Monthly Archives

October 2020

Home / October 2020
News

Stem cell sheets harvested in just two days — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

Stem cells are cell factories that constantly divide themselves to create new cells. Implanting stem cells in damaged organs can regenerate new tissues. Cell sheet engineering, which allows stem cells to be transplanted into damaged areas in the form of sheets made up of only cells, completely eliminates immune rejection caused by external substances and encourages tissue regeneration. A research team led by POSTECH recently succeeded in drastically reducing the harvest period of such stem cell sheets.

A joint research team comprised of Professor Dong Sung Kim and researcher Andrew Choi of POSTECH’s Department of Mechanical Engineering and Dr. InHyeok Rhyou and Dr. Ji-Ho Lee of the Department of Orthopedic Surgery at Pohang Semyung Christianity Hospital has significantly reduced the total harvest period of a stem cell sheet to two days. The nanotopography of poly(N-isopropylacrylamide) (PNIPAAm), which abruptly changes its roughness depending on temperature, allows harvesting of cell sheets that consist of mesenchymal stem cells derived from human bone marrow. Considering that it takes one week on average to make stem cells into sheets using the existing techniques developed so far, this is the shortest harvest time on record. These research findings were published as a cover paper in the latest issue of Biomaterials Science, an international journal in the biomaterials field.

Professor Kim’s research team focused on PNIPAAm, a polymer that either combines with water or averts it depending on the temperature. In previous studies, PNIPAAm has been introduced as a coating material for cell culture platform to harvest cell sheets, but the range of utilization had been hampered due to the limited types of cells that can be made into sheets. For the first time in 2019, the research team developed a technology of easily regulating the roughness of 3D bulk PNIPAAm and has stably produced various types of cells into sheets.

The study conducted this time focused on making stem cells — that are effective in tissue regeneration — into sheets in a short time in order to increase their direct utility. The team achieved this by applying an isotropic pattern of nanopores measuring 400 nanometers (nm, 1 billionth of a meter) on the surface of a 3D bulk PNIPAAm. As a result, not only did the formation and maturity of human bone marrow-derived mesenchymal stem cells on the nanotopography of bulk PNIPAAm accelerate, but the surface roughness of bulk PNIPAAm at room temperature below the lower critical solution temperature (LCST) was also rapidly increased, effectively inducing the detachment of cell sheets. This in turn enabled the rapid harvesting of human bone marrow-derived mesenchymal stem cell sheets.

“At least five days are needed to harvest stem cell sheets reported through previous researches,” commented Andrew Choi, the ” author of the paper. “We can now harvest them in just two days with the PNIPAAm nanotopography developed this time.”

“We have significantly shortened the harvest time by introducing nanotopography on the surface of the 3D bulk PNIPAAm to produce mature stem cell sheets for the first time in the world,” remarked Professor Dong Sung Kim who led the study. He added, “We have opened up the possibility of applying the sheets directly to patients in the future.”

The research was conducted with the support from Basic Research Program (Mid-career Researcher Program) and the Biomedical Technology Development Program of the National Research Foundation and the Ministry of Science and ICT of Korea.

Story Source:

Materials provided by Pohang University of Science & Technology (POSTECH). Note: Content may be edited for style and length.

Source link

News

Coupling antibiotics with stem cells to fight off bone infections — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

Bone infections caused by implants are difficult to treat and usually require a prolonged course of antibiotic treatment. In a new study, researchers from Kanazawa University discovered that implant-related bone infections can be effectively treated with a combinational treatment consisting of antibiotics and antibiotic-laden stem cells.

Bone fractures often require implants for stabilization and effective healing of the broken bone. However, implants can cause serious bone infections, such as osteomyelitis, that can only be managed with a prolonged antibiotic treatment. This in turn bears the risk of contributing to the development of antibiotic-resistant bacteria. While major efforts are currently underway to develop new antibiotics that cover these antibiotic-resistant bacteria, a different path has been to study the antibiotic effects of stem cells. One type is the so-called mesenchymal stem cells that naturally reside in the bone marrow and adipose tissue, among others, and that have been shown to possess antimicrobial properties.

