Mesoblast Operational and Financial Highlights for Quarter Ended March 31, 2022 Mesoblast Operational and Financial Highlights for Quarter Ended March 31, 2022
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Appendix 4C Quarterly Activity Report
Basel, 29 April 2022 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced new three-year data from the FIREFISH study, including one-year data from the open label extension, reinforcing the long-term efficacy and safety of Evrysdi® (risdiplam) in infants with symptomatic Type 1 spinal muscular atrophy (SMA). The data showed an estimated 91% of infants (n=58) treated with Evrysdi were alive after three years of treatment. The Evrysdi-treated infants continued to improve or maintain motor functions, including the ability to swallow, sit without support, stand with support and walk while holding on, between two and three years of treatment. Without treatment, children with Type 1 SMA are never able to sit without support. The study also showed overall continued reductions in serious adverse events (SAEs) and hospitalisations over time.
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Bone Therapeutics announces 2021 full year results
LONDON, April 29, 2022 (GLOBE NEWSWIRE) -- Dear shareholders, friends,
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Letter to shareholders from CLINUVEL’s CEO
Ad hoc announcement pursuant to Art. 53 LR
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Santhera will Publish its 2021 Annual Report by June 3, 2022, and Hold its Annual General Meeting on June 29, 2022
Summary: Researchers have uncovered a new type of cell death that occurs in the guts of flies. The process, called erebosis, is believed to play a role in gut metabolism.
Source: RIKEN
A research group led by Sa Kan Yoo at the RIKEN Center for Biosystems Dynamics Research (BDR) has discovered a completely unknown type of cell death that takes place in the guts of the common fruit fly.
The new process, coined erebosis by the researchers is thought to play a role in gut metabolism. The findings necessitate a revision of the conventional concept of cell death, and at the same time, overturn the previously established theory of tissue homeostasis in the gut.
The study was published April 25 in scientific journalPLOS Biology.
Like the skin, cells that make up the intestines are constantly dying and being replaced by new cells. This process, called turnover, helps maintain the balance, or homeostasis, between tissue growth and tissue renewal. The conventional theory for turnover in the intestines is that aging or damaged cells die through a process called apoptosis.
Also called programmed cell death, apoptosis is one of three types of cell death that are currently recognized.
The new research calls this assumption into question, providing evidence for a second type of programmed cell death that could be specific to the intestines.
As is often the case, this discovery occurred by accident. The researchers were studying a fruit fly version of ANCE, an enzyme that helps lower blood pressure. They noticed thatAnceexpression in the fly gut was patchy, and that the cells that contained it had strange characteristics.
We found that Ance labels some weird cells in the fruit fly gut, says Yoo.
But it took a long time for us to figure out that these weird cells were actually dying. They found that the strange cells were dark, lacking nuclear membranes, mitochondria, and cytoskeletons, and sometimes even DNA and other cellular items that are needed for cells to stay alive.
The process was so gradual and unlike the more sudden and explosive cell death seen in apoptosis, that they realized it might be something new.
Because the Ance-positive cells were often near where new cells are born in the gut, they theorized that the new type of cell death is related to turnover in the intestines.
They tentatively named the process erebosis, based on the Greek erebos meaning darkness, because the dying cells looked so dark under the microscope.
To prove erebosis is a new type of cell death, the researchers conducted several tests. First, experimentally stopping apoptosis did not prevent gut homeostasis. This meant that cell turnover in the gut, including cell death, can proceed without apoptosis.
Second, the dying cells did not show any of the molecular markers for apoptosis or the other two types of known cell death. Cells in late-stage erebosis did show a general marker for cell death related to degraded DNA.
Detailed examination of the cells in which erebosis was occurring revealed that they were located near clusters of gut stem cells. This is good evidence erebotic cells are replaced by newly differentiated gut cells during turnover.
Ironically, the enzyme that led to this discovery does not seem to be directly involved in the process, as knocking down or overexpressing Ance did not affect turnover or erebosis. Therefore, the next step is work out the detailed molecular events that allow erebosis and cell turnover in the fly gut.
I feel our results have the potential to be a seminal finding. Personally, this work is the most groundbreaking research I have ever done in my life. says Yoo, We are keenly interested in whether erbosis exists in the human gut as well as in fruit flies.
Author: Masataka Sasabe Source: RIKEN Contact: Masataka Sasabe RIKEN Image: The image is credited to RIKEN
Original Research: Open access. Erebosis, a new cell death mechanism during homeostatic turnover of gut enterocytes by Sa Kan Yoo et al. PLOS Biology
Abstract
Erebosis, a new cell death mechanism during homeostatic turnover of gut enterocytes
Many adult tissues are composed of differentiated cells and stem cells, each working in a coordinated manner to maintain tissue homeostasis during physiological cell turnover. Old differentiated cells are believed to typically die by apoptosis.
