AGOURA HILLS, Calif., Aug. 17, 2022 (GLOBE NEWSWIRE) -- Oncotelic Therapeutics, Inc. (“Oncotelic” or the “Company”) (OTCQB:OTLC), developer of treatments for rare and orphan indications, including Parkinson Disease and various cancers, today announced that the Company will be participating at Biotechgate Digital Partnering – a business development & licensing event - Aug 29 - Sep 2, 2022. An updated investor slide deck will be available at our website after the event.

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Oncotelic Participating at Biotechgate Digital Partnering

PALO ALTO, Calif., Aug. 17, 2022 (GLOBE NEWSWIRE) -- Scilex Holding Company (“Scilex”), a commercial biopharmaceutical company focused on developing and commercializing non-opioid therapies for patients with acute and chronic pain, today announced the signing of a Product Distribution Agreement (“Agreement”) for certain designated territories with CH Trading Group LLC (“CH Trading”), an international import, export and trading company focused on the Middle East and North Africa (MENA) Region and other markets, to distribute Scilex’s lead non-opioid commercial pain management product, ZTlido®. Scilex is a nearly 100% (or over 99.9%) majority-owned subsidiary of Sorrento Therapeutics, Inc. (Nasdaq: SRNE, “Sorrento”).

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Scilex Holding Company, a Sorrento Company, Announces Exclusive Product Distribution Agreement with CH Trading Group LLC to Expand Commercialization...

CARLSBAD, Calif., Aug. 17, 2022 (GLOBE NEWSWIRE) -- Palisade Bio, Inc. (Nasdaq: PALI), a clinical stage biopharmaceutical company advancing therapies for acute and chronic gastrointestinal (GI) complications, today announced the first patient has been dosed in its Phase 3 study evaluating LB1148 to accelerate the return of bowel function in adult patients undergoing gastrointestinal surgery.

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Palisade Bio Announces First Patient Enrolled and Dosed in Pivotal Phase 3 Study Evaluating LB1148 for Postoperative Return of Bowel Function

CINCINNATI, Aug. 17, 2022 (GLOBE NEWSWIRE) -- Blue Water Vaccines Inc. (“BWV” or “Blue Water Vaccines” or “the Company”), a biopharmaceutical company developing transformational vaccines to address significant global health challenges, today announced that the Company plans to explore the potential to develop a novel monkeypox vaccine using its norovirus shell and protrusion (S&P) virus-like particle (VLP) platform.

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Blue Water Vaccines Announces Exploration of Its Virus-Like Particle (VLP) Platform for Use in Monkeypox Vaccine Candidate

LOS ANGELES, Aug. 17, 2022 (GLOBE NEWSWIRE) -- Trethera Corporation (“Trethera”), a clinical stage biopharmaceutical company committed to developing novel drugs targeting nucleotide metabolism for the treatment of cancer and autoimmune diseases, announces today that the United States Patent and Trademark Office (USPTO) issued a Notice of Allowance for a composition of matter patent covering the polymorphic form of TRE-515. The resulting US patent will extend the patent protection for TRE-515 in the United States by seven years through November 2041. TRE-515 is a first-in-class drug targeting the enzyme deoxycytidine kinase (dCK) and currently in Phase 1 clinical trials.

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Trethera Receives U.S. Patent Office Notice of Allowance Covering TRE-515 Structural Claims, Extending Protections to Late 2041

CAMBRIDGE, Mass., Aug. 17, 2022 (GLOBE NEWSWIRE) -- Alphageneron Pharmaceuticals, Inc. (“Alphageneron” or the “Company”), a clinical stage pharmaceutical company developing a diverse platform of cell and antibody-based therapeutic candidates to treat cancer, announced today that their Chief Executive Officer, Robert K. Brooks, JD, will participate in the Cell Therapy Durability Response Summit that will be held August 22-23, 2022.

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Alphageneron to Participate in Cell Therapy Durability Response Summit

VANCOUVER, British Columbia, Aug. 17, 2022 (GLOBE NEWSWIRE) -- Segra International Corp. (“Segra”), an agriculture technology company is pleased to announce the publishing of a landmark white paper addressing the recent widespread identification of mitoviruses in cannabis cultivars.

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Cannabis Mitoviruses: An Introduction and State of Knowledge

BRISBANE, Calif., Aug. 17, 2022 (GLOBE NEWSWIRE) -- Annexon, Inc. (Nasdaq: ANNX), a clinical-stage biopharmaceutical company developing a new class of complement medicines for patients with classical complement-mediated autoimmune, neurodegenerative and ophthalmic disorders, today announced that it has granted equity inducement awards to three new non-executive employees under the terms of the 2022 Employment Inducement Award Plan. The equity awards were approved on August 16, 2022, in accordance with Nasdaq Listing Rule 5635(c)(4).

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Annexon Reports Inducement Grants to New Employees Under Nasdaq Listing Rule 5635(c)(4)

Ad hoc announcement pursuant to Art. 53 LR of the SIX Swiss Exchange

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ObsEva Files Second Quarter 2022 Financial Statements

Funding from the Cancer Prevention and Research Institute of Texas (CPRIT), the second largest global public funder of cancer research, will support the majority of the development costs of 186RNL for leptomeningeal metastases.

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Plus Therapeutics Awarded $17.6 Million from State of Texas

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Avicanna Announces Closing of Strategic Private Placement

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Bone Therapeutics to broaden and derisk therapeutic portfolio by acquiring majority participation in Medsenic

Research led by Muhammad Riaz, PhD, Jinkyu Park, PhD, and Lorenzo Sewanan, MD, PhD, from the Qyang and Campbell laboratories at Yale, provides a mechanism to identify abnormalities linked with a hereditary cardiac condition, hypertrophic cardiomyopathy (HCM), in which walls of the left ventricle become abnormally thick and often stiff. The findings appear in the journal Circulation.

Patients with familial HCM have an increased risk of sudden death, heart failure, and arrhythmias. HCM is the most common inherited cardiac disease, affecting one in 500 people. The disease is thought to be caused by mutations that regulate cardiac muscle contraction, compromising the hearts ability to pump blood. However, the mechanisms behind the disease are poorly understood.

For this multi-model study, the researchers used stem cell approaches to understand the mechanisms that drive inherited HCM. The technology, induced pluripotent stem cells (iPSCs), can accelerate insights into the genetic causes of disease and the development of new treatments using the patients own cells.

This is a humbling experience that a patients disease phenotypes teach researchers fundamental basic knowledge that sets the stage for innovative new therapies. Furthermore, our research has established a great model to assist many physicians at Yale School of Medicine and Yale New Haven Hospital to unravel mechanistic insights into disease progression using the patients own iPSCs and engineered tissues, said Yibing Qyang, PhD, associate professor of medicine (cardiology) and of pathology.

We wanted to understand the disease mechanism and find a new therapeutic strategy, Park said.

Probing the heart disorders mechanismThe concept originated with an 18-month-old patient who suffered from familial HCM. Through a collaboration with Daniel Jacoby, MD, adjunct associate professor of cardiovascular medicine and an expert on HCM, who provided medical care for this patient, Park and the team used stem cell technologies to address a fundamental question, the disease mechanisms behind HCM. They collected 10 cc of the patients blood and introduced stem cell factors into the blood cells to generate self-renewable iPSCs. By applying cardiac knowledge, they coaxed iPSCs into patients own cardiomyocytes (heart cells) for cardiac disease studies. We discovered a general mechanism which explains the disease progression, said Park.

Next, they engineered heart tissues that resembled the early-onset disease scenario of the young patient. The disease was a severe presentation at the age of 18 months, which suggested that the disease started at the fetal/neonatal stage.

The next phase of the study was to recreate a 3-D model that was used to mimic the progression of the disease, including mechanical properties such as contraction and force production of that muscle, to understand how much force is compromised if the mutation is present. This was performed in collaboration with Stuart Campbell, PhD, and Sewanan from Yales Department of Biomedical Engineering. Coupled with computational modeling for muscle contraction, the authors developed robust systems that allowed them to examine the biomechanical properties of the tissue at three-dimensional levels.

Finally, using advanced gene editing technologies, the research team modified these mutations. They discovered that after the mutations were corrected, the disease was reversed. These insights about sarcomeric protein mutations could lead to novel therapeutics for HCM and other diseases. The interaction between mutations could also suggest that the same biomechanical mechanism exists in other conditions such as ischemic heart disease.

Our research has established a great model to assist many physicians at Yale School of Medicine and Yale New Haven Hospital to unravel mechanistic insights into disease progression using the patients own iPSCs and engineered tissues.

Yibing Qyang, PhDWe can apply these findings to cardiac conditions associated with hypertension, diabetes, or aging, said Riaz.

Applying the findings to heart diseaseOne of the fundamental challenges was that we needed to generate iPSCs from the patients family, Riaz added. Using this technology, Park was able to recreate primary cells from the cells of a patient with HCM, a process which takes over a month. Riaz and Park used stem cells to identify the vital role of pathological tissue remodeling, which is caused by sarcomeric hypertrophic cardiomyopathy mutations.

We are hopeful that our findings will be replicated in the scientific community, said Riaz. This is an example of bed to bench research, where scientists extract materials from clinics and conduct the experiment in the laboratory and then discover new methods to treat patients.

The authors also noted that RNA sequencing could be used as a guide to characterize the disease at a molecular level. Scientists may be able to identify more targeted drugs by examining the biomechanical properties of the tissue. We can now screen multiple drugs to see whether any of those drugs are able to rescue the phenotype, they said.