“Adipose-derived stem cells, or ADSCs, have the distinct advantage of being abundant in subcutaneous adipose tissues and can thus be easily harvested,” says the corresponding author of the study Tamon Kabata. “The goal of our study was to investigate the therapeutic effects of ADSCs in combination with the antibiotic ciprofloxacin in an animal model of implant-related bone infection.”

To achieve their goal, the researchers first focused on the effects of ciprofloxacin on ADSCs and found an efficient, time-dependent loading of ADSCs with the antibiotic in the first 24 hours with no adverse effects of ciprofloxacin on the function or viability of the stem cells. The researchers then tested the antimicrobial activity of the antibiotic-loaded ADSCs in vitro (in a tube) and found that they effectively decreased the growth of the bacterium S. aureus, which is also the main microbe causing bone implant-related infections.

But could this novel approach also mitigate implant-related infection in a living organism? The researchers tested this on rats, who received bone implants using screws coated with S. aureus bacteria. The rats developed osteomyelitis 7 days after surgery. Then, the researchers administered one of the following to the animals: ADSCs loaded with ciprofloxacin, ADSCs alone, ciprofloxacin alone, or no treatment at all. Because osteomyelitis can lead to soft tissue swelling and abscess formation at the site of the infection, the researchers quantified the extent of the disease in the animals and found that only ADSCs loaded with ciprofloxacin presented as an effective treatment. Using the imaging modality micro-computed tomography to visualize the affected bones, the researchers further found that ADSC-loaded ciprofloxacin decreased the appearance of osteolysis, or bone degradation, which is not only important for bone health, but also for the stability of the implant.

“These are striking results that show how ADSCs can efficiently be loaded with antibiotics to exert a strong antimicrobial effect. Our findings suggest a potential novel therapy for implant-associated osteomyelitis, for which conventional treatment with only antibiotics is usually insufficient,” says Kabata.

Story Source:

Materials provided by Kanazawa University. Note: Content may be edited for style and length.

Source link

News

A small switch with a big impact — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

T cells play a key role in the human immune system. They are capable of distinguishing diseased or foreign tissue from the body’s own, healthy tissue with great accuracy; they are capable of triggering the actions necessary to fight off the troublemakers. The details of this immune response are manifold and the individual steps are not yet fully understood.

Scientists of the universities of Würzburg and Mainz have now figured out new details of these processes, showing that tiny point mutations in a gene can modify T cells to be less aggressive. This could be an advantage after stem cell transplantation which includes T-cell transfusion in order to keep a number of severe side effects in check. The researchers have now published the results of their study in the Journal of Experimental Medicine. The study is led by Dr Friederike Berberich-Siebelt, head of the “Molecular and cellular immunology” research group at the Institute of Pathology of the University of Würzburg.

A protein family with multiple tasks

When T cells detect foreign or altered tissue, such as an infected or tumour tissue, this usually happens through the receptors on their cell surface. These T-cell receptors then send signals into the cell interior, initiating a response. In a first step, they activate a special family of transcription factors — scientifically called NFAT for nuclear factor of activated T-cells. The NFATs then bind to the DNA in the cell nucleus and trigger also the production of cytokines such as interleukin-2.

NFAT is composed of many family members which may have overlapping tasks or assume completely different functions. But that’s not all: Like many other proteins in the cell, they can still be modified after their synthesis to customize their function. The recently published study focuses on one specific modification of the NFATc1 “family member” which is called sumoylation.

Advantageous point mutations

“Sumoylation plays a role in different cellular processes such as nuclear transport, programmed cell death or as an antiviral mechanism,” Friederike Berberich-Siebelt explains. Sumoylation defects have also been observed in various diseases such as cancer and herpesvirus infections.

In the study now published, the scientists worked with laboratory animals that had two actually insignificant point mutations in the NFATc1 gene which, however, prevent sumoylation. This is not necessarily a disadvantage: “The offspring of these animals is perfectly healthy. The modified NFATc1 even mediates specific signals that reduce the clinical symptoms of multiple sclerosis at least in the animal model,” Berberich-Siebelt explains. When using T cells that carry these mutations in stem cell transplantation, they are much less aggressive against the tissues of the host animals than “normal” cells.

