Category Archives: Stem Cells

This article was originally published here

Exp Mol Med. 2022 Apr 1. doi: 10.1038/s12276-022-00749-5. Online ahead of print.

ABSTRACT

Mesenchymal stem cells (MSCs) are a common kind of multipotent cell in vivo, but their heterogeneity limits their further applications. To identify MSC subpopulations and clarify their relationships, we performed cell mapping of bone-marrow-derived MSCs through single-cell RNA (scRNA) sequencing. In our study, three main subpopulations, namely, the stemness subpopulation, functional subpopulation, and proliferative subpopulation, were identified using marker genes and further bioinformatic analyses. Developmental trajectory analysis showed that the stemness subpopulation was the root and then became either the functional subpopulation or the proliferative subpopulation. The functional subpopulation showed stronger immunoregulatory and osteogenic differentiation abilities but lower proliferation and adipogenic differentiation. MSCs at different passages or isolated from different donors exhibited distinct cell mapping profiles, which accounted for their corresponding different functions. This study provides new insight into the biological features and clinical use of MSCs at the single-cell level, which may contribute to expanding their application in the clinic.

PMID:35365767 | DOI:10.1038/s12276-022-00749-5

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Single-cell RNA sequencing analysis of human bone-marrow-derived mesenchymal stem cells and functional subpopulation identification - DocWire News

I want to make sure that by 2025, we have a cost competitive product on the market [on parity with] organic [meat] and we feel very comfortable that we can get there, said Krijn de Nood, who was speaking to FoodNavigator-USA about the ongoing debate over the commercial viability of growing meat from animal cells, at scale, outside of an animal, a technology Impossible Foods founder Dr Pat Brown has dismissed as vaporware.

Asked about last years article in The Counter (drawing upon two techno-economic analyses of cell-cultured meat: CE Delft 2021 andHumbird 2020) arguing that cell-cultured meat faces "intractable technical challenges at food scale, de Nood said: Its always good to read those articles and test your hypotheses and see if you are wrong.

But if we look at our models, both on the scalability trajectory and on the cost reduction trajectory, we feel very comfortable that by 2025, we can go to the market with a price competitive product. The Delft analysis assumed 32 days for the whole process and we can do it - proliferating the cells and then [differentiating] them into muscle and fat cells in less than two weeks.

This also gives us a huge cost advantage from an energy and labor perspective.

While achieving certain cell densities is important, he said, What matters is the biomass accumulation rate. Maybe you can have great cell densities, but if it takes you six weeks to get to them, thats not so efficient, so its one of the reasons we chose iPScs [induced pluripotent stem cells], because they have a faster proliferation rate, they divide faster, so the accumulation of kilograms of meat is faster.

Obviously there's a risk accompanied with scaling up any process, but were not talking about a wild gamble here.

Meatable - which is working with porcine and bovine induced pluripotent stem cells - closed a $47m Series A round (bringing its total funding to $60m) last year, and has just hired former Chr. Hansen president and CEO Cees de Jong as chairman of the board; former Fonterra Europe & Africa president Hans Huistra as COO; and biochemist Jef Pinxteren as VP of development.

At our[pilot-scale]production facility in Delft, we have moved from grams to the kilograms range, so product development can take a big leap, plus for regulatory approval you also need to produce consistent batches, said de Nood.

We have gone from being an R&D company to being a food company.

For commercial launch, he said, Singapore[where cell-cultured meat products, from Eat Just, are already on sale, albeit on a tiny scale]is probably going to be an interesting entry market. After that, we hope that the US will open up for us, as from a market size perspective, its a much more attractive proposition than Singapore, although Singapore is a very good testing market as there are people with a lot of different ethnicities and a willingness to adopt new technologies.

Currently, Meatable is considering asemi-commercialfacility in Singapore, while a larger-scale facility capable of producing 10 kilotons a year would probably be better placed in a larger market such as the US or Europe.

