassemia Capital Of The World - NDTV Doctor
Newsletter April 2022 – Progress in Cline’s cell lab and in the stem cell therapy field – Marketscreener.com
By daniellenierenberg
Spring has arrived in Gothenburg, and the Cline is excited to bring you some exciting news and updates from our team
The first stage of Ex-vivo testing completed
Early this month, Cline announced that the first stage of our ex-vivo experiments was carried out with encouraging performance. This newsletter will take a deeper look at what's happening in our labs and what these tests mean for StemCART.
These experiments, which began in January 2022, are an important milestone for the StemCART project and will push the project into the next development stage. In these tests, Cline has several aims; 1) demonstrate that the matrix developed by Cline successfully functions, 2) the successful differentiation of induced pluripotent stem cells (iPSCs) into functional chondrocytes (cartilage cells), and 3) to show induced healing of the injured cartilage tissue.
To achieve this, Cline has been collaborating with orthopedic surgeons and a hospital to collect cartilage tissue from patients undergoing surgery. Cline then takes this tissue from the hospital to our cell labs. At the lab we induce an artificial cartilage damage to mimic joint injuries before implanting the cells and matrix together at the injury site.
In this first stage of testing, the supporting matrix demonstrated the expected functionality in successfully fixing cells to the area of interest.
Read more about this in our latest press release or where Cline was recently featured on ORTHOWORLD.
Next steps for StemCART
The ex-vivo tests continues and Cline will carry out at least 24 further experiments in several stages. The results from these will be communicated after the completion of each stage. The upcoming stage of 10 experiments will test a higher cell concentration and focus on determining the functionality of the chondrocytes. Testing will also be expanded to include tissue of different cartilage origin, such as knee, shoulder, and hip.
StemCART's ultimate vision is as a cell-based Advanced Therapy Medical Product (ATMP) that will revolutionize the treatment of cartilage damage by providing patients with new functional cartilage and curing the condition, thus eliminating pain. StemCART provides several advantages over other therapy strategies such as autologous chondrocytes implantation and mesenchymal stem cells (MSCs) in that it provides reparative cartilage to the joint, and that an allogeneic cell source has much better scalability.
As part of the journey to this goal, Cline will continue preparing for in-human clinical trials, including scaling up production in a GMP facility together with partners, developing QA/QC methods, as well as the necessary safety testing and documentation for a clinical trial application. Cline has begun this work by evaluating different development and manufacturing options and engaging in regulatory pathway strategic planning activities.
Cline envisions out-licensing StemCART to a commercial partner following successful phase I trials. The process to identify and engage potential partners is ongoing, with the aim of generating interest in the commercialization of StemCART.
Exciting industry news and developments
2022 has already been an exciting year in the world of stem cell-based therapy and cartilage repair, showing the increasing interest and potential paradigm shift towards cell-based treatment. For example in the MSC segment, the Lund-based company Xintela recently began its first-in-human clinical trial for mesenchymal stem cells (MSC) in knee osteoarthritis (OA). Similarly, Cynata Therapeutics, working with iPSC-derived MSCs to treat knee OA, together with Fujifilm Cellular Dynamics, is currently conducting a large phase III trial. For more insights into the current landscape of cartilage repair treatments and current status of new cell-based treatments, you can read Cline Scientific's latest publication, "Insights into the present and future of cartilage regeneration and joint repair," available at https://www.mdpi.com/journal/ijms/special_issues/Cartilage_Repair.
Another leap forward for iPSC-derived tissue therapy is the conclusion of a world-first clinical trial, showing that implanting iPSC-derived corneal tissue into four nearly blind patients was safe and effective. The team from Osaka University used iPS cells to create the cornea tissue, which caused improvement of symptoms and eyesight and did not lead to any rejection or tumorigenicity.
Finally, in related orthopedic industry news, Bioventus acquired its partner CartiHeal for up to 450M USD. CartiHeal is an orthopedic device company that has developed the cartilage repair implant Agili-C, which was recently approved by the FDA. Agili-C is a cell-free scaffold implant for cartilage and osteochondral defects caused by either osteoarthritis or trauma.
We look forward to continuing to share Cline's journey in future newsletters!