Fascinating fundamental research

This effect is due to an increase in interleukin-2 at the beginning of the immune response at the biomolecular level. Interleukin-2 counteracts the differentiation into inflammatory T-cell subtypes and at the same time supports so-called regulatory T cells according to the authors of the study. It is quite possible that this discovery will have consequences for future stem cell transplantation which includes T-cell infusion. When using T cells in which NFATc1 is not sumoylated, this might prevent severe side effects, making the point mutation “a small modification with a big impact” according to Berberich-Siebelt.

To investigate this in more detail, Berberich-Siebelt and her team will continue to research the possibilities of therapeutic implementation within the framework of the Collaborative Research Center/Transregio “Control of graft-versus-host and graft-versus-leukaemia immune responses after allogeneic stem cell transplantation” funded by the German Research Foundation (DFG). “We want to find out whether CRISPR/Cas9 gene editing can be applied to human T cells to exhibit just the right amount of activity during hematopoietic stem cell transplantation,” the scientist says.

But the new findings are also relevant independently of these potential consequences for therapeutic applications. “We are basically interested in understanding the fine regulation in cells, such as the T-cell receptor signalling and the function of NFAT family members and their isoforms in this context,” says Berberich-Siebelt who finds the newly published results “fascinating.” After all, the scientists did not have to switch off a gene or activate it excessively as is often the case in research. Instead, two actually harmless point mutations and subtle direct effects were sufficient to ultimately flip the switch from inflammation, autoimmunity and rejection to tolerance. A small shift of the focus at the beginning of the immune response had been sufficient to accomplish this.

Story Source:

Materials provided by University of Würzburg. Original written by Gunnar Bartsch. Note: Content may be edited for style and length.

Source link

News

Exosome treatment improves recovery from heart attacks in a preclinical study — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

Science has long known that recovery from experimental heart attacks is improved by injection of a mixture of heart muscle cells, endothelial cells and smooth muscle cells, yet results have been limited by poor engraftment and retention, and researchers worry about potential tumorigenesis and heart arrhythmia.

Now research in pigs shows that using the exosomes naturally produced from that mixture of heart muscle cells, endothelial cells and smooth muscle cells — which were all derived from human induced pluripotent stem cells — yields regenerative benefits equivalent to the injected human induced pluripotent stem cell-cardiac cells, or hiPSC-CCs.

Exosomes are membrane-bound extracellular vesicles that contain biologically active proteins, RNAs and microRNAs. Exosomes are well known to participate in cell-to-cell communication, and they are actively studied as potential clinical therapies.

“The hiPSC-CC exosomes are acellular and, consequently, may enable physicians to exploit the cardioprotective and reparative properties of hiPSC-derived cells while avoiding the complexities associated with tumorigenic risks, cell storage, transportation and immune rejection,” said Ling Gao, Ph.D., and Jianyi “Jay” Zhang, M.D., Ph.D., University of Alabama at Birmingham corresponding authors of the study, published in Science Translational Medicine. “Thus, exosomes secreted by hiPSC-derived cardiac cells improved myocardial recovery without increasing the frequency of arrhythmogenic complications and may provide an acellular therapeutic option for myocardial injury.”

At UAB, Gao was a postdoctoral fellow in Biomedical Engineering, a joint department of the UAB School of Medicine and the UAB School of Engineering. Zhang is chair of the department.

Studies in large animals are necessary to identify, characterize and quantify responses to potential treatments. Prior to this current study, the feasibility of hiPSC-CC exosomes for cardiac therapy had been shown only in mouse models and in vitro work.

In the UAB experiments, juvenile pigs with experimental heart attacks had one of three treatments injected into the damaged myocardium: 1) a mixture of cardiomyocytes, endothelial cells and smooth muscle cells derived from human induced pluripotent stem cells, 2) exosomes extracted from the three cell types, or 3) homogenized fragments from the three cell types.