In Europe, said de Nood,the positive thing is that the regulatory landscape is defined[firms must go through the Novel Food Regulation, a pre-market approval process],but it takes a long time, whereas in the US, the process is a work in progress [the FDA says it will publish draft guidance on the pre-market consultation process this year], but seems likely to move more rapidly, he said. "Hopefully months not years.

Meatables first commercial product will be pork, said de Nood. Pork is the most consumed meat globally, especially in Asia, plus there's also a supply demand imbalance right now because of swine fever. But we have also developed a beef line, which is super interesting, especially for Europe and the US our technology is species independent, so at some point we will dofish as well."

He added: Right now what we believe we need for commercial scale is about 10,000 liter bioreactors, but thats only at the beginning, and thats why its so special we have a collaboration with DSM, as they have experience of working with bioreactors on a large scale. DSM also has a lot of experience with taste and texture enhancers[that Meatable can tap into].

Asked about progress on enabling technologies for cell-cultured meat, de Nood said: If you just look at all the growth factors, the amino acids, the minerals that are required, what is very encouraging is that not only startups, but also big corporates are jumping into this, so we have a joint development agreement with DSM, which is really focused on reducing the cost of growth factors[produced via microbial fermentation].

There are several things we can do, so one is moving from pharma to food grade, one is finding other microorganisms to produce these growth factors, and there's also adaptation of the cells so they actually need less. There are a lot of opportunities to really get costs down quite significantly.

So what kinds of products is Meatable working on?

For the first products,said de Nood,we have the two [separate]production lines[for fat and muscle cells]and then we mix them at the end, but we are also working on whole cuts, which account for a huge percentage of the[conventional meat]market, and we are one of the few companies who can actually co-culture cells, so that's exciting stuff.

Asked about scaffolding, he said,We're using a variety of different scaffolds, but its a little bit IP sensitive.

Meatable is effectively reprogramming Hematopoietic stem cells (HSCs) so that they turn into [induced] pluripotent stem cells (iPS cells) or master cells that can differentiate into multiple cells types such as muscle and fat, and proliferate indefinitely.

Induced pluripotent stem cells behave like embryonic stem cells, but dont come from embryos, and dont require the slaughter or harm of any animal, CTO Dan Luining told us when the company emerged from stealth mode in 2018:"The collection method is truly non-invasive. After the calf is born and the umbilical cord is detached, we cannulate one of the veins in the cord and collect the blood in a blood bag. From this blood we isolate cells in the lab."

After that, the blood cells are effectively 'reprogrammed' to a pluripotent state using technologypioneered by Shinya Yamanakas lab in Kyoto, Japan that was awarded the2012 Nobel prize.

Luining added:"The method works by temporarily kickstarting the genes that were active during the state when the animal was only a few cells big. At that moment the cells were in a stage where they could become anything, which we call pluripotent. Professor Yamanaka figured out which genes were active at that time and showed that if you kickstart these genes again the cells behave like pluripotent cells.

"Once started the pluripotent state becomes stable and the cells self-perpetuate this state. These cells have amazing benefits including: unlimited proliferation, complete serum free growth, suspension growth, and pluripotency, the ability to become any cell type that we want.

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Meatable CEO weighs into debate over viability of cell-cultured meat: 'What matters is the biomass accumulation rate' - FoodNavigator-USA.com