Warmest regards,
The Cline Team
Click hereto subscribe to future newsletters and press releases.https://news.cision.com/cline/SubscriptionRegistrationDialog
Cline Scientific AB (publ) Telefon: 031-387 55 55Argongatan 2 C E-post: info@clinescientific.com431 53 MLNDAL Hemsida: http://www.clinescientific.com
About Cline ScientificCline Scientific develops advanced cancer diagnostics and regenerative medicine treatments. The company is working heavily with R&D through joint collaborations with pharmaceutical companies and academic researchers around the world. The focus is on projects in the cancer diagnostic and stem cell therapy fields since Clines nanotechnology here provides unmet solutions to critical challenges and functions. The unique patented surface nanotechnology is used in cell-based products and processes to drive projects within Life Science into and through the clinical phase.
https://mb.cision.com/Main/12114/3555837/1571081.pdf
(c) 2022 Cision. All rights reserved., source Press Releases - English
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Newsletter April 2022 - Progress in Cline's cell lab and in the stem cell therapy field - Marketscreener.com
Stem cell-based regenerative medicine – PMC
By daniellenierenberg
Stem Cell Investig. 2019; 6: 19.
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;
2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;
2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;
3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
1Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;
2Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran;
3Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Contributions: (I) Conception and design: E Fathi, R Farahzadi; (II) Administrative support: E Fathi, R Farahzadi; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: R Farahzadi, N Rajabzadeh; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
#These authors contributed equally to this work.
Received 2018 Nov 11; Accepted 2019 Mar 17.
Recent developments in the stem cell biology provided new hopes in treatment of diseases and disorders that yet cannot be treated. Stem cells have the potential to differentiate into various cell types in the body during age. These provide new cells for the body as it grows, and replace specialized cells that are damaged. Since mesenchymal stem cells (MSCs) can be easily harvested from the adipose tissue and can also be cultured and expanded in vitro they have become a good target for tissue regeneration. These cells have been widespread used for cell transplantation in animals and also for clinical trials in humans. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine as well as in regenerative medicine. Based on the studies in this field, MSCs found wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration etc.
Keywords: Mesenchymal stem cells (MSCs), animal model, cell-based therapy, regenerative medicine
Stem cells are one of the main cells of the human body that have ability to grow more than 200 types of body cells (1). Stem cells, as non-specialized cells, can be transformed into highly specialized cells in the body (2). In the other words, Stem cells are undifferentiated cells with self-renewal potential, differentiation into several types of cells and excessive proliferation (3). In the past, it was believed that stem cells can only differentiate into mature cells of the same organ. Today, there are many evidences to show that stem cells can differentiate into the other types of cell as well as ectoderm, mesoderm and endoderm. The numbers of stem cells are different in the tissues such as bone marrow, liver, heart, kidney, and etc. (3,4). Over the past 20 years, much attention has been paid to stem cell biology. Therefore, there was a profound increase in the understanding of its characteristics and the therapeutic potential for its application (5). Today, the utilization of these cells in experimental research and cell therapy represents in such disorders including hematological, skin regeneration and heart disease in both human and veterinary medicine (6).The history of stem cells dates back to the 1960s, when Friedenstein and colleagues isolated, cultured and differentiated to osteogenic cell lineage of bone marrow-derived cells from guinea pigs (7). This project created a new perspective on stem cell research. In the following, other researchers discovered that the bone marrow contains fibroblast-like cells with congenic potential in vitro, which were capable of forming colonies (CFU-F) (8). For over 60 years, transplantation of hematopoietic stem cells (HSCs) has been the major curative therapy for several genetic and hematological disorders (9). Almost in 1963, Till and McCulloch described a single progenitor cell type in the bone marrow which expand clonally and give rise to all lineages of hematopoietic cells. This research represented the first characterization of the HSCs (10). Also, the identification of mouse embryonic stem cells (ESCs) in 1981 revolutionized the study of developmental biology, and mice are now used extensively as one of the best option to study stem cell biology in mammals (11). Nevertheless, their application a model, have limitations in the regenerative medicine. But this model, relatively inexpensive and can be easily manipulated genetically (12). Failure to obtain a satisfactory result in the selection of many mouse models, to recapitulate particular human disease phenotypes, has forced researchers to investigate other animal species to be more probably predictive of humans (13). For this purpose, to study the genetic diseases, the pig has been currently determined as one the best option of a large animal model (14).