The researchers had two primary findings from the pig studies. First, they found that measurements of left-ventricle function, infarct size, wall stress, cardiac hypertrophy, apoptosis and angiogenesis in animals treated with hiPSC-CCs, hiPSC-CC fragments or hiPSC-CC exosomes were similar and significantly improved compared to animals that recovered without any of the three experimental treatments. Second, they found that exosome therapy did not increase the frequency of arrhythmia.

In experiments with cells or aortic rings grown in culture, they found that exosomes produced by hiPSC-CCs promoted blood vessel growth in cultured endothelial cells and isolated aortic rings. Furthermore, the exosomes protected cultured hiPSC-cardiomyocytes from the cytotoxic effects of serum-free low-oxygen media by reducing the programmed cell death called apoptosis and by maintaining intracellular calcium homeostasis, which has a direct beneficial effect on heart conductivity. The exosomes also increased cellular ATP content, which is beneficial since deficiencies in cellular ATP metabolism are believed to contribute to the progressive decline in heart function for patients with left ventricle hypertrophy and heart failure.

The researchers also found that some of these in vitro beneficial effects could also be mediated by synthetic mimics of the 15 most abundant microRNAs found in the hiPSC-CC exosomes. The researchers noted that knowledge of the potential role of microRNAs in clinical applications is still far from complete.

Story Source:

Materials provided by University of Alabama at Birmingham. Original written by Jeff Hansen. Note: Content may be edited for style and length.

Source link

News

UM171 saves another life — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

In a world first, a young man suffering from severe aplastic anemia who could not be helped by standard treatments has been given a life-saving blood transplant with the made-in-Canada UM171 molecule.

The procedure was done by a medical team at the Institute of Hemato-oncology and Cellular Therapy (iHOTC) of Maisonneuve-Rosemont Hospital and the Institute for Research in Immunology and Cancer, both affiliated with Université de Montréal.

The young man’s case history, including the lifesaving transplant, was recently published in the scientific journal European Journal of Haematology, highlighting the unique and revolutionary properties of the UM171 molecule.

An autoimmune disease, severe aplastic anemia destroys stem cells in bone marrow and leads to a halt in the production of red blood cells, white blood cells and platelets. For allografting (grafting between individuals) for this disease, the donor’s stem cells must be as compatible as possible with those of the recipient to avoid the risk of immunological complications.

No donor option

If no compatible family or unrelated donor can be found, stem cells from a semi-identical family donor, also known as a haplo-identical donor, may be considered, under certain conditions, as an alternative source of cells. However, a family member must be healthy and available for such a procedure; the young man in this case did not have that option.

Cord blood transplantation, which is less demanding in terms of compatibility, is a good option for many patients requiring a stem cell transplant. On the other hand, cord blood generally does not contain enough stem cells for an adult patient weighing more than 70 kg; it produces a slow rise in white blood cells with an increased risk of often fatal infections.

In addition, the rate of graft rejection — the destruction of infused cord cells by the recipient’s immune system — is very high in patients with severe aplastic anemia who have received multiple blood transfusions.

“It was after having exhausted all our treatment options that UM171, which had already proven itself in a clinical trial in blood cancer patients, came into play,” said UdeM medical professor Jean Roy, a hematologist and clinical researcher at the MRH. 35-fold increase

“As well as increasing the number of stem cells in a unit of umbilical cord blood by an average of 35 times, it greatly reduces the risk of a frequent long-term immunological complication (graft-versus-host disease) requiring years of use of toxic immunosuppressive drugs.”

The researchers’ success confirms the excellent performance of UM171, which has already been demonstrated in two other studies conducted by iHOTC research teams with very encouraging results. A third study is now underway.

“This young man’s story and the other studies with UM171 clearly demonstrate how innovative clinical research, set up by local investigators, can create a culture of excellence and improve care to save more lives,” said IHOTC director Denis Claude Roy.

“The future will certainly bring us more such accomplishments, and that’s very encouraging.”

Story Source:

Materials provided by University of Montreal. Note: Content may be edited for style and length.