Abstract: Treatment options for brain metastatic breast cancer is limited because the molecular mechanism for how breast cancer cells infiltrate the brain is not fully understood. In order for breast tumors to metastasize to the brain first cells need to detach from the primary tumor, enter in the blood circulation, survive within the microvascular niche, and then cross the blood brain barrier (BBB) to colonize into the brain. It is critical to understand how breast cancer cells transmigrate through the BBB to prevent brain metastasis. Nuclear respiratory factor 1 (NRF1) transcription factor has been reported to be highly active in several human cancers and its aberrant expression facilitates in the acquisition of breast cancer stem cells (BCSCs). Inhibitor of differentiation protein 3 (ID3), a transcription regulating protein, induces pluripotent endothelial stem cells (ESCs). Herein we investigated if NRF1-induced BCSCs could cross a BBB model and guiding of BCSCs by ID3-induced ESCs across the BBB. BCSCs and ESCs were subjected to functional gain/loss experiments to determine if NRF1/ID3 contributed to lineage specific BCSCs organ entry. First, we tested whether NRF1 promoted migration of breast cancer using a BBB model consisting of BCSCs or MDA-MB231 cells, brain endothelial cell layer, and astrocytes. NRF1 overexpression increased the propensity for BCSCs and NRF1-induced MDA-MB231 cells to adhere to brain endothelial cells and migrate across a human BBB model. Increased adhesion of NRF1 induced BCSCs to ESCsID3 was detected. NRF1 induced BCSCs crossed through the BBB model and this was promoted by ESCsID3. We also showed that environmental relevant exposure to PCBs (PCB153 and PCB77) produced differential effects. Treatment with PCB153 showed increased growth of NRF1 induced BCSCs tumor spheroids and increased in vivo migration of ESCsID3. Exosomal ID3 released from endothelial cells also supported the growth of NRF1 induced BCSCs and provide the basis for paracrine effects by ESCsID3 associated with breast tumors. Xenograft experiments showed that ID3 overexpressing brain ESCs not only supported the growth of BCSC tumorospheroids but guided them to the neural crest in zebrafish. These findings show for the first time a novel role for ID3 and NRF1 by which ESCsID3 help guide BCSCsNRF1 to distant metastatic sites where they most likely facilitate the colonization, survival, and proliferation of BCSCs. This knowledge is important for pre-clinical testing of NRF1/ID3 modifying agents to prevent the spread of breast cancer to the brain.

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Brain infiltration of breast cancer stem cells is facilitated by paracrine signaling by inhibitor of differentiation 3 to nuclear respiratory factor 1...

This article was originally published here

Stem Cell Res Ther. 2022 Mar 22;13(1):123. doi: 10.1186/s13287-022-02802-6.

ABSTRACT

BACKGROUND: Efficient mobilization of hematopoietic stem cells (HSCs) from bone marrow niche into circulation is the key to successful collection and transplantation in patients with hematological malignancies. The efficacy of various HSCs mobilization regimens has been widely investigated, but the results are inconsistent.

METHODS: We performed comprehensive databases searching for eligible randomized controlled trials (RCTs) that comparing the efficacy of HSCs mobilization regimens in patients with hematological malignancies. Bayesian network meta-analyses were performed with WinBUGS. Standard dose of granulocyte colony-stimulating factor (G-CSF SD) was chosen as the common comparator. Estimates of relative treatment effects for other regimens were reported as mean differences (MD) or odds ratio (OR) with associated 95% credibility interval (95% CrI). The surface under the cumulative ranking curve (SUCRA) were obtained to present rank probabilities of all included regimens.