Riaz, now an associate research scientist in the Qyang lab, began as a cancer researcher. He earned a PhD from the Erasmus University Medical Center, based in Rotterdam, Netherlands. He later studied genetic disorders in skeletal muscle disease before joining the lab in 2017.

Park, also from the Qyang lab, graduated from Seoul National University, South Korea in 2013. He completed postdoctoral research at the University of Missouri where he focused on vascular biology and emerging areas in stem cell technology.

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Yale University: Uncovering New Approaches to a Common Inherited Heart Disorder | India Education - India Education Diary

Collaboration NCDRF. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017;390:262742.

Article Google Scholar

Hales CM, Fryar CD, Carroll MD, Freedman DS, Ogden CL. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA. 2018;319:17235.

PubMed PubMed Central Article Google Scholar

Kenchaiah S, Evans JC, Levy D, Wilson PW, Benjamin EJ, Larson MG, et al. Obesity and the risk of heart failure. N Engl J Med. 2002;347:30513.

PubMed Article Google Scholar

Aune D, Sen A, Norat T, Janszky I, Romundstad P, Tonstad S, et al. Body mass index, abdominal fatness, and heart failure incidence and mortality: a systematic review and dose-response meta-analysis of prospective studies. Circulation. 2016;133:63949.

PubMed Article Google Scholar

DeMaria EJ. Bariatric surgery for morbid obesity. N Engl J Med. 2007;356:217683.

CAS PubMed Article Google Scholar

Sjostrom L. Review of the key results from the Swedish Obese Subjects (SOS) trial - a prospective controlled intervention study of bariatric surgery. J Intern Med. 2013;273:21934.

CAS PubMed Article Google Scholar

Jacobs L, Efremov L, Ferreira JP, Thijs L, Yang WY, Zhang ZY, et al. Risk for Incident Heart Failure: A Subject-Level Meta-Analysis From the Heart OMics in AGEing (HOMAGE) Study. J Am Heart Assoc. 2017;6.

Sahle BW, Owen AJ, Chin KL, Reid CM. Risk prediction models for incident heart failure: a systematic review of methodology and model performance. J Card Fail. 2017;23:6807.

PubMed Article Google Scholar

Tyers M, Mann M. From genomics to proteomics. Nature. 2003;422:1937.

CAS PubMed Article Google Scholar

Singla P, Bardoloi A, Parkash AA. Metabolic effects of obesity: a review. World J Diabetes. 2010;1:7688.

PubMed PubMed Central Article Google Scholar

Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898918.

PubMed Article Google Scholar

Sjostrom L, Larsson B, Backman L, Bengtsson C, Bouchard C, Dahlgren S, et al. Swedish Obese Subjects (SOS). Recruitement for an interventional study and a selected description of the obese state. Int J Obesity. 1992;16:46579.

CAS Google Scholar

Essebag V, Genest J Jr., Suissa S, Pilote L. The nested case-control study in cardiology. Am Heart J. 2003;146:58190.

PubMed Article Google Scholar

Hsieh FY, Bloch DA, Larsen MD. A simple method of sample size calculation for linear and logistic regression. Stat Med. 1998;17:162334.

CAS PubMed Article Google Scholar

Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc. 1995;57:289300.

Google Scholar

Kamburov A, Stelzl U, Lehrach H, Herwig R. The ConsensusPathDB interaction database: 2013 update. Nucleic Acids Res. 2013;41:D793800.

CAS PubMed Article Google Scholar

Greenland S. Tests for interaction in epidemiologic studies: a review and a study of power. Stat Med. 1983;2:24351.

CAS PubMed Article Google Scholar

Brookes ST, Whitely E, Egger M, Smith GD, Mulheran PA, Peters TJ. Subgroup analyses in randomized trials: risks of subgroup-specific analyses; power and sample size for the interaction test. J Clin Epidemiol. 2004;57:22936.

PubMed Article Google Scholar

Schwenk RW, Vogel H, Schurmann A. Genetic and epigenetic control of metabolic health. Mol Metab. 2013;2:33747.

CAS PubMed PubMed Central Article Google Scholar

Xu S, Lind L, Zhao L, Lindahl B, Venge P. Plasma prolylcarboxypeptidase (angiotensinase C) is increased in obesity and diabetes mellitus and related to cardiovascular dysfunction. Clin Chem. 2012;58:11105.

CAS PubMed Article Google Scholar

Micheau O Regulation of TNF-related apoptosis-inducing ligand signaling by glycosylation. Int J Mol Sci. 2018;19.

Hanasaki K, Varki A, Stamenkovic I, Bevilacqua MP. Cytokine-induced beta-galactoside alpha-2,6-sialyltransferase in human endothelial cells mediates alpha 2,6-sialylation of adhesion molecules and CD22 ligands. J Biol Chem. 1994;269:1063743.

CAS PubMed Article Google Scholar

Kosmala W, Plaksej R, Przewlocka-Kosmala M, Kuliczkowska-Plaksej J, Bednarek-Tupikowska G, Mazurek W. Matrix metalloproteinases 2 and 9 and their tissue inhibitors 1 and 2 in premenopausal obese women: relationship to cardiac function. Int J Obes. 2008;32:76371.

CAS Article Google Scholar

Cynis H, Hoffmann T, Friedrich D, Kehlen A, Gans K, Kleinschmidt M, et al. The isoenzyme of glutaminyl cyclase is an important regulator of monocyte infiltration under inflammatory conditions. EMBO Mol Med. 2011;3:54558.

CAS PubMed PubMed Central Article Google Scholar

Zhu R, Liu C, Tang H, Zeng Q, Wang X, Zhu Z, et al. Serum Galectin-9 levels are associated with coronary artery disease in chinese individuals. Mediators Inflamm. 2015;2015:457167.

PubMed PubMed Central Google Scholar

Suzuki K. The multi-functional serpin, protein C inhibitor: beyond thrombosis and hemostasis. J Thromb Haemost. 2008;6:201726.

CAS PubMed Article Google Scholar

Ruge T, Carlsson AC, Ingelsson E, Riserus U, Sundstrom J, Larsson A, et al. Circulating endostatin and the incidence of heart failure. Scand Cardiovasc J. 2018;52:2449.

CAS PubMed Article Google Scholar

Stenemo M, Nowak C, Byberg L, Sundstrom J, Giedraitis V, Lind L, et al. Circulating proteins as predictors of incident heart failure in the elderly. Eur J Heart Fail. 2018;20:5562.

CAS PubMed Article Google Scholar

Rip J, Nierman MC, Ross CJ, Jukema JW, Hayden MR, Kastelein JJ, et al. Lipoprotein lipase S447X: a naturally occurring gain-of-function mutation. Arterioscler Thromb Vasc Biol. 2006;26:123645.

CAS PubMed Article Google Scholar

Bjorkbacka H, Yao Mattisson I, Wigren M, Melander O, Fredrikson GN, Bengtsson E, et al. Plasma stem cell factor levels are associated with risk of cardiovascular disease and death. J Intern Med. 2017;282:50821.

CAS PubMed Article Google Scholar

Yang H, Geiger M. Cell penetrating SERPINA5 (ProteinC inhibitor, PCI): More questions than answers. Semin Cell Dev Biol. 2017;62:18793.

CAS PubMed Article Google Scholar

Carroll VA, Griffiths MR, Geiger M, Merlo C, Furlan M, Lammle B, et al. Plasma protein C inhibitor is elevated in survivors of myocardial infarction. Arterioscler Thromb Vasc Biol. 1997;17:1148.

CAS PubMed Article Google Scholar

Wang XQ, Liu ZH, Xue L, Lu L, Gao J, Shen Y, et al. C1q/TNF-related protein 1 links macrophage lipid metabolism to inflammation and atherosclerosis. Atherosclerosis. 2016;250:3845.

CAS PubMed Article Google Scholar

Wang H, Wang R, Du D, Li F, Li Y. Serum levels of C1q/TNF-related protein-1 (CTRP-1) are closely associated with coronary artery disease. BMC Cardiovasc Disord. 2016;16:92.

PubMed PubMed Central Article CAS Google Scholar

Kharitonenkov A, Shiyanova TL, Koester A, Ford AM, Micanovic R, Galbreath EJ, et al. FGF-21 as a novel metabolic regulator. J Clin Invest. 2005;115:162735.

CAS PubMed PubMed Central Article Google Scholar

Fisher FM, Chui PC, Antonellis PJ, Bina HA, Kharitonenkov A, Flier JS, et al. Obesity is a fibroblast growth factor 21 (FGF21)-resistant state. Diabetes. 2010;59:27819.

CAS PubMed PubMed Central Article Google Scholar

Dupont M, Wu Y, Hazen SL, Tang WH. Cystatin C identifies patients with stable chronic heart failure at increased risk for adverse cardiovascular events. Circ Heart Fail. 2012;5:6029.

CAS PubMed PubMed Central Article Google Scholar

Shulman A, Peltonen M, Sjostrom CD, Andersson-Assarsson JC, Taube M, Sjoholm K, et al. Incidence of end-stage renal disease following bariatric surgery in the Swedish Obese Subjects Study. Int J Obes (Lond). 2018;42:96473.

CAS Article Google Scholar

Rothberg AE, McEwen LN, Herman WH. Severe obesity and the impact of medical weight loss on estimated glomerular filtration rate. PLoS One. 2020;15:e0228984.