Stem cells, based on their differentiation ability, are classified into different cell types, including totipotent, pluripotent, multipotent, or unipotent. Also, another classification of these cells are based on the evolutionary stages, including embryonic, fetal, infant or umbilical cord blood and adult stem cells (15). shows an overview of stem cells classifications based on differentiation potency.
An overview of the stem cell classification. Totipotency: after fertilization, embryonic stem cells (ESCs) maintain the ability to form all three germ layers as well as extra-embryonic tissues or placental cells and are termed as totipotent. Pluripotency: these more specialized cells of the blastocyst stage maintain the ability to self-renew and differentiate into the three germ layers and down many lineages but do not form extra-embryonic tissues or placental cells. Multipotency: adult or somatic stem cells are undifferentiated cells found in postnatal tissues. These specialized cells are considered to be multipotent; with very limited ability to self-renew and are committed to lineage species.
Toti-potent cells have the potential for development to any type of cell found in the organism. In the other hand, the capacity of these cells to develop into the three primary germ cell layers of the embryo and into extra-embryonic tissues such as the placenta is remarkable (15).
The pluripotent stem cells are kind of stem cells with the potential for development to approximately all cell types. These cells contain ESCs and cells that are isolated from the mesoderm, endoderm and ectoderm germ layers that are organized in the beginning period of ESC differentiation (15).
The multipotent stem cells have less proliferative potential than the previous two groups and have ability to produce a variety of cells which limited to a germinal layer [such as mesenchymal stem cells (MSCs)] or just a specific cell line (such as HSCs). Adult stem cells are also often in this group. In the word, these cells have the ability to differentiate into a closely related family of cells (15).
Despite the increasing interest in totipotent and pluripotent stem cells, unipotent stem cells have not received the most attention in research. A unipotent stem cell is a cell that can create cells with only one lineage differentiation. Muscle stem cells are one of the example of this type of cell (15). The word uni is derivative from the Latin word unus meaning one. In adult tissues in comparison with other types of stem cells, these cells have the lowest differentiation potential. The unipotent stem cells could create one cell type, in the other word, these cells do not have the self-renewal property. Furthermore, despite their limited differentiation potential, these cells are still candidates for treatment of various diseases (16).
ESCs are self-renewing cells that derived from the inner cell mass of a blastocyst and give rise to all cells during human development. It is mentioned that these cells, including human embryonic cells, could be used as suitable, promising source for cell transplantation and regenerative medicine because of their unique ability to give rise to all somatic cell lineages (17). In the other words, ESCs, pluripotent cells that can differentiate to form the specialized of the various cell types of the body (18). Also, ESCs capture the imagination because they are immortal and have an almost unlimited developmental potential. Due to the ethical limitation on embryo sampling and culture, these cells are used less in research (19).
HSCs are multipotent cells that give rise to blood cells through the process of hematopoiesis (20). These cells reside in the bone marrow and replenish all adult hematopoietic lineages throughout the lifetime of the human and animal (21). Also, these cells can replenish missing or damaged components of the hematopoietic and immunologic system and can withstand freezing for many years (22).The mammalian hematopoietic system containing more than ten different mature cell types that HSCs are one of the most important members of this. The ability to self-renew and multi-potency is another specific feature of these cells (23).
Adult stem cells, as undifferentiated cells, are found in numerous tissues of the body after embryonic development. These cells multiple by cell division to regenerate damaged tissues (24). Recent studies have been shown that adult stem cells may have the ability to differentiate into cell types from various germ layers. For example, bone marrow stem cells which is derived from mesoderm, can differentiate into cell lineage derived mesoderm and endoderm such as into lung, liver, GI tract, skin, etc. (25). Another example of adult stem cells is neural stem cells (NSCs), which is derived from ectoderm and can be differentiate into another lineage such as mesoderm and endoderm (26). Therapeutic potential of adult stem cells in cell therapy and regenerative medicine has been proven (27).