RESULTS: Databases searching and study selection identified 44 eligible RCTs, of which the mobilization results are summarized. Then we compared the efficacy of mobilization regimens separately for patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) by including 13 eligible trials for network meta-analysis, involving 638 patients with MM and 592 patients with NHL. For patients with MM, data are pooled from 8 trials for 6 regimens, including G-CSF in standard dose (SD) or reduced dose (RD) combined with cyclophosphamide (CY), intermediate-dose cytarabine (ID-AraC) or plerixafor. The results show that compared with G-CSF SD alone, 3 regimens including ID-AraC + G-CSF SD (MD 14.29, 95% CrI 9.99-18.53; SUCRA 1.00), G-CSF SD + Plerixafor SD (MD 4.15, 95% CrI 2.92-5.39; SUCRA 0.80), and CY + G-CSF RD (MD 1.18, 95% CrI 0.29-2.07; SUCRA 0.60) are associated with significantly increased total number of collected CD34+ cells ( 106/kg), among which ID-AraC + G-CSF SD ranked first with a probability of being best regimen of 100%. Moreover, ID-AraC + G-CSF SD and G-CSF SD + Plerixafor SD are associated with significantly higher successful rate of achieving optimal target (collecting 4-6 106 CD34+ cells/kg). For patients with NHL, data are pooled from 5 trials for 4 regimens, the results show that compared with G-CSF SD alone, G-CSF SD + Plerixafor SD (MD 3.62, 95% CrI 2.86-4.38; SUCRA 0.81) and G-CSF SD plus the new CXC chemokine receptor-4 (CXCR-4) antagonist YF-H-2015005 (MD 3.43, 95% CrI 2.51-4.35; SUCRA 0.69) are associated with significantly higher number of total CD34+ cells collected. These 2 regimens are also associated with significantly higher successful rate of achieving optimal target. There are no significant differences in rate of achieving optimal target between G-CSF SD + Plerixafor SD and G-CSF + YF-H-2015005.

CONCLUSIONS: In conclusion, ID-AraC plus G-CSF is associated with the highest probability of being best mobilization regimen in patients with MM. For patients with NHL, G-CSF in combination with plerixafor or YF-H-2015005 showed similar improvements in HSCs mobilization efficacy. The relative effects of other chemotherapy-based mobilization regimens still require to be determined with further investigations.

PMID:35317856 | DOI:10.1186/s13287-022-02802-6

Original post:
Efficacy of hematopoietic stem cell mobilization regimens in patients with hematological malignancies: a systematic review and network meta-analysis...

Abstract: The evaluation of substances for their potency to induce embryotoxicity is controlled by safety regulations. Test guidelines for reproductive and developmental toxicity rely mainly on animal studies, which make up the majority of animal usage in regulatory toxicology. Therefore, there is an urgent need for alternative in vitro methods to follow the 3R principles. To improve human safety, cell models based on human cells are of great interest to overcome species differences. Here, human induced pluripotent stem cells (hiPSCs) are an ideal cell source as they largely recapitulate embryonic stem cells without bearing ethical concerns and they are able to differentiate into most cell types of the human body. Here, we set up and characterized a fetal bovine serum (FBS)-free hiPSC-based in vitro test method, called the human induced pluripotent stem cell test (hiPS Test), to evaluate the embryotoxic potential of substances. After 10 days in culture, hiPSCs develop into beating cardiomyocytes. As terminal endpoint evaluations, cell viability, qPCR analyses as well as beating frequency and area of beating cardiomyocytes by video analyses are measured. The embryotoxic positive and non-embryotoxic negative controls, 5-Fluorouracil (5-FU) and Penicillin G (PenG), respectively, were correctly assessed in the hiPS Test. More compounds need to be screened in the future for defining the assays applicability domain, which will inform us of the suitability of the hiPS Test for detecting adverse effects of substances on embryonic development.

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The Human Induced Pluripotent Stem Cell Test as an Alternative Method for Embryotoxicity Testing - Newswise

MELVILLE, N.Y., Jan. 04, 2022 (GLOBE NEWSWIRE) -- BioRestorative Therapies, Inc. (the Company" or BioRestorative) (NASDAQ:BRTX), a life sciences company focused on stem cell-based therapies, today announced that it has been awarded a Small Business Technology Transfer (STTR) Phase I grant for $256,000.The funds will be used specifically to evaluate the therapeutic effects on the Companys hypoxic cultured bone marrow derived mesenchymal stem cells (BRTX-100) after encapsulation with a PEG-peptide hydrogel. The work is being done in collaboration with Dr. Lori Setton, Chair of the Department of Biomedical Engineering at Washington University in St. Louis.

