Category: Paediatrics

Categories : Ageing PaediatricsTags :

Telomere Length May Be Set Early in Life

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Image source: Pixabay

Telomeres, the protective nucleotide end caps of chromosomes which shorten with every cell division, have been found by a new study to undergo great changes in length during the first years of life.

The length of telomeres is important in a number of age-related diseases and is also an important marker of biological age. When telomeres are completely shortened, cells become senescent and unable to divide any further to repair damage.

This study, one of the first to examine telomere length (TL) in childhood, found that the initial setting of TL during prenatal development and in the first years of life may determine one’s TL throughout childhood and potentially even into adulthood or older age. The study also finds that TL decreases most rapidly from birth to age 3, then remaining unchanged into the pre-puberty period, although on some occasions it was seen to lengthen.

Researchers at the Columbia Center for Children’s Environmental Health at Columbia University Mailman School of Public Health led the study, which followed 224 children from birth to age 9. Their findings were published in the journal Psychoneuroendocrinology.

The researchers discovered that a mother’s TL is predictive of newborn TL and tracks with her child’s TL through pre-adolescence. The reasons why some children have telomeres that shorten faster are unknown, though one explanation may be that telomeres are susceptible to environmental pollutants. It is also unknown why some children had telomeres that lengthened across the study period, a phenomenon seen in other studies.

“Given the importance of telomere length in cellular health and aging, it is critical to understand the dynamics of telomeres in childhood,” said senior author Julie Herbstman, PhD, director of CCCEH and associate professor of environmental health science at Columbia Mailman School. “The rapid rate of telomere attrition between birth and age 3 years may render telomeres particularly susceptible to environmental influences during this developmental window, potentially influencing life-long health and longevity.”

Researchers used polymerase chain reaction to measure TL in white blood cells isolated from cord blood and blood collected at ages 3, 5, 7, and 9, from 224 children. In a small group of mothers they also measured maternal TL at delivery.

The researchers said that further research is needed to understand the biological mechanisms behind the variance of TL shortening or lengthening rates in the first years of life, as well as modifiable environmental factors contributing to the shortening speed.

Source: Columbia Mailman School of Health

Categories : Cardiovascular Disease PaediatricsTags :

New Model for Blood Clot Prediction in Children

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Monroe Carell Jr Children’s Hospital at Vanderbilt has launched a study to test out a predictive model for identifying paediatric patients at risk for developing blood clots or venous thromboembolisms.

The study examined the use of advanced predictive analytics to predict the development of blood clots in paediatric patients at risk for them.

“Hospital-associated blood clots are an increasing cause of morbidity in paediatrics,” said the study’s principal investigator, Shannon Walker, MD, clinical fellow of Paediatric Haematology-Oncology at Children’s Hospital.

Though they are rarer events in children than in adults, morbidity and mortality is higher and Dr Walker nevertheless noticed that blood clot development in children was on the rise.

“The reason children get blood clots is very different from adults,” said Dr Walker.
“There was no standardised protocol for preventing clots in paediatric patients. As we noticed that the rate of blood clots was going up and recognised that the adult strategy wasn’t going to work for our patients, we wanted to look at each patient’s individual risk factors and see how we could focus our attention on targeted blood clot prevention.”

The study, which will be published in Pediatrics, describes how the team built and validated a predictive model that can be automated to run within the electronic health record of each patient admitted to the hospital.

The model includes 11 risk factors and was based on an analysis of more than 110 000 admissions to Children’s Hospital and has been validated on more than 44 000 separate admissions.

Currently the team is studying using this model along with targeted intervention in the clinical setting in a trial called “Children’s Likelihood of Thrombosis,” or CLOT.

The prediction model follows this procedure: every child admitted to the hospital has a risk score calculated. The patients are randomised, so in half of the patients, elevated scores are reviewed by a hematologist, and then discussed with each patient’s medical team and family to determine a personalised prevention plan. All patients, regardless of their assigned group, continue to receive the current standard of care.

“We are not utilising a one-size-fits-all plan,” said Walker. “This is an extra level of review allowing for a very personalized recommendation for each patient with an elevated score. Each day the score is updated, so as risk factors change, the scores change accordingly.

“We are, in real-time, assessing the use of this model as a clinical support tool. We saw a clinical opportunity of something we could improve and have moved forward with building the model—to identify high-risk patients and are currently performing the CLOT trial, which will run through the end of the year.”

The Advanced Vanderbilt Artificial Intelligence Laboratory (AVAIL) was instrumental in Walker’s study. Only in its second year, the programme is leading the way in supporting artificial intelligence tools at Vanderbilt University through project incubation and curation, including facilitating clinical trials to assess their effectiveness.