CAS PubMed PubMed Central Article Google Scholar

Levey AS, Schoolwerth AC, Burrows NR, Williams DE, Stith KR, McClellan W, et al. Comprehensive public health strategies for preventing the development, progression, and complications of CKD: report of an expert panel convened by the Centers for Disease Control and Prevention. Am J Kidney Dis. 2009;53:52235.

PubMed Article Google Scholar

Zannad F, Ferreira JP, Pocock SJ, Zeller C, Anker SD, Butler J, et al. Cardiac and kidney benefits of empagliflozin in heart failure across the spectrum of kidney function: insights from EMPEROR-Reduced. Circulation. 2021;143:31021.

CAS PubMed Article Google Scholar

Ingelsson E, Arnlov J, Sundstrom J, Lind L. The validity of a diagnosis of heart failure in a hospital discharge register. Eur J Heart Fail. 2005;7:78791.

PubMed Article Google Scholar

The cause of death register 2018 [Available from: http://www.socialstyrelsen.se/statistics/statisticaldatabase/help/causeofdeath%5D.

Assarsson E, Lundberg M, Holmquist G, Bjorkesten J, Thorsen SB, Ekman D, et al. Homogenous 96-plex PEA immunoassay exhibiting high sensitivity, specificity, and excellent scalability. PLoS One. 2014;9:e95192.

PubMed PubMed Central Article CAS Google Scholar

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Heart failure in obesity: insights from proteomics in patients treated with or without weight-loss surgery | International Journal of Obesity -...

Immediate cord clamping (ICC), within a few seconds after birth, became routine in the latter half of the 20th century, as part of a tranche of medical birth-related interventions that collectively, undoubtedly improved maternal and neonatal survival and outcomes [1]. The trend to ICC (within 15-20 seconds after birth) was partly driven by some early studies suggesting that the most benefit in terms of blood volume is achieved within this time frame [2], and that deferred cord clamping (DCC) increased rates of polycythemia and jaundice [1]. It may also have been partly driven by increased rates of operative deliveries and consequent pressure to minimize surgical times, as well as the increased availability and effectiveness of neonatal resuscitation. Furthermore, ICC was proposed as a means to reduce the risk of maternal exposure to fetal blood group antigens at a time (before RhD immunoprophylaxis) when hemolytic disease of the fetus and newborn was far more common than it is now.

Formal evidence that ICC was beneficial was never sought, and recent research summarized in systematic reviews [3-6] has suggested that it may be harmful when compared with DCC for various intervals from 30 seconds until when the cord stops pulsating (defined in some studies as physiological cord clamping). ICC before the onset of breathing exposes the newborn baby to a period of significantly restricted cardiac function, whereas DCC until after the onset of breathing (which often does not occur until late in the first minute after birth) may mean that the expanding pulmonary circulation is able to fill with blood from the placenta, rather than by reverse flow across the ductus arteriosus [7]. This may improve left ventricular preload and stabilize pressures and flows in major vessels [7].

In addition, when cord clamping is deferred, babies may receive a transfusion of blood from the umbilical cord and placenta. A recent systematic review demonstrated that DCC in preterm babies improves peak hematocrit in the first week by 2.7% (95% confidence intervals (CI) 1.88-3.52) and reduced the proportion of babies receiving any subsequent blood transfusion (RD: -0.07, 95%CI -0.11 to -0.04) [6]. Some studies have found a weight increase in the first two minutes after birth when the cord is not clamped, supporting the hypothesis of placental transfusion [8]. Yet, recent evidence shows that placental transfusion may not always occur (Conference abstract: Vijayaselvi R, Abraham A, Kumar M, Kuruvilla A, Mathews J, Duley L. Measuring Umbilical Flow and Placental Transfusion for Preterm Births: Weighing Babies at 33-36 Weeks Gestation with Cord Intact. 1st Congress of Joint European Neonatal Societies; 2015).

The relative roles of cardiovascular stabilization at birth versus placental transfusion in improving outcomes have not been established. Understanding the contributions of these two mechanisms has significant implications for research and practice: for example, if the size of placental transfusion is more important, then prescribing a top-up transfusion soon after birth for babies with lower than average hemoglobin (who are known to be at higher risk of various adverse outcomes) [9] may be justified, especially for the babies for whom DCC has been precluded by maternal or fetal conditions. These include significant maternal bleeding, and monochorionic twins, where deferred cord clamping in the first twin could lead to one twin losing blood to the other. However, if it is the effects on improving cardiovascular stability in the first minutes (with consequential benefits for cardiorespiratory function and reducing severity of illness during the subsequent neonatal intensive care unit (NICU) stay), regardless of the magnitude of transfusion, then early top-up transfusion is unlikely to be helpful.

Observational studies suggest that exposure to blood transfusion itself is harmful to preterm babies, increasing the risk of adverse outcomes [10]. However, this suggestion has not been supported by the small number (to date) of randomized controlled trials of blood (red cell) transfusion thresholds [11-14]. It is unlikely to be the means by which DCC reduced deaths in the largest trial to date of deferred cord clamping in preterm babies, the Australian Placental Transfusion Study (APTS), and in the most recent systematic review on this, because neither showed a difference in rates of other adverse outcomes [6,15].

Another possibility is that it is the umbilical cord blood stem cells received by the baby are the main reason for the observed benefits to both survival and reduced requirement for later blood transfusion [16]. Umbilical cord blood has been demonstrated to be such a good contributor to hematopoiesis that it is a recognized stem cell resource for pediatric and adult hematopoietic stem cell transplant [17]. In addition, umbilical cord blood is a potential regenerative and immunomodulatory agent for a variety of clinical conditions [18], so in this case, the extent of placental transfusion would be critical to the improvement of outcomes, and transfusion with adult red cells would not suffice. There are no established methods to quantify the contribution of umbilical cord stem cells to placental transfusion. However, a larger volume of placental transfusion results in the baby receiving more nucleated cells [19], including more umbilical cord stem cells.

Discerning whether these effects (initial enhanced cardiovascular stability leading to early and sustained reduction in severity of illness or volume of placental transfusion) appear to be the main driver of improved outcomes is likely to contribute to practice change, as well as to informing the design of future research studies into methods to improve outcomes of high-risk newborn babies and reduce their transfusion dependence.

The causal mechanisms of reduced transfusion requirements found in DCC relative to ICC are yet to be resolved. The aim of the study is to address the question; In preterm infants (P) does DCC (I) compared to ICC (C) reduce dependence on red cell transfusion via enhanced cardiovascular stability (mediator 1, M1) or via an increased volume of placental transfusion (M2).

The study is a nested retrospective study, called the Transfusions in the APTS Newborns Study (TITANS) (study registration: ACTRN12620000195954), of the cohort of babies who were enrolled and randomly assigned to ICC or DCC in the Australian and New Zealand (NZ) sites for APTS (study registration: ACTRN12610000633088). This design has been developed to take advantage of the comprehensive dataset already collected for APTS, and because there is currently no suitable prospective study that could address the same research questions in such a large group of participants.

Babies had been considered eligible for APTS if obstetricians or maternal-fetal medicine specialists anticipated that delivery would occur before 30 weeks of gestation. Exclusion criteria included fetal hemolytic disease, hydrops fetalis, twin-twin transfusion, genetic syndromes, and potentially lethal malformations. Further details are available in the original APTS publication [15]. In the present TITANS analysis, we will also exclude any baby with a diagnosis of hemolytic anemia or aplastic/hypoplastic anemia.

There were 1401 babies enrolled for APTS from the 13 Australian and 5 NZ hospital sites [15]. APTS data was provided to the TITANS team on 31 July, 2020. It is planned to collect additional data from Australian and NZ APTS sites using a customised, secure web-based database application (REDCap) [20], which is maintained by the University of Sydney, Sydney, Australia. Data will be obtained from source documents (patient hospital records and laboratory reports) using the electronic data collection application from each study site. The individual participant data collected will correspond to the minimum data required to answer the research questions. Baby identification (ID) and other babies details from APTS will be used to re-identify participants and link them to hospital records. Identified data will be collected, in order to allow linkage between the data newly collected from patient records and hospital laboratories and the existing APTS dataset. The data will be checked with respect to range, internal consistency, consistency with published reports and missing items. After data cleaning and analysis, data will be stored in re-identifiable form, with each participants data being identified with the same study numbering system as used for the APTS study.

We will combine the data already extracted, stored and cleaned from APTS with the additional data obtained from study sites for each participating baby, to determine which factors are most influential in reducing transfusion requirements. The specific objectives are, after adjustment for prior risk factors (listed below), to determine:

1.Whether the effect of the intervention (cord clamping) on the outcome (blood transfusions) is mediated by placental transfusion (measured by hematocrit (Hct)) as seen in Figure 1 (a, c) following the causal path X M1 Y, where X is the intervention, ICC or DCC, Y is the outcome, mediator M1 is placental transfusion, and M2 is initial severity of illness stability

2.Whether the effect of the intervention (cord clamping) on the outcome (blood transfusions) is mediated by initial severity of illness (respiratory support, sampling line yes/no and total duration number, blood pressure, cumulative blood sample volume) as seen in Figure 1 (b, c) following the causal path X M2 Y

3.Whether the effect of cord clamping intervention on the outcome (blood transfusions) is driven by multiple mediators (placental transfusion and initial severity of illness) as seen in Figure 1 (c)

4.Whether cording clamping intervention (ICC or DCC) has a direct effect on the outcome after accounting for the mediators as seen in all panels of Figure 1: X Y.