Dr. Setton developed the hydrogel from a PEG backbone conjugated with a proprietary formulation of peptides mimicking laminin and other matrix proteins selected for their ability to modulate cell phenotype and biosynthesis. The STTR aims to define the therapeutic potential and mechanism by which the newly synthesized hydrogel can optimally support the therapeutic delivery of hypoxic cultured bone marrow-derived stem cells.

The National Institutes of Health funds companies with the most innovative, cutting-edge ideas that have the potential to become commercial successes and make important societal impacts, said Lance Alstodt, CEO of BioRestorative Therapies.

We are tremendously grateful and honored to have been awarded this Phase I STTR. This collaboration is an important milestone that demonstrates our commitment to developing and expanding our product pipeline.

All proposals submitted to the NIH SBIR/STTR program undergo a rigorous merit-based review process. Once a small business is awarded a Phase I SBIR/STTR grant (up to $256,000), it becomes eligible to apply for a Phase II (up to $1,000,000). Small businesses with Phase II funding are eligible to receive up to $500,000 in additional matching funds with qualifying third-party investment or sales.

We are thrilled to collaborate with BioRestorative Therapies on this project. By receiving this grant, we will be able to evaluate the therapeutic benefits of our PEG-peptide hydrogel in combination with BioRestoratives hypoxic cultured stem cells, said Dr. Lori Setton, co-investigator on this project.

About BioRestorative Therapies, Inc.

BioRestorative Therapies, Inc. (www.biorestorative.com) develops therapeutic products using cell and tissue protocols, primarily involving adult stem cells. Our two core programs, as described below, relate to the treatment of disc/spine disease and metabolic disorders:

Disc/Spine Program (brtxDISC): Our lead cell therapy candidate,BRTX-100,is a product formulated from autologous (or a persons own) cultured mesenchymal stem cells collected from the patients bone marrow. We intend that the product will be used for the non-surgical treatment of painful lumbosacral disc disorders or as a complementary therapeutic to a surgical procedure. TheBRTX-100production process utilizes proprietary technology and involves collecting a patients bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. In an outpatient procedure,BRTX-100is to be injected by a physician into the patients damaged disc. The treatment is intended for patients whose pain has not been alleviated by non-invasive procedures and who potentially face the prospect of surgery. We have received authorization from the Food and Drug Administration to commence a Phase 2 clinical trial usingBRTX-100to treat chronic lower back pain arising from degenerative disc disease.

Metabolic Program (ThermoStem): We are developing a cell-based therapy candidate to target obesity and metabolic disorders using brown adipose (fat) derived stem cells to generate brown adipose tissue (BAT). BAT is intended to mimic naturally occurring brown adipose depots that regulate metabolic homeostasis in humans. Initial preclinical research indicates that increased amounts of brown fat in animals may be responsible for additional caloric burning as well as reduced glucose and lipid levels. Researchers have found that people with higher levels of brown fat may have a reduced risk for obesity and diabetes.

Forward-Looking Statements

This press release contains "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. You are cautioned that such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events or results to differ materially from those projected in the forward-looking statements as a result of various factors and other risks, including, without limitation, those set forth in the Company's latest Form 10-K filed with the Securities and Exchange Commission. You should consider these factors in evaluating the forward-looking statements included herein, and not place undue reliance on such statements. The forward-looking statements in this release are made as of the date hereof and the Company undertakes no obligation to update such statements.

CONTACT:

Email:ir@biorestorative.com

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BioRestorative Therapies Awarded an STTR Phase I Grant to - GlobeNewswire

When it comes to creating an effective and well-rounded approach to anti-aging skincare, its not likely that the foods youre eating ever come into consideration. However, ignoring your diet means youre missing out on a significant opportunity to bolster your complexion from the inside out, failing to make all the changes possible to preserve your appearance from the development of fine lines and wrinkles over time. Your skin is a reflection of your internal health and prioritizing certain foods can increase both collagen and stem cell production under the surface, effectively allowing you to look younger or age more gracefully in combination with the products youre using on the surface.