Source link

News

Researchers demonstrate how changing the stem cell response to inflammation may reverse periodontal disease — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

Periodontal disease, also known as gum disease, is a serious infection that affects nearly 50 percent of Americans aged 30 years and older. If left unchecked, periodontal disease can destroy the jawbone and lead to tooth loss. The disease is also associated with higher risk of diabetes and cardiovascular disease.

The current treatment for periodontal disease involves opening the infected gum flaps and adding bone grafts to strengthen the teeth. But in new research published recently in the journal Frontiers in Immunology, Forsyth Institute scientists have discovered that a specific type of molecule may stimulate stem cells to regenerate, reversing the inflammation caused by periodontal disease. This finding could lead to the development of new therapeutics to treat a variety of systemic diseases that are characterized by inflammation in the body.

For the study, Dr. Alpdogan Kantarci, his PhD student Dr. Emmanuel Albuquerque, and their team removed stem cells from previously extracted wisdom teeth and placed the stem cells onto petri dishes. The researchers then created a simulated inflammatory periodontal disease environment in the petri dishes. Next, they added two specific types of synthetic molecules called Maresin-1 and Resolvin-E1, both specialized pro-resolving lipid mediators from omega-3 fatty acids. The scientists found that Mar1 and RvE1 stimulated the stem cells to regenerate even under the inflammatory conditions.

“Both Maresin-1 and Resolvin-1 reprogrammed the cellular phenotype of the human stem cells, showing that even in response to inflammation, it is possible to boost capacity of the stem cells so they can become regenerative,” said Dr. Kantarci, Associate Member of Staff at the Forsyth Institute.

This finding is important because it allows scientists to identify the specific protein pathways involved in inflammation. Those same protein pathways are consistent across many systemic diseases, including periodontal disease, diabetes, heart disease, dementia, and obesity.

“Now that we understand how these molecules stimulate the differentiation of stem cells in different tissues and reverse inflammation at a critical point in time, the mechanism we identified could one day be used for building complex organs” said Dr. Kantarci. “There is exciting potential for reprogramming stem cells to focus on building tissues.”

Story Source:

Materials provided by Forsyth Institute. Note: Content may be edited for style and length.

Source link

News

Survey finds American support for human-animal chimera research — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

In September 2015, the US National Institutes of Health placed a funding moratorium on research that involves introducing human pluripotent stem cells into animal embryos — a practice that experts say is vital for advancing the field of regenerative medicine. To assess attitudes on human-animal chimeric embryo research, investigators conducted a survey among 430 Americans. The results of the survey, which found that 82% of people are supportive of at least some parts of this research, appear October 1 in the journal Stem Cell Reports.

“The take-home point is that the overall support for this kind of research across the American public is strong,” says co-author Francis Shen, a professor of law at the University of Minnesota and executive director of the Harvard Massachusetts General Hospital Center for Law, Brain, and Behavior. “I think this speaks to the public’s interest in the transformative potential of regenerative medicine for addressing disease in a variety of organs.”

“Public attitudes were more supportive than I thought would have been possible in the current political climate,” says first author Andrew Crane, a researcher in the Department of Neurosurgery at the University of Minnesota.

Crane and senior author Walter Low, a professor in the Department of Neurosurgery and Stem Cell Institute at the University of Minnesota, conduct research on stem cell applications for neurological disorders like Parkinson’s disease. One project focuses on generating human neural stem cells within pig brains. After learning that colleagues in Japan had done a survey on public attitudes about this type of research, they decided to conduct a similar study in the United States. Low and Crane began a collaboration with the Japan group and with Shen, who specializes in ethics at the intersection of law and neuroscience.

The study included two waves of data collection: 227 participants were surveyed in July 2018 and 203 additional participants were surveyed in June 2020. The participants were recruited through an Amazon service called Mechanical Turk and were paid $1 for completing the survey. The questions in the survey were similar to those included in the Japanese study.

The participants knew “next to nothing “about this research going into the survey, Shen explains. “We used images, and we clarified how this research might be done, breaking it down into steps.”