The protocol was approved by the Northern Sydney Local Health District Human Research Ethics Committee in November 2019 (Version 3.0, Reference 2019/ETH12819), the Mater Misericordiae Ltd Human Research Ethics Committee (Version 1.0, Reference HREC/MML/56247), the Mercy Health Human Research Ethics Committee (Version 2.0, Reference 2020-078), and the Southern Health and Disability Ethics Committee (Version 1.0, Reference 19/STH/195). The ethics committees have granted a waiver of consent. The study is conducted in accordance with the National Health and Medical Research Council Statement on Ethical Conduct in Research Involving Humans.

Intervention

The intervention consisted of either immediate or delayed cord clamping (as assigned in APTS). Immediate clamping was defined as clamping the cord within 10 seconds of delivery. Delayed clamping was defined as clamping the cord at least 60 seconds after delivery, with the infant held as low as possible, below the introitus or placenta, and with no palpation of the cord. Variations in the protocol were allowed if they would aid the mother, baby, or both. If the baby was non-vigorous (heart rate <100 beats per minute, low muscle tone, or lack of breathing, or crying), clinicians were allowed to break protocol using their discretion. Cord milking was not part of the protocol for either intervention. Further details may be sourced from the original APTS publication [15].

Outcomes

The primary outcome is the proportion of babies receiving red cell transfusion (for restoration of hemoglobin or blood volume). The secondary outcomes are number of transfusions per baby, cumulative transfusion volume (mL/kg) per baby, and primary reasons for each transfusion.

Putative Mediators

M1: Indicators of placental transfusion to be assessed will be hematocrit (on admission, highest on the first day, highest in the first week collected before any postnatal transfusion).

M2: Indicators of initial severity of illness to be assessed will be cumulative blood sample volume collected throughout hospital stay (number of blood tests multiplied by hospitals usual sample volume for each type of test), sampling line (umbilical arterial line or peripheral arterial line) - yes/no and total duration, mechanical ventilation or inspired O2, and blood pressure.

Sensitivity Analyses (For the Primary Outcome Analysis Only)

Sensitivity analyses will adjust for the following variables: gender, birth <27 weeks vs. 27 weeks, method of delivery (vaginal versus cesarean), intraventricular hemorrhage (IVH) (yes/no and grade III/IV yes/no), surgery for patent ductus arteriosus (PDA), necrotizing enterocolitis (NEC), and sodium in the first 24 hours of life. We will also test model assumptions relating to sequential ignorability and post-randomization confounding (discussed further in the data analysis plan).

Potential Confounders (Covariates)

The following covariates may be used for adjustment in the analysis: gestational age at randomization before birth and any oral iron supplement pre-transfusion.

Timing of Assessments

Putative mediating variables will only be analyzed if they have been measured before the outcome and will be excluded if there is not adequate time and date information available. If the multiple mediator model is applied, careful consideration of timing information will be evaluated. If there is insufficient empirical information to conclude the causal ordering of mediators (M1 causes M2), we will adjust our analytic approach (as discussed in the analysis plan) and discuss any limitations.

Data Analysis Plan

The analysis will include all babies who were initially randomized in the APTS trial for whom we were able to obtain the relevant data and be based on intention-to-treat. All statistical analyses will be conducted in R version 4.1.3 (2022-03-10; R Foundation for Statistical Computing, Vienna, Austria). Descriptive characteristics for continuous data will be presented as means or medians, as appropriate, and categorical data will be presented as frequencies and percentages.

A model-based inference approach will be applied to estimate the average causal mediation effect (ACME), average direct effect (ADE), and the average total effect as recommended [23-25]. This approach will be applied with the R mediation package [26]. We will initially fit two models, one model with mediation as the dependent variable and intervention as the independent variable (mediator model), and a second model with the outcome as the dependent variable, and both mediation and intervention as independent variables (outcome model). To account for the clustering of multiples, estimates will be calculated with generalized estimating equations with a compound symmetric correlation structure to account for within subject correlations. Depending on the outcome (binary, count, skew) these will be modelled with the appropriate family and link functions.

A counterfactual framework will be applied to the mediator and outcome models to simulate the values of the mediator and outcome to estimate the potential values of the mediator. This process is used to estimate the ACME, ADE, and average total effects; 95%CI will be estimated with 1000 bootstrap simulations.

We will apply single mediator models on both placental transfusion variables and initial severity of illness variables if mediators are statistically independent, as seen in Table 1. Independence will be tested using linear regression and any appropriate link functions. If both mediators are not statistically independent, we will investigate the possibility of multiple mediator models, which require an expanded framework for analysis [21]. Here we assume that initial severity of illness is causally related to placental transfusion. For this process, we will use the method developed by Imai and Yamamoto [21] to estimate the ACME and ADE. Following this, 95%CI will be estimated with 1000 bootstrap simulations. If theoretical and empirical timing data and sensitivity analyses suggest that M1 and M2 have non-causal correlation and may be affected by an unmeasured latent mediator, we will adjust our approach to estimate interventional direct and path-specific indirect effects [27,28].

Sensitivity analyses have been limited to a set of biologically plausible and clinically meaningful groups that will be explored by including them for adjustment with covariates, and with the introduction of interaction terms if appropriate. Missing data will be described, reasons for missing data will be explored, and the impact of missing data on conclusions about the treatment effect on the primary outcome will also be explored where possible (e.g., using sensitivity analyses and multiple imputation techniques).

Methodological Assumptions

The causal mediation approach assumes sequential ignorability: that the treatment effect on the outcome is not confounding and that the mediator effect on the outcome is not confounded. As treatment was randomly allocated to neonates, we will assume that the treatment-mediator relationship is not confounded. However, the mediator itself has not been randomized. Thus, unknown confounders may be driving a spurious effect in the mediator-outcome relationship. We will employ additional sensitivity analyses to estimate whether any mediation effects are sensitive to the violation of the assumption of sequential ignorability. To test the possibility of unmeasured confounders we will examine the correlation between residuals in the mediator model and the outcome model. If there is no correlation this would suggest there is no unmeasured confounding, if there is correlation between the residuals, an unmeasured mediator may be affecting both the measured mediator and the outcome. We will apply the method developed by Imai et al. andTingley et al. [23,26] that uses sensitivity analyses to evaluate if the ACME estimate is sensitive to unmeasured confounding.

Post-randomization confounders are dependent on the treatment allocated, affect both mediator and outcome, and can corrupt the mediation estimate. In the context of the present trial, it is possible that non-adherence to the intervention is a post-randomization confounder. We are analyzing our data based on intention to treat principles; however, a sensitivity analysis based on the actual time of cord clamping to assess the influence of non-adherence with the treatment protocol on our estimates may be performed.

Blood transfusions of neonates have been associated with a number of serious adverse outcomes [29]. Nevertheless, there are few evidence-based methods to reduce transfusion exposure [30]. The APTS study found that DCC was associated with a statistically significant reduced need for red cell transfusions by about 10% compared to ICC [15]. However, the mechanism remains unclear.

The study will, at a minimum, provide further information that should increase clinicians understanding of the pathways by which DCC (or other methods to accomplish placental transfusion) results in beneficial patient outcomes. Since one of the main barriers to implementation is lack of understanding about the mechanisms by which such a simple practice change should have such dramatic effects, this should improve adherence to recommendations to defer cord clamping for most babies, thereby reducing mortality and transfusion incidence.

By elaborating on the mechanisms, it may also provide good evidence for how other routine neonatal intensive care practices and interventions affect likelihood of needing to transfuse. Better understanding of these effects may lead to other testable hypotheses or improvements in other aspects of practice, further reducing transfusion exposure and improving other outcomes.

Potential limitations of the study include the dependence on some routinely collected clinical data, which were not collected at the time by the original study according to predefined research definitions. However, we have no reason to think that potential problems of data quality would have been influenced by study group allocation and so do not anticipate that this will be a source of bias.

Originally posted here:
Protocol for a Nested, Retrospective Study of the Australian Placental Transfusion Study Cohort - Cureus

A bone marrow transplant is a medical procedure that replacesthe bone marrow with healthy cells. Replacement cells might come from either ones own body or from a donor. A stem cell transplant, or more specifically, a hematopoietic stem cell transplant, is another name for a bone marrow transplant. Transplantation can be used to treat leukemia, myeloma, and lymphoma, as well as other blood and immune system illnesses that impact the bone marrow. Cancer and cancer treatment can damage the hematopoietic stem cells. Hematopoietic stem cells are blood-forming stem cells. Hematopoietic stem cells that are damaged may not develop into red blood cells, white blood cells, or platelets. These blood cells are vital, and each one serves a specific purpose. A bone marrow transplant can help the body regenerate the red blood cells, white blood cells, and platelets it requires.

The global Bone Marrow Transplant market is estimated to be valued at $10,356.1 Mn Mn in 2021 and is expected to exhibit a CAGR of 4.0% over the forecast period (2022-2028).

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The study provides data on the most exact revenue estimates for the complete market and its segments to aid industry leaders and new participants in this market. The purpose of this study is to help stakeholders better understand the competitive landscape and design suitable go-to-market strategies. The market size, features, and growth of theBone Marrow Transplantindustry are segmented by type, application, and consumption area in this study. Furthermore, key sections of the GlobalBone Marrow Transplantmarket are evaluated based on their performance, such as cost of production, dispatch, application, volume of usage, and arrangement.