We checked in with board-certified dermatologist Dr. Anna Chacon to get the rundown on the best food to add into your diet in order to effectively boost stem cell production and smooth your skin, and with some small tweaks to your eating habits your skin will reflect these changes in no time.

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Not only are cruciferous vegetables great for promoting weight loss through their high fiber content, but these veggies are also known for improving your skin barrier and preserving your youthful appearance as well. According to Chacon, cauliflower, broccoli, kale and cabbage among other fibrous veggies can help to stimulate stem cell production, leading to a brighter complexion. These vegetables are full of these antioxidants and compounds which help to boost the enzymes in the liver that help to counteract harmful toxins we might digest or breathe then, Chacon explains. Within the skin, you might see more of a glow, and less breakouts for example such as acne flares.

Catering to your stem cells can help in the case of anti-aging much like increasing collagen within the body as these cells work to replace other cells which may have died. Making sure to eat a diet that boosts stem cells within your body can help to regenerate anything that has begun to deteriorate across your appearance, smoothing your complexion and keeping signs of aging at bay before they have even developed.

Stem cells are multipotent cells that are present in adult skin and can help when you differentiate into lineages of skin cells on the surface layers, explains Chacon. In layman's terms, stem cells can help to fill in cells that have begun to break down in your skins surface.

Its important to note that theres no cure-all solution to aging, and consuming cruciferous veggies daily wont necessarily turn back the clock on your appearance. However, integrating this group of foods into your diet will allow you to age more gracefully, delaying the appearance of deep wrinkles and fine lines that will naturally develop on your complexion with time. That being said, stem cells are often most useful for repairing damaged and wounded skin, but can also make an impact when it comes to anti-aging.

Some cells on the skin are active during cell renewal which can occur throughout life and also in wound healing of skin after an injury. The intake of vegetables that help to stimulate some self growth are more helpful when we are trying to heal from a major wound or injury, notes Chacon.

Vegetables will never be a bad idea to add to your diet, and with a number of benefits from their fiber content to the slew of other macro nutrients they provide, your body will thank you. Now, instead of merely focusing externally to improve your appearance, you can include your diet in the mix, utilizing cruciferous vegetables to boost stem cell production and allow for a smooth, ageless appearance for years to come. Or at the very least, improve the aging process.

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The One Food Derms Say You Should Be Eating Everyday For Stem Cell Production (AKA, To Look Years Younger) - SheFinds

Patients receiving hematopoietic stem cell transplantation appeared to have improved outcomes and a decreased incidence of acute graft-versus-host disease after being treated with itolizumab.

Treatment with itolizumab not only appeared to reduce host T cell response to donor grafts, but also appeared to decrease the incidence of acute graft-vs-host disease (aGVHD)post hematopoietic stem cell transplantation(HSCT) and improve patient outcomes, according to data presented at the 2021 American Society of Hematology Annual Meeting.1

Results indicated that itolizumab served to block the engagement between CD6, a costimulatory receptor primarily expressed on T cells, and activated leukocyte cell adhesion molecules. The agent was also found to induce the antigenic modulation of CD6 through a cleavage event. This event required membrane mobility of a serine protease, cell-to-cell contact with monocytes and natural killer (NK) cells, and functional binding of Fc receptors.

It is known that loss of CD6 on the cell surface leads to T cells that have reduced responses to T-cell receptormediated stimulation and alloreactivity. Alloreactive T cells are the primary driver of aGVHD, a serious toxicity associated with HSCT. In vitro, itolizumab produced T cells that were hyporesponsive and less alloreactive to stimulation by a mismatched unrelated donor. Furthermore, CD6-low cells responded less to stimulation vs CD6-high cells in the absence of antibody treatment, which suggests that the loss of surface CD6 is enough to generate cells that are hyporesponsive to stimulation under inflammatory conditions.