“AVAIL served as a catalyst, in this instance by bringing experts in a complex trial development into proximity so that a great synthesis could happen,” said Warren Sandberg, MD, PhD, who is executive sponsor of AVAIL, along with Kevin Johnson, MD.

“What is unique about this particular project is that we were not only able to predict complications but also able to test the model in a rigorous, pragmatic, randomized, controlled trial to see if it benefits patients,” said Dan Byrne, senior biostatistician for the project and director of artificial intelligence research for AVAIL.

“The future of this kind of work is unlimited,” he said. “We can hopefully use this approach to predict and prevent pressure injuries, sepsis, falls, readmissions or most any complication before they happen. At Vanderbilt, we are raising the bar when it comes to the science of personalised medicine and application of artificial intelligence in medicine in a way that is both ethical and safe.”

Source: Medical Xpress

Categories : Injury & Trauma PaediatricsTags :

Safety Commission Warns on Peloton Treadmill Hazard to Children

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The US Consumer Product Safety Commission (CPSC) has put out a warning for owners of the popular Peloton Tread+ exercise machine following “multiple incidents of small children and a pet being injured beneath the machines.”

The warning comes weeks after Peloton CEO John Foley said a child died in an accident related to the machine. “While we are aware of only a small handful of incidents involving the Tread+ where children have been hurt, each one is devastating to all of us at Peloton, and our hearts go out to the families involved,” he said in a statement.

As a result, the CPSC launched an investigation into the treadmill, one that the commission says remains ongoing. The commission reported that it is aware of 38 other non-fatal safety incidents involving the device.
In the commission’s view, the Peloton Tread+ “poses serious risks to children for abrasions, fractures, and death” resulting from “children becoming entrapped, pinned, and pulled under the rear roller of the product.”

The announcement included a video of a child seemingly pulled underneath the treadmill while playing behind the machine.

The CPSC is advising those with children at home to stop using the Peloton Tread+ treadmill immediately and says that the hazard the machine imposes “cannot be avoided simply by locking the device when not in use.”

“Peloton has not yet agreed to do a recall or a stop sale,” Consumer Product Safety Commission spokesperson Joe Martyak told NPR. He continued, “We hope that will change.”

Generally, product recalls are done on a voluntary basis by companies, in concert with government.

Peloton responded to the CPSC, saying the warning was “inaccurate and misleading.”

“Like all motorized exercise equipment, the Tread+ can pose hazards if the warnings and safety instructions are not followed,” the company said. In response to further questions from NPR about a possible recall, a spokesperson for the company said “a recall has never been warranted.”

The spokesman added that, “The Peloton Tread+ is safe when operated as directed and in accordance with the warnings and safety instructions.”.

Source: NPR

Categories : Diet and Nutrition PaediatricsTags :

Junk Food Impacts Bone Growth in Kids

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Burger and chips. Photo by Jonathan Borba on Unsplash

A new study has found that ultra-processed foods (aka junk food) impacts bone quality, showing how damaging these can be especially in younger children.

The Hebrew University study provides the first comprehensive analysis showing the manner in which such foods impact skeletal development.  

Junk foods go through many processing stages, and contain non-dietary ingredients. They are easily accessible, can be eaten without preparation and fairly cheap, and their increasing presence in diets is contributing to worldwide obesity with its associated metabolic impacts.

Children tend to like junk food. As much as 70% percent of their caloric consumption are estimated to come from ultra-processed foods. While numerous studies have reflected on the overall negative impact of junk food, few have focused on its direct developmental effects on children, particularly young children.

Studying lab rodents with skeletons in post embryonic growth stages, they found that those exposed to ultra-processed foods suffered from stunted growth and compromised bone strength. With histological examination, high levels of cartilage were found in the epiphyseal plates at the end of bones. The RNA genetic profiles of cartilage cells exposed to ultra-processed food also showed signs of impaired boned development.

In order to understand how eating habits might impact bone development, the researchers replicated this kind of food intake for the rodents. “We divided the rodents’ weekly nutritional intake—30% came from a ‘controlled’ diet, 70% from ultra-processed foods,” said Monsonego-Ornan. They found that the rodents experienced bone density moderate damage though there were fewer signs of cartilage buildup in their growth plates. “Our conclusion was that even in reduced amounts, the ultra-processed foods can have a definite negative impact on skeletal growth.”

Children and adolescents eat junk foods in great quantities, with half of American minors eating junk food daily. Monsonego-Ornan added. “When Carlos Monteiro, one of the world’s leading experts on nutrition, said that there is no such thing as a healthy ultra-processed food, he was clearly right. Even if we reduce fats, carbs nitrates and other known harmful substances, these foods still possess their damaging attributes. Every part of the body is prone to this damage and certainly those systems that remain in the critical stages of development.”