For the first time in the late 1990s, CSCs were identified by John Dick in acute myeloid diseases. CSCs are cancerous cells that found within tumors or hematological cancers. Also, these cells have the characteristics of normal stem cells and can also give rise to all cell types found in a particular cancer sample (28). There is an increasing evidence supporting the CSCs hypothesis. Normal stem cells in an adult living creature are responsible for the repair and regeneration of damaged as well as aged tissues (29). Many investigations have reported that the capability of a tumor to propagate and proliferate relies on a small cellular subpopulation characterized by stem-like properties, named CSCs (30).
Embryonic connective tissue contains so-called mesenchymes, from which with very close interactions of endoderm and ectoderm all other connective and hematopoietic tissues originate, Whereas, MSCs do not differentiate into hematopoietic cell (31). In 1924, Alexander A. Maxi mow used comprehensive histological detection to identify a singular type of precursor cell within mesenchyme that develops into various types of blood cells (32). In general, MSCs are type of cells with potential of multi-lineage differentiation and self-renewal, which exist in many different kinds of tissues and organs such as adipose tissue, bone marrow, skin, peripheral blood, fallopian tube, cord blood, liver and lung et al. (4,5). Today, stem cells are used for different applications. In addition to using these cells in human therapy such as cell transplantation, cell engraftment etc. The use of stem cells in veterinary medicine has also been considered. The purpose of this review is to provide a summary of our current knowledge regarding the important and types of isolated stem cells from different sources of animal models such as horse, pig, goat, dog, rabbit, cat, rat, mice etc. In this regard, due to the widespread use and lot of attention of MSCs, in this review, we will elaborate on use of MSCs in veterinary medicine.
The isolation method, maintenance and culture condition of MSCs differs from the different tissues, these methods as well as characterization of MSCs described as (36). MSCs could be isolated from the various tissues such as adipose tissue, bone marrow, umbilical cord, amniotic fluid etc. (37).
Diagram for adipose tissue-derived mesenchymal stem cell isolation (3).
Diagram for bone marrow-derived MSCs isolation (33). MSC, mesenchymal stem cell.
Diagram for umbilical cord-derived MSCs isolation (34). MSC, mesenchymal stem cell.
Diagram for isolation of amniotic fluid stem cells (AFSCs) (35).
Diagram for MSCs characterization (35). MSC, mesenchymal stem cell.
The diversity of stem cell or MSCs sources and a wide aspect of potential applications of these cells cause to challenge for selecting an appropriate cell type for cell therapy (38). Various diseases in animals have been treated by cell-based therapy. However, there are immunity concerns regarding cell therapy using stem cells. Improving animal models and selecting suitable methods for engraftment and transplantation could help address these subjects, facilitating eventual use of stem cells in the clinic. Therefore, for this purpose, in this section of this review, we provide an overview of the current as well as previous studies for future development of animal models to facilitate the utilization of stem cells in regenerative medicine (14). Significant progress has been made in stem cells-based regenerative medicine, which enables researchers to treat those diseases which cannot be cured by conventional medicines. The unlimited self-renewal and multi-lineage differentiation potential to other types of cells causes stem cells to be frontier in regenerative medicine (24). More researches in regenerative medicine have been focused on human cells including embryonic as well as adult stem cells or maybe somatic cells. Today there are versions of embryo-derived stem cells that have been reprogrammed from adult cells under the title of pluripotent cells (39). Stem cell therapy has been developed in the last decade. Nevertheless, obstacles including unwanted side effects due to the migration of transplanted cells as well as poor cell survival have remained unresolved. In order to overcome these problems, cell therapy has been introduced using biocompatible and biodegradable biomaterials to reduce cell loss and long-term in vitro retention of stem cells.
Currently in clinical trials, these biomaterials are widely used in drug and cell-delivery systems, regenerative medicine and tissue engineering in which to prevent the long-term survival of foreign substances in the body the release of cells are controlled (40).