This further validates the potential for CD6 to be a therapeutic target for treating aGVHD and for itolizumab to be an effective treatment for alleviating disease pathology, presenting study author Dalena Chu, MS, of Equillium, Inc. wrote in the poster presentation.

CD6 is known to engage with ALCAM to encourage synapse formation, T-cell activation, and migration to tissues. Data from prior studies have shown that CD6 is expressed on reconstituting T cells soon after HSCT, and the ex vivo depletion of CD6-positive donor cells prior to transplant decreases the incidence of aGVHD.2

Itolizumab, a humanized anti-CD6 monoclonal antibody, blocks engagement between CD6 and ALCAM to reduce T-cell stimulation. The goal of the current study shared at the meeting was to further characterize the mechanism of CD6 loss with the utilization of itolizumab and understand the functional outcomes of the loss of CD6.

Additional findings showed that monocytes were required for CD6 cleavage induced by itolizumab. Investigators isolated T cells, monocytes, NK cells, and B cells from PBMCs and then treated the T cells with either itolizumab or the isotype in the presence of monocytes, NK cells, or B cells. CD6 loss was observed on T cells only when monocytes were present, although loss was detected to a lesser extent when NK cells were present.

Investigators also treated T cells with either itolizumab or the isotype in the presence of an increasing amount of monocytes. CD6 modulation that was induced by itolizumab was noted on enriched T cells that had increasing numbers of monocytes and increasing numbers of monocytes was noted to be associated with a greater loss of CD6.

Moreover, cell-to-cell contract was required to induce CD6 cleavage with itolizumab. After T cells and monocytes were enriched from PBMCs using magnetic negative selection, they were then plated in a 0.4-m transwell chamber. Subsequently, cells from the lower chamber were evaluated using flow cytometry to measure surface levels of CD6 on T cells. Results indicated that loss was only observed when T cells and monocytes physically encountered each other.

PBMCs were also pretreated with Fc receptorblocking antibodies for 30 minutes before itolizumab. Results showed that blocking CD64 or FcyRI resulted in a significant reduction of CD6 cleavage, suggesting that the functional binding of itolizumab to FcyRI preceded CD6 cleavage. Additionally, investigators found that by taking N-glycans out of the antibody, the ability for Fc-binding was reduced. Moreover, although the deglycosylated variant of itolizumab was found to induce CD6 loss on surface cells when administered at the same concentration as itolizumab, it was found to have less efficacy.

Additionally, itolizumab was found to reduce the proliferation of CD4-positive responder cells. Specifically, it increased the frequency of nave CD4-positive cells by approximately 50% and decreased the frequency of effector memory CD4-positive cells by approximately 18.6%. Treatment with the agent also reduced the level of activation and proliferation of responder cells.

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aGVHD Incidence Following HSCT May be Reduced Following Treatment With Itolizumab - Cancer Network

NORWICH, United Kingdom Dont be in a rush to lose that extra fat from the holidays, it might actually help you fight infections. Thats the conclusion of a new study that discovered another way of boosting the bodys immune system: fatty acids. As the main component of fat, researchers from the University of East Anglia say fatty acids provide the immune system with energy to fight harmful bacteria, like Salmonella.

Due to the overuse of antibiotics, bacteria are becoming increasingly drug-resistant over time. The World Health Organization (WHO) warns that antibiotic resistance is one of the biggest threats to global health, food security, and development today.

The bodys fat stores aid in the fight against antibiotic-resistant pathogens by supplying enough energy to produce millions of bacteria-killing white blood cells, the scientists say. The discovery could help develop new treatments for diseases caused by bacteria like Salmonella and Methicillin-resistant Staphylococcus aureus (MRSA).

Our results provide insight into how the blood and immune system is able to respond to infection. Fighting infection takes a lot of energy and fat stores are huge energy deposits, which provide the fuel for the blood stem cells to power up the immune response. Working out the mechanism through which this fuel boost works gives us new ideas on how to strengthen the bodys fight against infection in the future, says study author Dr. Stuart Rushworth in a university release.