Here, we discovered a previously uncharacterized, new phenomenon, which we name erebosis based on the ancient Greek word erebos (complete darkness), in the gut enterocytes of adultDrosophila. Cells that undergo erebosis lose cytoskeleton, cell adhesion, organelles and fluorescent proteins, but accumulate Angiotensin-converting enzyme (Ance).
Their nuclei become flat and occasionally difficult to detect.
Erebotic cells do not have characteristic features of apoptosis, necrosis, or autophagic cell death. Inhibition of apoptosis prevents neither the gut cell turnover nor erebosis.
We hypothesize that erebosis is a cell death mechanism for the enterocyte flux to mediate tissue homeostasis in the gut.
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A New Type of Cell Death Discovered in Fly Guts - Neuroscience News
Embryonic mitosis stem cells colony tissue section magnified in microscope, 3D illustration. ( Eduard Muzhevskyi - stock.adobe.com)
Stem cells are key building blocks for the human body. At the start of life, they divide over and over again to create a fully developed baby from an embryo. Many individuals now even turn to services that store and preserve umbilical cords should a person ever be in need.
Stem cells have the potential to develop into different types of cells in the body, serving as a repair system of sorts for damaged or lost cells. In recent decades, scientists have shown the miraculous ways of medicine through stem cell treatments.
So just how are doctors using stem cells to treat and help heal people battling various ailments? Heres a look at five studies published on StudyFinds that demonstrate the wondrous ways of stem cell treatments.
A heart condition called dilated cardiomyopathy, or DCM, weakens muscles of the ventricles, which causes heart failure and often death in children. Currently, the only cure is a heart transplant, which can take long periods of time to find an acceptable donor and increases the risk of rejection of the donor tissue. One study finds that stem cell therapy could help DCM patients survive longer while awaiting a transplant or potentially eliminate the need for a new heart entirely.
Cardiac stem cells called cardiosphere-derived cells (CDCs) have proven to be effective at treating certain heart conditions. The CDCs grow into tissue cells of the heart and can counter the effects of DCM. To test the safety of the CDC therapy, a team of scientists at Okayama University in Japan demonstrated the efficacy of CDCs in tissue damaged from DCM. For the study, DCM symptoms were induced in pigs, after which CDCs were administered in various doses for treatment. In a control group, some pigs were given a placebo.
Results showed thickening of the heart muscle in pigs who were given the stem cell treatment. This allows increased blood flowto the rest of the body, thereby effectively repairing the damaged tissue. Due to the dosage used in animal trials, researchers could estimate the proper dosage for human trials.
The first of these included 5 younger patients who were diagnosed with DCM. Injections of CDCs resulted inbetter heart function without any serious side effects. Thus, scientists believe this type of treatment could minimize the need for heart transplants and allow DCM patients to have normal lives.
READ MORE: Stem cell treatment shows promise as treatment for rare heart condition in children
Although their use is sometimes controversial, scientists often look at stem cells as a potential miracle cure for many conditions. One study finds stem cells from a babys umbilical cord may save the most at risk of dying from COVID-19. A treatment derived from non-altered versions of these stem cells significantly improves the survival rate among coronavirus patients already on a ventilator.
In a double-blind, controlled, randomized study, 40 adultpatients in intensive careand on a ventilator received the treatment intravenously. The infusions contained stem cells coming from the connective tissue of a human umbilical cord. Half of the patients received infusions not containing stem cells to serve as a control group.
Results reveal survival rates climbed by 2.5 times among patients receiving stem cells. Those with a pre-existing health problem, making them high-risk for COVID, saw their changes of beating coronavirus jump by 4.5 times. Moreover, the study says the stem cell infusions did not cause any life-threatening complications or allergic reactions.
READ MORE: Stem cells from a babys umbilical cord doubles survival chances among COVID patients
In the fight against heart disease, a new super-weapon is now even closer to deployment, and its capabilities are turning out to be beyond expectations. A study aimed at combating heart disease finds that stem cells are not only showing promise in treating heart failure, but in rats are actually reversing problems associated with old age.
The specific type of stem cells used in the study are cardiosphere-derived cells, or CDCs. While the latest research involving CDCs indicates possibilities that have previously been in the realm of science fiction, the scientists leading the charge urge restraint in face of the excitement.
Nevertheless, the latest results of stem cell infusions in rats are startling. Not only did rats that received the CDCs experience improved heart function, they also had lengthened heart cell telomeres. Moreover, the rats that received the treatment also had their exercise capacity increase by about 20 percent. They also regrew hair faster than rats that didnt receive the cells.
Still, the doctors and scientists working to push the frontier of medicine forward are very optimistic about the real possibilities of the therapy. Researchers of the study said they are also studying the use of stem cells in treating patients with Duchenne muscular dystrophy and patients with heart failure with preserved ejection fraction, a condition that affects more than 50 percent of all heart failure patients.