Today, the incidence and prevalence of heart failure in human societies is a major and increasing problem that unfortunately has a poor prognosis. For decades, MSCs have been used for cardiovascular regenerative therapy as one of the potential therapeutic agents (41). Dhein et al. [2006] found that autologous bone marrow-derived mesenchymal stem cells (BMSCs) transplantation improves cardiac function in non-ischemic cardiomyopathy in a rabbit model. In one study, Davies et al. [2010] reported that transplantation of cord blood stem cells in ovine model of heart failure, enhanced the function of heart through improvement of right ventricular mass, both systolic and diastolic right heart function (42). In another study, Nagaya et al. [2005] found that MSCs dilated cardiomyopathy (DCM), possibly by inducing angiogenesis and preventing cardial fibrosis. MSCs have a tremendous beneficial effect in cell transplantation including in differentiating cardiomyocytes, vascular endothelial cells, and providing anti-apoptotic as well angiogenic mediators (43). Roura et al. [2015] shown that umbilical cord blood mesenchymal stem cells (UCBMSCs) are envisioned as attractive therapeutic candidates against human disorders progressing with vascular deficit (44). Ammar et al., [2015] compared BMSCs with adipose tissue-derived MSCs (ADSCs). It was demonstrated that both BMSCs and ADSCs were equally effective in mitigating doxorubicin-induced cardiac dysfunction through decreasing collagen deposition and promoting angiogenesis (45).
There are many advantages of small animal models usage in cardiovascular research compared with large animal models. Small model of animals has a short life span, which allow the researchers to follow the natural history of the disease at an accelerated pace. Some advantages and disadvantages are listed in (46).
Despite of the small animal model, large animal models are suitable models for studies of human diseases. Some advantages and disadvantages of using large animal models in a study protocol planning was elaborated in (47).
Chronic wound is one of the most common problem and causes significant distress to patients (48). Among the types of tissues that stem cells derived it, dental tissuederived MSCs provide good sources of cytokines and growth factors that promote wound healing. The results of previous studies showed that stem cells derived deciduous teeth of the horse might be a novel approach for wound care and might be applied in clinical treatment of non-healing wounds (49). However, the treatment with stem cells derived deciduous teeth needs more research to understand the underlying mechanisms of effective growth factors which contribute to the wound healing processes (50). This preliminary investigation suggests that deciduous teeth-derived stem cells have the potential to promote wound healing in rabbit excisional wound models (49). In the another study, Lin et al. [2013] worked on the mouse animal model and showed that ADSCs present a potentially viable matrix for full-thickness defect wound healing (51).
Many studies have been done on dental reconstruction with MSCs. In one study, Khorsand et al. [2013] reported that dental pulp-derived stem cells (DPSCs) could promote periodontal regeneration in canine model. Also, it was shown that canine DPSCs were successfully isolated and had the rapid proliferation and multi-lineage differentiation capacity (52). Other application of dental-derived stem cells is shown in .
Diagram for application of dental stem cell in dentistry/regenerative medicine (53).
As noted above, stem cells have different therapeutic applications and self-renewal capability. These cells can also differentiate into the different cell types. There is now a great hope that stem cells can be used to treat diseases such as Alzheimer, Parkinson and other serious diseases. In stem cell-based therapy, ESCs are essentially targeted to differentiate into functional neural cells. Today, a specific category of stem cells called induced pluripotent stem (iPS) cells are being used and tested to generate functional dopamine neurons for treating Parkinson's disease of a rat animal model. In addition, NSC as well as MSCs are being used in neurodegenerative disorder therapies for Alzheimers disease, Parkinsons disease, and stroke (54). Previous studies have shown that BMSCs could reduce brain amyloid deposition and accelerate the activation of microglia in an acutely induced Alzheimers disease in mouse animal model. Lee et al. [2009] reported that BMSCs can increase the number of activated microglia, which effective therapeutic vehicle to reduce A deposits in AD patients (55). In confirmation of previous study, Liu et al. [2015] showed that transplantation of BMSCs in brain of mouse model of Alzheimers disease cause to decrease in amyloid beta deposition, increase in brain-derived neurotrophic factor (BDNF) levels and improvements in social recognition (56). In addition of BMSCs, NSCs have been proposed as tools for treating neurodegeneration disease because of their capability to create an appropriate cell types which transplanted. kerud et al. [2001] demonstrated that NSCs efficiently express high level of glial cell line-derived neurotrophic factor (GDNF) in vivo, suggesting a use of these cells in the treatment of neurodegenerative disorders, including Parkinsons disease (57). In the following, Venkataramana et al. [2010] transplanted BMSCs into the sub lateral ventricular zones of seven Parkinsons disease patients and reported encouraging results (58).