Salmonella is a bacterial infection that causes diarrhea, vomiting, abdominal pain, fever, and sepsis. People usually encounter it when eating food contaminated by animal feces. In the U.S., Salmonella causes about 1.35 million infections and 420 deaths every year.

The researchers examined how the bodys immune system responds to the Salmonella bacteria. By analyzing liver damage, they were able to witness how blood stem cells in bone marrow respond to the infection. Fat stores entered into the bloodstream, effectively feeding the stem cells to make millions of Salmonella-fighting white blood cells.

The team also mapped out the transfer of these fatty acids, adding that their findings could help develop new treatments for liver infections.

Our results allow us to understand how our immune system uses fat to fuel the response to infection. Defining these mechanisms will enable us to develop new therapeutics to treat infections in the liver, says study co-author Dr. Naiara Beraza at the Quadram Institute in Norwich, England.

New treatments to infections like Salmonella are desperately needed as these diseases are becoming increasingly resistant to antibiotics.

In the future, I hope our findings will help improve treatment for vulnerable and older people with infections, by strengthening their immune response. With antibiotic resistance being such a present and widespread challenge for society, there is an urgent need to explore novel ways like this to help the bodys immune system to fight infection, Dr. Rushworth concludes.

The findings are published in the journal Nature Communications.

South West News Service writer Tom Campbell contributed to this report.

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Fat cells give the body energy to combat infections - Study Finds

PHILADELPHIA, Jan. 04, 2022 (GLOBE NEWSWIRE) -- Century Therapeutics (NASDAQ: IPSC), an innovative biotechnology company developing induced pluripotent stem cell (iPSC)-derived cell therapies in immuno-oncology, today announced that Lalo Flores, Ph.D., Chief Executive Officer, will present virtually at the 40th Annual J.P. Morgan Healthcare Conference on Tuesday, January 11, 2022 at 1:30 PM ET.

A live webcast of the event will be available on the Events & Presentations page in the Investors section of the Companys website at https://investors.centurytx.com/events-and-presentations. A replay of the webcast will be archived on the Companys website for 30 days following the presentation.

About Century Therapeutics

Century Therapeutics, Inc. (NASDAQ: IPSC) is harnessing the power of adult stem cells to develop curative cell therapy products for cancer that we believe will allow us to overcome the limitations of first-generation cell therapies. Our genetically engineered, iPSC-derived iNK and iT cell product candidates are designed to specifically target hematologic and solid tumor cancers. We are leveraging our expertise in cellular reprogramming, genetic engineering, and manufacturing to develop therapies with the potential to overcome many of the challenges inherent to cell therapy and provide a significant advantage over existing cell therapy technologies. We believe our commitment to developing off-the-shelf cell therapies will expand patient access and provide an unparalleled opportunity to advance the course of cancer care. For more information on Century Therapeutics please visitwww.centurytx.com.

Century Therapeutics Forward-Looking Statement

This press release contains forward-looking statements within the meaning of, and made pursuant to the safe harbor provisions of, The Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by terms such as may, might, will, should, expect, plan, aim, seek, anticipate, could, intend, target, project, contemplate, believe, estimate, predict, forecast, potential or continue or the negative of these terms or other similar expressions. These statements are not guarantees of future performance These risks and uncertainties are described more fully in the Risk Factors section of our most recent filings with the Securities and Exchange Commission and available at http://www.sec.gov. You should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

For More Information: Company: Elizabeth Krutoholow investor.relations@centurytx.comInvestors: Melissa Forst/Maghan Meyers century@argotpartners.comMedia: Joshua R. Mansbach century@argotpartners.com

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Century Therapeutics to Present at the 40th Annual JP Morgan Healthcare Conference - GlobeNewswire