READ MORE: Study: Cardiac stem cell injections reverse effects of aging
A new biomaterial can help regenerate tissue in people dealing with chronic lower back pain and spinal issues. A recent study finds the secret to this breakthrough therapy is all in the hiPS. Not thosehips, but human induced pluripotent stem cells.
The study explains that a common cause of lower back pain is the degeneration of intervertebral discs (IVDs). These discs sit between the vertebrae in the spine and help give the spinal column its flexibility. Severe IVD degeneration eventually leads to spinal deformity without treatment. In this study, scientists used cartilage tissue derived from stem cells to build back lost IVDs in lab rats.
Study authors used induced pluripotent stem cells (iPSCs) during their experiments. Importantly, scientists are capable of turning iPSCs into chondrocytes cells that produce and maintain cartilage. Previous studies have successfully used this same method to treat cartilage defects in animals. In the new study, researchers created human iPSC-derived cartilaginous tissue (hiPS-Cart) that they implanted into rats with no NP cells in their intervertebral discs.
Findings reveal that the hiPS-Cart implanted in the rats was able to survive and be maintained. IVD and vertebral bone degeneration were prevented. The researchers also assessed the mechanics and found that hiPS-Cart was able to revert these properties to similar levels observed in the control rats.
READ MORE: Stem cell cure for lower back pain is all in the hiPS
Stem cells taken from deceased patients may also help in creating a cure for blindness. Retina cells from a corpse continue to survive after being transplanted into the eyes of monkeys, scientists say.
RPE dysfunction is a leading cause of blindness, including causing disorders likemacular degeneration, which affects around 200 million people worldwide. Now, for the first time, scientists have successfully produced retina cells in monkeys using human stem cells. Human cadaver donor-derived cells can be safely transplanted underneath the retina and replace host function, and therefore may be a promising source for rescuing visionin patients with retina diseases.
For the study, researchers transplanted stem cells from the eyes of donated bodies under the monkeys macula, the central part of the retina. Following surgery, the transplanted patches remained stable for at least three months without any serious side-effects. The RPE created by the human stem cells partially took over from the old retina cells. In addition, this could successfully support the eyes light receptorswithout causing retinal scarring.
These unique cells could serve as an unlimited resource of human RPE, whichmay restore sightfor millions of people around the world. The scientists caution that they will need to conduct more research to see how the procedure works with human transplant patients. Human trials are still a long way off.
READ MORE: Eye stem cells transplanted from corpses to live patients could cure blindness
For more information on each of these stem cell treatments, you can refer to the READ MORE links in between each section.
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Stem Cell Magic: 5 Promising Treatments For Major Medical Conditions - Study Finds
Rey Mysterio has shared that he and his son Dominik are both undergoing stem cell treatment. Mysterio hopes that it will allow him to live pain-free and perform like he was 25 again.
Rey Mysterio has not been seen on WWE TV since the Raw following WrestleMania 38 when he and Dominik were attacked by a debuting Veer Mahaan. The assault came after Dominik had been quickly defeated by The Miz. With Dominik gathering himself in the ring, Veer arrived on the scene to hand out some more punishment. He threw Rey to one side before locking in a modified Camel Clutch on Dominik to leave him laying.
This led to the announcement of a match between Rey Mysterio and Veer the following week, April 11th. However, the elder Mysterio was missing from the show, with Veer instead taking on and defeating Dominik in short order.
Following his absence, Dave Meltzer reported on Wrestling Observer Radio that Mysterio was suffering from an undisclosed medical issue, but could be back in a matter of weeks.
Hes a medical issue, Its not false advertising or they changed their mind. It was he was unavailable tonight. So they put Dominik in the place and Dominik just got destroyed. So, they could probably do Rey in a week or two.
Now, Rey Mysterio has taken to Instagram to tell fans that he and Dominik have both undergone stem cell treatment.
My boy @dominik_35 and I started our #StemCell treatment on Monday and today we had an incredible reception too the injections.
Big thanks too the homie David y gracias al Dr. Vallejo por cuidarnos alTiene buena mano Doc!! #CPI
On his IV bag, Mysterio has written that he hopes the treatment will let him work pain-free and perform like he was 25 years old again.
God bless these stem cells so they can do work and repair my body so I can live pain-free and perform like I was 25 again. RM 619.
At the time of writing, it is unknown when Mysterio will return to WWE TV.
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Rey Mysterio Reveals He Has Started Stem Cell Treatment - Inside The Ropes
No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P= .0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P =.017) mL/minute. XQ summary score decreased by 22.6 units (P= .0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P= .0013), sticky saliva 23.3 (P= .0015), and swallowing 10.0 (P= .0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.
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
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Cline Scientific AB (publ) Telefon: 031-387 55 55 Argongatan 2 C E-post: info@clinescientific.com 431 53 MLNDAL Hemsida: http://www.clinescientific.com
About Cline Scientific Cline 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
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Newsletter April 2022 - Progress in Cline's cell lab and in the stem cell therapy field - Marketscreener.com