The human body is fortified with specialized cells named MSCs, which has the ability to self-renew and differentiate into various cell types including, adipocyte, osteocyte, chondrocyte, neurons etc. In addition to mentioned properties, these cells can be easily isolated, safely transplanted to injured sites and have the immune regulatory properties. Numerous in vitro and in vivo studies in animal models have successfully demonstrated the potential of MSCs for various diseases; however, the clinical outcomes are not very encouraging. Based on the studies in the field of stem cells, MSCs find wide application in treatment of diseases, such as heart failure, wound healing, tooth regeneration and etc. In addition, these cells are particularly important in the treatment of the sub-branch neurodegenerative diseases like Alzheimer and Parkinson.
The authors wish to thank staff of the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Funding: The project described was supported by Grant Number IR.TBZMED.REC.1396.1218 from the Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflicts of Interest: The authors have no conflicts of interest to declare.
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Stem cell-based regenerative medicine - PMC
Global Stem Cell Market To Be Driven By Increasing Activities To Use Stem Cells In Regenerative Medicines In The Forecast Period Of 2022-2027 …
By daniellenierenberg
The new report by Expert Market Research titled, Global Stem Cell Market Report and Forecast 2022-2027, gives an in-depth analysis of the globalstem cell market, assessing the market based on its segments like types, treatment types, applications and major regions. The report tracks the latest trends in the industry and studies their impact on the overall market. It also assesses the market dynamics, covering the key demand and price indicators, along with analysing the market based on the SWOT and Porters Five Forces models.
Request a free sample copy in PDF or view the report summary@https://www.expertmarketresearch.com/reports/stem-cell-market/requestsample
The key highlights of the report include:
Market Overview (2017-2027)
The stem cell business is growing due to an increase in activities to use stem cells in regenerative treatments due to their medicinal qualities. The increasing use of human-induced pluripotent stem cells (iPSCs) for the treatment of hereditary cardiac difficulties, neurological illnesses, and genetic diseases such as recessive dystrophic epidermolysis bullosa (RBED) is driving the market forward.
Furthermore, because human-induced pluripotent stem cells (iPSCs) may reverse immunosuppression, they serve as a major source of cells for auto logic stem cell therapy, boosting the industrys expansion. Furthermore, the rising incentives provided by major businesses to deliver breakthrough stem cell therapies, as well as the increased use of modern resources and techniques in research and development activities (R&D), are propelling the stem cell market forward.
Because of increased research and development (R&D) in the United States and Canada, North America accounts for a significant portion of the overall stem cell business. Furthermore, the increased frequency of non-communicable chronic diseases such as cancer and Parkinsons disease, among others, is boosting the use of stem cell therapy, boosting the industrys growth. Furthermore, the regions stronghealthcaresector is improving access to innovative cell therapy treatments, assisting the regional stem cell industrys expansion. Aside from that, due to the rising use of regenerative treatments, the Asia Pacific area is predicted to rise rapidly. Furthermore, rising clinical trials are assisting market expansion due to low labour costs and the availability of raw materials in the region, contributing considerably to overall industry growth.
Industry Definition and Major Segments
A stem cell is a type of cell that has the ability to develop into a variety of cells, including brain cells and muscle cells. It can also help to repairtissuesthat have been injured. Because stem cells have the potential to treat a variety of non-communicable and chronic diseases, including Alzheimers and diabetes, theyre being used in medical and biotechnological research to repair tissue damage caused by diseases.
Explore the full report with the table of contents@https://www.expertmarketresearch.com/reports/stem-cell-market
The major product types of stem cell are:
The market can be broadly categorised on the basis of its treatment types into:
Based on applications, the market is divided into:
The EMR report looks into the regional markets of stem cell-like:
Market Trends
The market is expected to rise due to increased research activity in regenerative medicine and biotechnology to personalise stem cell therapy. The usage of stem cells is predicted to increase as the need for treatment of common disorders, such as age-related macular degeneration (AMD), grows among the growing geriatric population. Due to multiple error bars during research operations, it becomes extremely difficult to characterise cell products because each cell has unique properties. As a result, the integration of cutting-edge technologies such as artificial intelligence (AI), blockchain, and machine learning is accelerating. Artificial intelligence (AI) is being used to analyse images quickly, forecast cell functions, and classify tissues in order to identify cell products, which is expected to boost the market growth.