Competitive Analysis: Global Bone Marrow Transplant Market

Detailed Segmentation:

By Type:

By Treatment Type:

:

: United States, Canada, and Mexico & : Argentina, Chile, Brazil and Others & : Saudi Arabia, UAE, Israel, Turkey, Egypt, South Africa & Rest of MEA. : UK, France, Italy, Germany, Spain, BeNeLux, Russia, NORDIC Nations and Rest of Europe. -: India, China, Japan, South Korea, Indonesia, Thailand, Singapore, Australia and Rest of APAC.

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Key Drivers & Barriers:

This report has looked at high-impact rendering elements and causes to help readers comprehend the overall trend. Furthermore, the report contains constraints and obstacles that may operate as roadblocks for the players. This will enable people to pay attention and make well-informed business judgments. Specialists have also focused on future business opportunities.

Competitive Outlook:

Company profiles, revenue sharing, and SWOT analyses of the major players in theBone Marrow TransplantMarket are also included in the research. TheBone Marrow Transplantindustry research offers a thorough examination of the key aspects that are changing, allowing you to stay ahead of the competition. These market measuring methods assist in the identification of market drivers, constraints, weaknesses, opportunities, and threats in the global market.

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Use of current statistics gathered by our own researchers. These provide you historical and projected data that is evaluated to inform you why theBone Marrow TransplantMarket is changing this allows you to anticipate market changes and stay ahead of your competition.

Youll be able to quickly pinpoint the information you need thanks to the concise analysis, clear graph, and table style.

Denotes the area and market segment that is likely to expand the fastest and dominate the market.

A geographical analysis showing the consumption of the product/service in each region as well as the variables impacting the market within each region

Comprehensive company profiles for the major market players, including company overviews, company insights, product benchmarking, and SWOT analysis for the major market players, as well as new service/product launches, partnerships, business expansions, and acquisitions in the last five years of companies profiled.

The industrys present and future market outlook, including recent changes such as growth possibilities and drivers, as well as challenges and restraints in both emerging and developed markets.

Porters five forces analysis is used to provide an in-depth examination of the market from numerous angles.

Provides industry understanding via Value Chain Market Dynamics scenario, as well as market development potential in the next years

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Increasing efforts to set up centers for Bone Marrow Transplant is expected to Boost the growth of the market, Top Key players | Lonza, Merck KgaA,...

Cell membrane-coated nanoparticles, applied in targeted drug delivery strategies, combine the intrinsic advantages of synthetic nanoparticles and cell membranes. Although stem cell-based delivery systems were highlighted for their targeting capability in tumor therapy, inappropriate stem cells may promote tumor growth.

Study:Stem cell membrane-camouflaged targeted delivery system in tumor. Image Credit:pinkeyes/Shutterstock.com

A review published in the journalMaterials Today Biosummarized the role of stem cell membrane-camouflaged targeted delivery system in tumor therapy and focused on the underlying mechanisms of stem cell homing toward target tumors. Nanoparticle-coated stem cell membranes have enhanced targetability, biocompatibility, and drug loading capacity.

Furthermore, the clinical applications of induced pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) were investigated as membrane-camouflaged targeted delivery systems for their anti-tumor therapies. In concurrence, the stem cell membrane-coated nanoparticles have immense prospects in tumor therapy.

Cell-based targeted delivery systems have low immunogenicity and toxicity, innate targeting capability, ability to integrate receptors, and long circulation time. Cells such as red blood cells, platelets, stem cells, tumor cells, immune cells, and even viral/bacterial cells can serve as effective natural vesicles.

MSCs derived from the umbilical cord (UC-MSCs), bone marrow (BM-MSCs), and adipose tissue (ATMSCs) are utilized in clinical applications. However, iPSCs are preferable over MSCs in clinical applications due to their easy fetch by transcription factor-based reprogramming of differentiation of somatic cells.

Stem cells (MSCs/ iPSCs) can be easily isolated and used as drug delivery systems for tumor therapy. Stem cell-based delivery systems have inflammation or tumor lesions targeting capacity. However, stem cells are often entrapped in the lung due to their size, resulting in microembolism.

Cell membrane-coated nanoparticles are applied in targeted delivery strategies. To this end, stem cell membrane-coated nanoparticles have tremendous prospects in biomedical applications. Although previous reports mentioned the role of cell membrane-coated nanocarriers in tumor therapy, delivery systems based on stem cell membranes have not been explored extensively.

Stem cell membrane-coated nanoparticles obtained from stem cells have complex functioning and can achieve biological interfacing. Consequently, stem cell membrane-coated nanoparticles served as novel drug delivery systems that could effectively target the tumor.

Previous reports mentioned the preparation of doxorubicin (DOX) loaded, poly (lactic-co-glycolic acid) (PLGA) coated MSC membrane-based nanovesicles, which showed higher cellular uptake than their PLGA uncoated counterparts. Similarly, the DOX-loaded MSC membrane-coated gelatin nanogels showed enhanced storage stability and sustained drug release.

Thus, the stem cell membrane-coated nanoparticles served as novel carriers for stem cells and facilitated the targeted delivery of the drugs at the tumor site. Since the stem cell membrane-coated nanoparticles had good targeting and penetration abilities, they enhanced the efficiency of chemotherapeutic agents in tumor therapy and minimized the side effects.

Reactive oxygen species (ROS) based photodynamic therapy (PDT) is mediated by photosensitizers with laser irradiations. Previous reports mentioned the development of MSC membrane-based mesoporous silica up-conversion ([emailprotected]2) nanoparticles that efficiently targeted the tumor due to their high affinity after being coated with MSC membrane.

These cell membrane-coated nanoparticles showed high cytocompatibility (with hepatocyte cells) and hemocompatibility (with blood). Moreover, the [emailprotected]2 nanoparticles-based PDT therapy under 980-nanometer laser irradiations could inhibit the tumors in vivo and in vitro. Consequently, the stem cell membrane-coated nanoparticles had circulation for an extended time and escaped the immune system, thereby increasing their accumulation at the tumor site.

Stem cell membrane-coated nanoparticles were also applied to deliver small interfering RNA (siRNA) via magnetic hyperthermia therapy and imaging. Previous reports mentioned the preparation of superparamagnetic iron oxide (SPIO) nanoparticles using an MSC membrane that reduced the immune response.

Additionally, the CD44 adhesion receptors were preserved on the surface of the MSC membrane during preparation. These prepared nanovesicles were unrecognized by macrophages, which enabled their stability in blood circulation. The nanosize and tumor homing capacity of MSCs helped the nanovesicles generate a dark contrast in T2-weight magnetic resonance imaging (MRI).

Cell membrane-coated nanoparticles helped fabricate various targeted delivery strategies. Especially, stem cell membrane-coated nanoparticles have the following advantages: stem cells are easy to isolate and expand in vitro. Thus, multilineage potential and phenotypes could be preserved for more than 50 population doublings in vitro.

Stem cell membrane-coated nanoparticles also have an intrinsic capacity to target inflammation or tumor lesions. Hence, these nanoparticles were established for tumor therapy, building a strong foundation for stem cell membrane-mediated delivery systems.

On the other hand, stem cell membrane-coated nanoparticles have the following drawbacks: Despite various sources for collecting MSCs (UC-MSCs/BM-MSCs/ATMSCs), the number of cells obtained is limited, although iPSCs are relatively easy to fetch by reprogramming differentiated somatic cells, the reprogramming is a high-cost step, restricting the clinical applications of iPSCs.

Zhang, W., Huang, X. (2022). Stem cell membrane-camouflaged targeted delivery system in tumor. Materials Today Bio.https://www.sciencedirect.com/science/article/pii/S2590006422001752

Disclaimer: The views expressed here are those of the author expressed in their private capacity and do not necessarily represent the views of AZoM.com Limited T/A AZoNetwork the owner and operator of this website. This disclaimer forms part of the Terms and conditions of use of this website.

Link:
Stem Cell Membrane-Coated Nanoparticles in Tumor Therapy - AZoNano

HAEMOGLOBIN IS a protein in your red blood cells. Your red blood cells carry oxygen throughout your body. If you have a condition that affects your bodys ability to make red blood cells, your haemoglobin levels may drop. Low haemoglobin levels may be a symptom of several conditions, including different kinds of anaemia and cancer.

If a disease or condition affects your bodys ability to produce red blood cells, your haemoglobin levels may drop. When your haemoglobin level is low, it means your body is not getting enough oxygen, making you feel very tired and weak.

Normal haemoglobin levels are different for men and women. For men, a normal level ranges between 14.0 grams per decilitre (gm/dL) and 17.5 gm/dL. For women, a normal level ranges between 12.3 gm/dL and 15.3 gm/dL. A severe low-haemoglobin level for men is 13.5 gm/dL or lower. For women, a severe low haemoglobin level is 12 gm/dL.

Your doctor diagnoses low haemoglobin by taking samples of your blood and measuring the amount of haemoglobin in it. This is a haemoglobin test. They may also analyse different types of haemoglobin in your red blood cells, or haemoglobin electrophoresis.

Several factors affect haemoglobin levels and the following situations may be among them:

Your body produces red blood cells and white blood cells in your bone marrow. Sometimes, conditions and diseases affect your bone marrows ability to produce or support enough red blood cells.

Your body produces enough red blood cells, but the cells are dying faster than your body can replace them.

You are losing blood from injury or illness. You lose iron any time you lose blood. Sometimes, women have low haemoglobin levels when they have their periods. You may also lose blood if you have internal bleeding, such as a bleeding ulcer.

Your body cannot absorb iron, which affects your bodys ability to develop red blood cells.

You are not getting enough essential nutrients like iron and vitamins B12 and B9.