The survey questions were designed to assess opinions on the progressive steps of human-animal chimeric embryo research, by asking participants which aspects of research they were willing to accept based on their personal feelings. For example, it included scenarios about first injecting human stem cells into a pig embryo, then transplanting that embryo into a pig uterus to produce a pig with a human organ, and finally transplanting that organ into a human patient. It also broke down research by organ, with support for some tissue types being higher than others: 61% for heart, 64% for blood, 73% for liver, and 62% for skin, versus 44% for sperm/eggs and 51% for brain.

“With regard to putting human brain cells into animal brains, we’ve heard concerns about the animals having some sort of human consciousness, but that’s quite far off from where the science is right now and from anything that we’ve tried to advocate for in our research,” Crane says. “We understand this is a concern that should not be taken lightly, but it shouldn’t prohibit us from moving the research forward.”

The survey was also designed to assess cultural differences, and the researchers were surprised to find that support was relatively high even among religious and cultural conservatives. The largest factor influencing opposition to the research was concern about animal rights.

“As investigators in the US, we’ve hit a roadblock with a lot of this research with regard to funding,” Crane says. He adds that a lack of funding could lead to the research moving to countries with fewer ethical safeguards in place.

“The three biggest concerns about this research are animal welfare, human dignity, and the possibility of neurological humanization,” Shen concludes. “We would love to do focus groups to look deeper at some of these questions.”

Story Source:

Materials provided by Cell Press. Note: Content may be edited for style and length.

Source link

News

Breakthrough for tomorrow’s dentistry — ScienceDaily

https://www.sciencedaily.com/images/scidaily-icon.png

New knowledge on the cellular makeup and growth of teeth can expedite developments in regenerative dentistry — a biological therapy for damaged teeth — as well as the treatment of tooth sensitivity. The study, which was conducted by researchers at Karolinska Institutet, is published in Nature Communications.

Teeth develop through a complex process in which soft tissue, with connective tissue, nerves and blood vessels, are bonded with three different types of hard tissue into a functional body part. As an explanatory model for this process, scientists often use the mouse incisor, which grows continuously and is renewed throughout the animal’s life.

Despite the fact that the mouse incisor has often been studied in a developmental context, many fundamental questions about the various tooth cells, stem cells and their differentiation and cellular dynamics remain to be answered.

Using a single-cell RNA sequencing method and genetic tracing, researchers at Karolinska Institutet, the Medical University of Vienna in Austria and Harvard University in the USA have now identified and characterised all cell populations in mouse teeth and in the young growing and adult human teeth.

“From stem cells to the completely differentiated adult cells we were able to decipher the differentiation pathways of odontoblasts, which give rise to dentine — the hard tissue closest to the pulp — and ameloblasts, which give rise to the enamel,” say the study’s last author Igor Adameyko at the Department of Physiology and Pharmacology, Karolinska Institutet, and co-author Kaj Fried at the Department of Neuroscience, Karolinska Institutet. “We also discovered new cell types and cell layers in teeth that can have a part to play in tooth sensitivity.”

Some of the finds can also explain certain complicated aspects of the immune system in teeth, and others shed new light on the formation of tooth enamel, the hardest tissue in our bodies.

“We hope and believe that our work can form the basis of new approaches to tomorrow’s dentistry. Specifically, it can expedite the fast expanding field of regenerative dentistry, a biological therapy for replacing damaged or lost tissue.”

The results have been made publicly accessible in the form of searchable interactive user-friendly atlases of mouse and human teeth. The researchers believe that they should prove a useful resource not only for dental biologists but also for researchers interested in development and regenerative biology in general.

Story Source:

Materials provided by Karolinska Institutet. Note: Content may be edited for style and length.

Source link

1 2
Privacy Settings
We use cookies to enhance your experience while using our website. If you are using our Services via a browser you can restrict, block or remove cookies through your web browser settings. We also use content and scripts from third parties that may use tracking technologies. You can selectively provide your consent below to allow such third party embeds. For complete information about the cookies we use, data we collect and how we process them, please check our Privacy Policy
Youtube
Consent to display content from Youtube
Vimeo
Consent to display content from Vimeo
Google Maps
Consent to display content from Google
Spotify
Consent to display content from Spotify
Sound Cloud
Consent to display content from Sound
Cart Overview