With the rising frequency of cancer and cancer-related research initiatives, blockchain technology is increasingly being used to collect and assimilate data in order to improve access to clinical outcomes and the latest advances. Blockchain can also help with data storage for patients while improving the cost-effectiveness of cord-blood banking for advanced research and development (R&D) purposes. In addition, the use of machine learning techniques to analyse photos and infer the relationship between cellular features is boosting the market growth. The increased interest in understanding cellular processes and identifying critical processes using deep learning is expected to move the stem cell business forward.
Latest News on Global Stem Cell Market@https://www.expertmarketresearch.com/pressrelease/global-stem-cell-market
Key Market Players
The major players in the market are Pluristem Therapeutics Inc., Thermo Fisher Scientific Inc., Cellular Engineering Technologies, Merck KGaA, Becton, Dickinson and Company, and STEMCELL Technologies Inc The report covers the market shares, capacities, plant turnarounds, expansions, investments and mergers and acquisitions, among other latest developments of these market players.
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Global Stem Cell Market To Be Driven By Increasing Activities To Use Stem Cells In Regenerative Medicines In The Forecast Period Of 2022-2027 ...
First all-private astronaut team aboard space station heads for splashdown – KFGO
By daniellenierenberg
By Steve Gorman
(Reuters) The first all-private astronaut crew to fly aboard the International Space Station (ISS) headed for splashdown Monday off the coast of Florida, wrapping up a two-week mission that NASA has touted as a landmark in commercial spaceflight.
A SpaceX Crew Dragon capsule carrying the four-man team of Houston-based startup Axiom Space Inc began its return flight about 9 p.m. EDT Sunday (0100 Monday GMT) as it undocked from the space station orbiting about 250 miles (420 km) above Earth.
The Crew Dragon was expected to parachute into the Atlantic around 1 p.m. EDT on Monday (1700 GMT), capping a 16-hour ride home from orbit that had been postponed for several days because of unfavorable weather.
The multinational Axiom team was led by Spanish-born retired NASA astronaut Michael Lopez-Alegria, 63, the companys vice president for business development. His second-in-command was Larry Connor, 72, a technology entrepreneur and aerobatics aviator from Ohio designated the mission pilot.
Joining them as mission specialists were investor-philanthropist and former Israeli fighter pilot Eytan Stibbe, 64, and Canadian businessman and philanthropist Mark Pathy, 52.
Launched from NASAs Kennedy Space Center on April 8, they spent 15 days aboard the space station with the seven regular, government-paid ISS crew members: three American astronauts, a German astronaut and three Russian cosmonauts.
The ISS has hosted several wealthy space tourists from time to time over the years.
But the Axiom quartet was the first all-commercial team ever welcomed to the space station as working astronauts, bringing with them 25 science and biomedical experiments to conduct in orbit. The package included research on brain health, cardiac stem cells, cancer and aging, as well as a technology demonstration to produce optics using the surface tension of fluids in microgravity.
Axiom, NASA and SpaceX have hailed the mission as a milestone in the expansion of privately funded space-based commerce, constituting what industry insiders call the low-Earth orbit economy, or LEO economy for short.
It was the sixth human spaceflight for SpaceX in nearly two years, following four NASA astronaut missions to the ISS and the Inspiration 4 flight in September that sent an all-private crew into Earth orbit for the first time, though not to the space station.
SpaceX, the private rocket company founded by Tesla Inc electric carmaker CEO Elon Musk, has been hired to fly three more Axiom astronaut missions to ISS over the next two years. The price tag for such outings is high.
Axiom charges customers $50 million to $60 million per seat, according to Mo Islam, head of research for the investment firm Republic Capital, which holds stakes in both Axiom and SpaceX.
Axiom also was selected by NASA in 2020 to build a new commercial addition to the space station, which a U.S.-Russian-led consortium of 15 countries has operated for more than two decades. Plans call for the Axiom segment to eventually replace the ISS when the rest of the station is retired around 2030.
(Reporting by Steve Gorman in Los Angeles. Editing by Gerry Doyle)
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First all-private astronaut team aboard space station heads for splashdown - KFGO