Your bone marrow produces red blood cells. Diseases, conditions and other factors that affect red blood cell production include:

Lymphoma: This is a term for cancers in your lymphatic system. If you have lymphoma cells in your bone marrow, those cells can crowd out red blood cells, reducing the number of red blood cells.

Leukaemia: This is cancer of your blood and bone marrow. Leukaemia cells in your bone marrow can limit the number of red blood cells your bone marrow produces.

Anaemia: There are many kinds of anaemias involving low-haemoglobin levels. For example, if you have aplastic anaemia, the stem cells in your bone marrow dont create enough blood cells. In pernicious anaemia, an autoimmune disorder keeps your body from absorbing vitamin B12. Without enough B12, your body produces fewer red blood cells.

Multiple Myeloma: This causes your body to develop abnormal plasma cells that may displace red blood cells.

Chronic Kidney Disease: Your kidneys dont produce the hormone that signals to your bone marrow to make red blood cells. Chronic kidney disease affects this process.

Antiretroviral medications: These medications treat certain viruses. Sometimes these medications damage your bone marrow, affecting its ability to make enough red blood cells.

Chemotherapy: Chemotherapy may affect bone marrow cells, reducing the number of red blood cells your bone marrow produces.

Doctors treat low haemoglobin by diagnosing the underlying cause. For example, if your haemoglobin levels are low, your healthcare provider may do tests that reveal you have iron-deficiency anaemia. If that is your situation, they will treat your anaemia with supplements. They may recommend that you try to follow an iron-rich diet. In most cases, treating the underlying cause of anaemia will bring the haemoglobin level up.

Many things can cause low haemoglobin, and most of the time you cannot manage low haemoglobin on your own. But eating a vitamin-rich diet can help maintain your red blood cells. Generally, a balanced diet with a focus on important nutrients is the best way to maintain healthy red blood cells and haemoglobin.

keisha.hill@gleanerjm.comSOURCE: Centres for Disease Control and Prevention

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Factors that affect haemoglobin levels and how to detect when it's low - Jamaica Gleaner

The media continues the one-handed count of patients that seem to be cured of HIV as a man who has lived with the disease since the 1980s has been in remission for 17 months.

The story is always the samethey seem to be cured, and they get a cool nicknamein this case the City of Hope Patient, after Duarte, California, where he was treated.

The difference in this case was the treatmenta bone marrow transplant to treat blood cancer leukemia from a donor who was naturally resistant to the virus.

The most remarkable difference however, is that he is only patient cured of HIV by coincidence.

The man had developed leukemia, and took the bone marrow transplant for that reason. As it happened, the donor was resistant to HIV, and taught the mans body to create an immune response against the virus.

RELATED: Worlds Second Person Cured of HIV: 40-Year-old Man is Confirmed to Be 30 Months Virus-Free

This is also the first one who got it during the epidemic of HIV/AIDS that took so many lives.

When I was diagnosed with HIV in 1988, like many others, I thought it was a death sentence, said the City of Hope Patient. I never thought I would live to see the day that I no longer have HIV.

SIMILAR: Two Patients Make History After Essentially Being Cured of HIV Using Stem Cell Transplant

So far, only three people have been seemingly cured of human immunodeficiency virus (HIV) which weakens the bodys immune system and leads to the more severe AIDS (autoimmune deficiency syndrome) which can be lethal.

The man no longer takes antiretroviral drugs, the only treatment for HIV. A bone marrow transplant is not a likely future cure, do to it being a tricky and side-effectual procedure.

Nevertheless, all cure cases have been those where a patient is given a transplant of some kind, mostly stem cells, that contain the very rarely occurring natural immunity to the virus.

The case was reported at the AIDS 2022 conference in Montreal, Canada.

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Fourth Patient Seemingly Cured of HIV Through Wild Coincidence - Good News Network

Type 1 diabetes (T1D) is a chronic immune-mediated disease characterized by the destruction of pancreatic -cells, resulting in absolute insulin deficiency and hyperglycemia. It is primarily a disease of youth, accounting for approximately 85% of cases in people under the age of 20 and 5% to 10% of all diagnosed cases of diabetes [1,2]. Although the exact mechanisms are unknown, T1D is thought to develop through immune system activation against -cell antigens and the initiation of proinflammatory cytokine responses. Environmental factors, obesity, viral infections, and nutritional factors were found to play a role in the pathophysiology as well [3]. T1D predisposes to a number of comorbidities, such as obesity, chronic kidney disease, metabolic syndrome, coronary artery disease, and hypertension. Such predispositions may account for higher mortality rates, affecting up to one in 10 adult patients within a year of diagnosis [4]. In fact, diabetic nephropathy (DN) is said to account for up to 40% of end-stage renal disease (ESRD) cases worldwide. Cardiovascular events account for up to 70% of T1D deaths and are 10 times more common in diabetics than in non-diabetics [5]. Therefore, it is critical to focus on novel therapies that aim to reduce the risks of acute complications such as hypoglycemia and diabetic ketoacidosis (DKA) while avoiding long-term complications such as DN, neuropathy, and retinopathy [5].

Exogenous insulin is currently the most prevalent treatment for T1D. Although exogenous insulin administration may be life-saving, it is not a cure for the disease. If patients are unable to maintain tight glycemic control by strictly adhering to their insulin regimen, they will invariably develop severe secondary complications that may shorten their life span [6]. Exogenous insulin is not a viable substitute for normal pancreatic islet function, mainly due to the absence of accurate temporal glucose control over time [7]. The administration of insulin can also result in hypoglycemic episodes [6]. A cross-sectional study conducted in Mexico revealed that patients' fear of hypoglycemic episodes prevented them from complying with their insulin treatment plan [8].

Replacement of the defective insulin-producing cells (IPC) is yet another potential therapy for T1D. This is possible through transplantation of the pancreas. Since the first pancreatic transplant took place in 1966, over 50,000 such transplants have been performed worldwide. Patients with T1D who receive a pancreatic transplant were found to have a reduced risk of subsequent complications and a longer life expectancy [9]. However, since transplantation is a major surgical procedure, patients must be fit for surgery [6]. Transplants necessitate permanent immunosuppression, which may put patients at risk for a variety of infections. In addition, they are associated with a number of postoperative complications, such as pancreatitis, due to low tolerance to cold ischemia, bleeding, thrombosis, and anastomotic leakage, which may require relaparotomy and graft pancreatectomy in recipients [9].

An alternative to pancreatic transplantation that is both safe and effective is islet cell transplantation. Scharp et al. published the first case of allogeneic intraportal islet transplantation for T1D in 1990, which led to short-term insulin independence and paved the way for clinical islet transplantation [10]. Despite the fact that the immunosuppressive regimen reported from Edmonton, Canada, also known as the Edmonton protocol (the Edmonton protocol introduced significant adjustments to the transplantation procedure, including the use of an immunosuppressive regimen free of steroids and the transplanting of an average islet mass of 11,000 islet equivalents per kilogram) has achieved unprecedented success in islet transplantation in terms of insulin independence, a number of factors continue to influence the outcome of this minimally invasive procedure [11]. Islet cell transplantation can induce a rapid inflammatory reaction in the circulation, leading to the loss of the vast majority of transplanted islets. The use of large doses of immunosuppressants during transplantation compromises the long-term viability and function of the graft, and the need for long-term immunosuppressive medications after the transplant poses a risk of organ damage, malignancies, new infections, and new-onset T1D in patients [12]. The high cost of islet transplantation and the paucity of human cadaveric islets highlight the urgent need for innovative pancreatic islet transplantation procedures [7]. This is where stem cells (SCs) pose an important role.

SCs are a highly promising novel treatment for T1D due to their ability to differentiate into several cell types and their regenerative potential. SCs can be categorized into four basic groups based on their origin as shown in Figure 1.

Mesenchymal stem cells (MSCs), also called mesenchymal stromal cells, are non-hematopoietic, multipotent SCs. They can be extracted from a variety of sources, including bone marrow, liver, kidney, adipose tissue, urine, umbilical cord blood, umbilical tissue, Wharton's jelly, placenta, and even endometrial tissue (menstrual blood-derived endometrial stem cells - MenSC). Several surface markers, including CD73, CD90, and CD105, can be utilized to identify MSCs. Due to their ability to differentiate into numerous cell types, they can be used to repopulate damaged tissues [13,14]. MSCs have gained enormous popularity in the treatment of T1D because of their ability to regulate fibrosis and tissue regeneration, as well as their ability to modulate immunological function. In addition, they produce a variety of secretory molecules, such as cytokines and exosomes, which play an essential role in the treatment of T1D [15]. Studies on animals treated with MSCs have shown a significant reduction in hyperglycemia, as evaluated by a decrease in serum glucose and an increase in insulin and C-peptide levels. In addition, they were able to restore normal levels of lipid fractions. Using MSCs lowered the serum levels of both liver and kidney function markers in diabetic rats, demonstrating their hepato-renal protective benefits in T1D [16].

Several mechanisms have been discovered to play a role in the management of T1D by MSCs (Figure 2).

MSCs, such as bone marrow stromal cells, promote angiogenesis through the secretion of cytokines such as basic fibroblast growth factor and vascular endothelial growth factor (VEGF) [17]. In addition, they play a crucial role in immunomodulation by moving to areas of inflammation and modifying the phenotype of dendritic cells (DC), T cells, B cells, and natural killer cells. They downregulate proinflammatory cytokines and escape CD8+ T cell-mediated apoptosis, inhibit maturation of DC, while reducing T-lymphocyte proliferation via transforming growth factor-beta 1 (TGF-1), hepatocyte growth factor, and nitric oxide. By stimulating the production of regulatory T cells, TGF-1 plays a significant role in the immunomodulation of MSCs. MSCs have also been found to improve the function, survival, and graft outcome of neonatal porcine islets by increasing the expression of genes involved in the formation of endocrine cells, insulin, and platelet-derived growth factor alpha (PDGFR-). PDGFR- suppresses Notch 1 signaling (Notch 1 downregulates transcription factors involved in the formation of endocrine cells and insulin), resulting in the maturation and development of islet cells [18]. Zhou et al. discovered that wild-type p53-induced phosphatase 1 (a serine/threonine phosphatase) regulates the immunomodulatory properties of MSCs via the expression of interferon-alpha and bone marrow stromal cell antigen 2, consequently playing an important role in the therapeutic effects of MSCs in T1D [19].

Even though studies have shown that MSCs are capable of reconfiguring the immune system, they must be rescued to some extent from immune-mediated destruction, indicating that immunomodulation will be necessary even if a viable MSCs therapy for T1D is produced [20]. When using -cells from an allogeneic stem cell source, an alloreactive response to donor antigens will be generated unless we obtain SCs from the patient's own cells. To circumvent this, researchers have investigated encapsulation strategies employing semipermeable immune barriers to provide immune shielding and prevent graft rejection [21]. Some studies have also demonstrated that the use of suicide genes together with stem cell transplants promotes functional immune reconstitution and thereby prevents graft-versus-host disease in patients [22].

It has been demonstrated that MSCs undergo apoptosis in the circulation of the host or in engrafted tissues following delivery to the patient's body, which plays a significant part in their therapeutic role in T1D. During the execution of apoptosis, apoptotic extracellular vesicles (apoEVs), formerly known as apoptotic bodies, have emerged as regulators of numerous biological processes, as opposed to being only debris. Specifically, apoEVs have been shown to regulate T cell and macrophage immunological function as well as stimulate tissue repair, including skin regeneration and vascular protection [23].

This game-changing discovery of MSCs in the treatment of T1D has propelled biological sciences to a new level of sophistication, allowing for the manipulation of cell fate and the cultivation of higher-order cellular structures. However, there is still a huge gap regarding its application in actual clinical practice.

We were only able to find 12 clinical trials on PubMed that evaluated the use of MSCs in the treatment of T1D. Ten of the 12 studies were undertaken in Asia, primarily in China and India. To date, the exact pathogenesis of T1D is not fully understood. Genetic factors have been found to play a role in the development of T1D, which may have affected the outcomes of previous clinical trials. Therefore, conducting multiple different studies worldwide would not only enable us to identify the effects of ethnicity and genetics on the response to MSC therapy in T1D patientsbut also help us to generalize the efficacy of MSCs to the entire population. In order to achieve the best outcomes while using medications to treat T1D, it is also crucial to perform additional research to more clearly identify the pathophysiology of T1D.

In the course of studying the patient selection criteria utilized in clinical trials, we made a fascinating discovery. We found that every clinical study had excluded patients with immunosuppression, viral illnesses such as hepatitis B and C, comorbidities including hematologic diseases, rheumatologic diseases, and kidney diseases, and pregnant patients, all of which could have influenced the results of the studies. Our present understanding of the action of apoEVs, as described by Fu et al., leads us to believe that in order for MSCs to undergo apoptosis, their recipients must be able to initiate apoptotic activity [23]. In order for this to occur, patients must have a particular number of cytotoxic T cells or natural killer cells; hence, patients who do not meet this criterion are unlikely to benefit from MSC delivery. To further elucidate the mechanisms of action of MSCs, it is essential to undertake additional studies with immunosuppressed patients in order to identify the optimal cohort of T1D patients for MSC therapy. In addition, further clinical research should be conducted to uncover the apoptotic signals that stimulate tissue regeneration and angiogenesis, as recognizing these signals would allow us to utilize a channel in parenchymal tissue to increase its regeneration capacity.

We also observed that the majority of trials exclusively enrolled patients with recent-onset T1D. A study conducted in Iran revealed that early transplantation of MSCs resulted in superior outcomes for T1D patients compared to late transplantation. This may be due to the honeymoon phase of diabetes, which may have obscured the effects of MSCs in these studies [24]. The honeymoon phase is the period during which a person with T1D appears to improve and may only require minimal amounts of insulin or experience normal or near-normal blood sugar levels without insulin. To extrapolate the results to a larger population and unmask the effects of the honeymoon period, it is necessary to conduct trials on patients with late-onset T1D.

To date, the exact mechanism by which MSCs contribute to the remission of T1D has not been identified; therefore, further research is required to get a better knowledge of mechanisms such as immunomodulation, homing, and paracrine signaling of MSCs. It is also vital to undertake studies to discover the appropriate number of MSCs, injection frequency, and optimal infusion route in order to maximize results. Cai et al. concluded that pancreatic arterial transfusion would assist in avoiding the first pass pulmonary effect of MSCs, hence lowering the sequestration of MSCs in the lungs and allowing for optimal results [25].

A few studies have used 3D microspheres to increase the proliferation capacity of MSCs with positive results. However, there is insufficient information available regarding the proliferation capacity, revascularization, efficiency of differentiation, and survival time of MSCs. Therefore, conducting studies to elucidate these aspects of MSC therapy is an urgent necessity. We would also be able to learn more about the graft's survival time and tumorigenic potential if we followed the patients for a longer period of time.

Patient-specific variables such as age, body mass index, lifestyle, socioeconomic status, level of activity, diet, autoimmune status, and drug interactions must be taken into consideration while conducting studies and analyzing data. In order to identify the ideal conditions necessary to create the desired quantities of MSCs to achieve remission of T1D, future research must also incorporate in-depth information regarding external factors that affect the viability of MSCs, such as storage conditions, plating density, and culture media.

In this article, we aim to discuss the role of MSCsderived from various tissues in the treatment of T1D, as well as their feasibility and limitations.

We present a summary of the extraction methods, advantages, limitations, and outcomes from several studies of MSCs derived from various types of tissues.

The majority of umbilical cord tissue-derived stem cells (UC-MSCs) are found in the subcortical endothelium of the umbilical cord, the perivascular area, and Wharton's jelly [26]. According to studies, roughly1 106UC-MSC can be extracted from a 20 cm human umbilical cord [27]. MSCs isolated from Wharton's jelly have been grown for over 80 population doublings without showing any signs of senescence, morphological alterations, an increase in growth rate, or a change in their ability to develop into neurons. Recent research has demonstrated that xenotransplantation of post-differentiated human UC-MSC without immunosuppressive therapy does not result in rejection [28]. This lack of immunogenicity may be attributable to the absence of major histocompatibility II and co-stimulatory molecules such as CD80 (B7-1), CD86 (B7-2), and CD40 [29]. Chao et al. successfully differentiated human UC-MSC into clusters of mature islet-like cells with insulin-producing capacity. In the islet cells, they detected an increase in insulin and other -cell-related genes, including Pdx1, Hlxb9, Nkx2.2, Nkx6.1, and Glut-2. Moreover, they discovered that hyperglycemia in diabetic rats was greatly under control after xenotransplantation of human pancreatic islet-like cell clusters [28]. Patients with newly diagnosed T1D who received repeated intravenous doses of allogeneic UC-MSC showed improved islet cell preservation and a significant rise in postprandial C-peptide levels. However, C-peptide levels did not alter significantly in patients with juvenile-onset T1D. The number of UC-MSC contributed more than other indicators to the prediction of clinical remission, bolstering the evidence of dose-dependent therapeutic efficacy. Therefore, appropriate doses and courses of MSC transplantation should be granted importance in future research [30].

UC-MSC can also be used to treat chronic complications of T1D, such as neuropathy, DN, and retinopathy [31]. Studies have shown that intraperitoneal injection of human UC-MSC can ameliorate renal injury in streptozotocin-induced diabetic mice.[32]. A mice study conducted in China demonstrated that the combination of human UC-MSC and resveratrol can better protect renal podocyte function and the resulting reduction in blood glucose levels and renal damage is superior to those obtained with insulin administration [33]. This suggests that the combination of resveratrol and human UC-MSC may be an innovative technique for treating T1D; however, additional research on humans is necessary to determine the effects of this combination treatment on the management of DN.Another investigation involving mice revealed that UC-MSC therapy restored erectile function by suppressing toll-like receptor 4, alleviating corpora cavernosa fibrosis, and boosting the production of VEGF and endothelial nitric oxide synthase [34]. Nonetheless, a significant advantage of UC-MSC is that they are a rich source of many SCs that can be easily manipulated [27]. They are collected at delivery by clamping and severing the umbilical cord. There are no ethical concerns regarding the use of UC-MSC because the collecting process is non-invasive and retains material that would otherwise be discarded as waste.

Adipose tissue-derived mesenchymal stem cells (ADSCs) are a group of cells that arise from the mesoderm during embryonic development. Amongst several types, subcutaneous adipose tissue seems to be the most clinically relevant source, being available in abundance for harvest, and its isolation only slightly invasive [35,36].

While two major kinds of adipose tissue (white and brown) have been isolated and studied, we focus on white adipose, which produces ADSCs, as brown adipocytes have not yet demonstrated an association with insulin resistance. White adipose tissue expressing uncoupling protein 2 (an isoform of uncoupling protein 1in brown adipose) acts as a storage of excess energy in the form of triglycerides and is thus prone to causing obesity and abnormalities in metabolic pathways such as insulin resistance during hyperplasia [37].

The extracted cell group of interest consists of a putative stem cell population of fibroblast-like cells known as processed lipoaspirate (PLA), found within the stromal compartments of adipose tissue [38]. Obtaining the sample requires lipoaspiration, and although the technique does not negatively affect the function of ADSCs, the vacuum process involved can cause damage to mature adipocytes [37]. Studies have shown that successfully extracted PLA can then differentiate in vitro into multiple cell lineages (including adipogenic, myogenic, chondrogenic, and osteogenic cells), thus providing another source of SCs with multi-germ-line potential instead of the traditional bone marrow-derived MSCs [38-41]. The discovery of the ability of ADSCs to efficiently differentiate into IPC has shed new light on the approach to T1D management [41].

ADSCs utilization can help avoid ethical barriers and tumorigenic complications that are increasingly encountered during stem cell isolation from embryos and induced pluripotent SCs [36]. Yet another advantage of ADSCs for their therapeutic application happens to be the relatively painless procedure and high yields in harvested cell numbers compared to bone marrow procurement [40]. These cells are devoid of human leukocyte antigen-DR expression and therefore have been successfully transplanted via intravenous, intraperitoneal, and renal capsule administration in mice without the need for immunosuppression [36,42].

Insulin replacement therapy with the help of co-transplantation of insulin-secreting ADSCs has been studied as an alternative to lifelong insulin therapy. As with multiple studies, no adverse effects were observed with ADSCs infusion, and in fact, an impressive absence of DKA episodes in all participants was seen [43]. A prospective study conducted in 2015 on 20 patients with T1D found better diabetic control (hemoglobin A1c levels) and sustained improvements in fasting blood sugar, postprandial blood sugar, hemoglobin A1c, and C-peptide levels with the transplantation of autologous insulin-secreting ADSCs [44]. Dantas et al. concluded that combination therapy with ADSCs and Vitamin D (daily cholecalciferol for six months) without immunosuppression was safe, demonstrated immunomodulatory effects, and may play a role in -cell preservation in patients with newly diagnosed T1D [45]. The significant functional and morphological improvements in islet cells as early as two months after transplantation of IPC clusters derived from ADSCs point to the promising nature of this therapeutic approach for achieving target normoglycemia [46,47]. A recent study conducted in 2022 discovered that systemic administration of ADSCs protects male non-obese diabetic (NOD) mice against diabetes induced by programmed death-1 and programmed death-ligand 1 (PD-1/PD-L1) inhibition. Multiple injections of neutralizing antibodies against mouse PD-L1 induce a significant infiltration of immune cells in the islets and a decrease in the -cell area and insulin content of the pancreas. Despite this, systemic ADSCinjection partially protected the pancreas from -cell loss and preserved insulin content, indicating therapeutic potential in T1D [15].

Apart from the therapeutic uses in T1D, the ADSCtherapy has also been shown to reduce adverse effects brought about by complications such as DN and ESRD [48,49]. Inactivation of nuclear factor kappa B pathways and downregulation of VEGF-A, amongst others, are the major mechanisms involved in ameliorating the pathological manifestations of mice with DN [50].

The problem remaining, however, is the inability to become totally free of exogenous insulin. Research suggests that a much larger dose of IPC may be required for a sustained cure of T1D using ADSCs [51]. Therefore, the need of the hour is to conduct further research, placing emphasis on ways to either enhance the production of insulin in IPC derived from ADSCs or alter cell signaling pathways to obtain a greater number of IPC from ADSCs.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are a type of adult stem cell that is abundant in bone marrow and has low immunogenicity [52]. Bone marrow stem cells are broadly categorized into hematopoietic stem cells and MSCs. These cells are sourced from the same individual, potentially minimizing rejection problems and making it a form of therapy for T1D [53]. BM-MSCs can differentiate into functionally competent -cells in vivo, and NOD mouse studies have shown the formation of normal T cell and B cell function, implying that allogeneic bone marrow transplant could prevent islet destruction and restore self-tolerance [54,55]. Because of their well-documented hypoimmunogenic and immunomodulatory properties, BM-MSCs are an appealing therapeutic option for T1D [56].

One study looked at T1D patients with DKA and found BM-MSCs to preserve -cell function in T1D patients, reducing levels of fasting and post-prandial C-peptide levels, with one patient achieving insulin independence for a period of three months [57].

BM-MSCs have been demonstrated to mitigate the effects of metabolic and hepato-renal abnormalities, enhance lipid profiles, and improve carbohydrate and glycemic management. Following an eight-week period of injections with BM-MSCs in diabetic rats, an improvement was observed in their lipid profiles compared to diabetic rats that were not treated with BM-MSCs [16]. In addition, BM-MSCs therapy has been demonstrated to ameliorate diabetes-related liver damage by boosting endogenous hepatocyte regenerative mechanisms and enhancing liver function [58].

BM-MSCs have also been shown to effectively treat comorbidities of T1D, such as DN, poor wound healing, and erectile dysfunction (ED). Nagaishi et al. investigated a novel approach of mixing BM-MSCs with umbilical cord extracts in Wharton's Jelly to enhance the therapeutic effect of ameliorating renal injury in T1D patients with DN. The study demonstrated morphological and functional improvements of diabetes-derived BM-MSC in vitro and a therapeutic impact on DN in vivo, suggesting that this may be beneficial not only for patients with DN but also for patients with other diabetic complications [59]. One study looked to address the problem of impaired epithelial wound healing in T1D patients and found that BM-MSCs promote corneal epithelial wound healing via tumor necrosis factor-inducible gene 6-dependent stem cell activation [60]. Another promising phase I pilot clinical trial found that treating ED in T1D patients with two consecutive intracavernous injections of autologous BM-MSC was safe and effective [61].

Currently, several potential therapeutic approaches are being postulated to approach this issue of T1D from a new viewpoint. Suicide gene therapy is a strategy with potential. This method involves the introduction of suicide-inducing transgenes into the body via BM-MSC. As a result, several processes will be induced, including the suppression of gene expression, the production of intracellular antibodies that block the essential pathways of cells, and the transgenic expression of caspases and deoxyribonucleases. Current clinical trials are examining strategies to restore damaged organs with the use of stem cells as the delivery mechanism [62].

The idea of transplanting BM-MSCs provides patients with hope. Particularly significant are autologous BM-MSC (which are easy to obtain and avoid graft rejection after transplantation) in contrast to allogeneic BM-MSC transplantations, which may result in graft rejection and be accompanied by complications [52]. For stem cell therapy to be most beneficial, early delivery of stem cells following a diagnosis of T1D is necessary compared to intervention at later stages [63].

Table 1compares the properties of MSCs derived from the bone marrow, umbilical cord, and adipose tissue.

Recent research has demonstrated that menstrual blood-derived endometrial stem cells (MenSCs) have therapeutic promise for the treatment of T1D due to their exceptionally high rates of proliferation, noninvasive collection method, and significant immunomodulatory activity. In T1D model mice, MenSC and UC-MSC transplantation resulted in a significant decrease in blood glucose and insulin levels, as well as an improvement in the morphology and function of the liver, kidneys, and spleen [14]. A 2021 study found that MenSCs expressed pancreatic -cell genes such as INSULIN, GLUT-2, and NGN-3 and had a greater capacity to develop into pancreatic cells [64].

Dental pulp-derived mesenchymal stem cells (DP-MSCs) are one of the unique MSCs proposed for the treatment of T1D. DP-MSCs are derived from exfoliated human deciduous teeth and have the properties of being easy to obtain with minimal donor injury. In a study by Mo et al. DP-MSCs revealed the ability to differentiate into pancreatic -cells; nevertheless, before proceeding with larger-scale investigations to firmly establish this approach, it is necessary to devise procedures for optimal -cell differentiation in-vivo [65].

An in-vivo study revealed that conjunctiva-derived mesenchymal stem cells (C-MSCs) efficiently differentiated into pancreatic islet stem cells in 2D cultures and 3D scaffolds under optimal induction conditions. C-MSCs have a strong proliferative capacity, a spindle shape, a high potential for clonogenic differentiation, and are widely available. However, larger in vitro studies are necessary before C-MSCs can be deemed an established treatment for T1D [64].

Table 2 lists all clinical trials that have utilized MSCs in the treatment of T1D and complications related to T1D (Table 2).

Our article relies on a survey of free full-text research journals over the past decade; consequently, it is possible that we have omitted pertinent information from paid full-text as well as research articles published prior to 2010.In addition, the scope of this study is confined to studies in the English language, so we may have overlooked papers published in other languages.

MSCs are postulated to act in T1D and numerous other disorders through diverse mechanisms. Among these are homing and immunomodulation. Our review revealed that MSCs not only effectively reduce fasting blood sugar, C-peptide, and hemoglobin A1c levels but are also capable of treating microvascular complications associated with T1D. However, the specific pathophysiology of T1D diabetes is still unknown, making it difficult to develop novel treatments. To achieve remission of T1D, we must also consider the effects of additional factors on the efficacy of MSCs, including patient-specific variables such as age, body mass index, lifestyle, socioeconomic status, level of activity, diet, autoimmune status, and drug interactions, as well as external factors such as storage conditions, plating density, and culture media. Therefore, it is urgent to conduct larger-scale studies.

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The Role of Mesenchymal Stem Cells in the Treatment of Type 1 Diabetes - Cureus