Source: Medical Xpress

Journal information: Janna Zaretsky et al. Ultra-processed food targets bone quality via endochondral ossification, Bone Research (2021). DOI: 10.1038/s41413-020-00127-9

Categories : PaediatricsTags :

Parents can Transmit Periodontitis-causing Bacteria to Children

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A study conducted by the University of Campinas (UNICAMP) has found that adults can transmit the bacteria that cause periodontitis to their children, and even remain in the mouth when the children undergo various treatments. 

Periodontitis, which is preceded by gingivitis, is a bacterially caused inflammation of the periodontium, the tissue supporting the teeth. It is characterised by swollen and bleeding gums and halitosis, and can result in loss of teeth in severe cases.

Should the microorganisms responsible for the disease enter the bloodstream, they may trigger other kinds of inflammation in the body. The disease can be treated by cleaning the pockets around the teeth by a dentist or dental hygienist and administration of anti-inflammatory drugs or antibiotics.

“The parents’ oral microbiome is a determinant of the subgingival microbial colonization of their children,” the article’s wrote in their conclusion, adding that “dysbiotic microbiota acquired by children of periodontitis patients at an early age are resilient to shift and the community structure is maintained even after controlling the hygiene status”.

According to the first author of the article, dental surgeon Mabelle de Freitas Monteiro, she and her group have been researching periodontitis for ten years, and have observed both parents with the disease and their children, and noted the impact on their health.

“If the findings are applied to day-to-day dental practice, the study can be said to help design more direct approaches. Knowing that periodontal disease may affect the patient’s family is an incentive to use preventive treatment, seek early diagnosis and mitigate complications,” said Monteiro, who was supported by FAPESP via two projects.

The principal investigator for both of these projects was Renato Corrêa Viana Casarin, a professor at UNICAMP’s Piracicaba Dental School (FOP), who is the last author of the article .

In Prof Casarin’s view, parents’s care of their children’s dental hygiene should start when they are still infants.

“This pioneering study compares parents with and without periodontitis,” said Prof Casarin. “In children of the former, we found subgingival bacterial colonization at a very early age. However, ‘inheriting’ the problem doesn’t mean a child is fated to develop the disease in adulthood. Hence the importance of keeping an eye open for the smallest signs and seeking specialized help.”

According to the latest national dental epidemiological survey from 2010, 18% of children aged 12 had never been to the dentist and 11.7% had experienced bleeding of the gums. Of those in the 15-19 age group, 13.6% had never visited a dental clinic. The planned 2020 survey was postponed due to COVID. According to the São Paulo State Department of Health’s  latest oral health survey in 2019 revealed that 50.5% of adults aged 35-44 complained of toothache, bleeding gums and periodontitis.

In the FOP-UNICAMP study led by Casarin and Monteiro, the team colleclected samples of subgingival biofilm and plaque from 18 adults with a history of generalised aggressive (grade C) periodontitis, their children aged 6-12, and 18 orally healthy adults.

As well as a clinical analysis, the samples were also subjected to a microbiological analysis and genetic sequencing by Ohio State University researchers.

“Children of periodontitis parents were preferentially colonized by Filifactor alocis, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Streptococcus parasanguinis, Fusobacterium nucleatum and several species belonging to the genus Selenomonas even in the absence of periodontitis,” the article states. “These pathogens also emerged as robust discriminators of the microbial signatures of children of parents with periodontitis.”

Prof Casarin told Agência FAPESP that even with bacterial plaque control and vigorous brushing, children of people with the disease still had the bacteria in their mouths, whereas the effects of dental hygiene and prophylaxis were more significant in the children of healthy subjects.

“Because the parents had periodontitis, their children assumed this community with disease characteristics. They carried the bacterial information into their adult lives,” he said, adding that the analysis of bacterial colonisation indicated the transmission was more likely from the mother. The research group’s next step is working with pregnant women to prevent bacterial colonisation of their children’s mouths.

“We’ll treat the mothers during pregnancy, before the babies are born, and try to find out if it’s possible to prevent bacterial colonization from occurring,” Casarin said, adding that studies with patients will only go ahead when the pandemic is under control.

Source: News-Medical.Net

Journal information: Monteiro, M. F., et al. (2021) Parents with periodontitis impact the subgingival colonization of their offspring. Scientific Reports. doi.org/10.1038/s41598-020-80372-4.

Categories : Cancer General Interest PaediatricsTags :

Donated Afro Hair Wigs Now Possible Thanks to UK Girl

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A silhouetted woman with afro hair reading a book by a window. Photo by Thought Catalog from Pexels

A British girl who was told her afro hair was too delicate to donate for wig-making prompted a new wig-making approach to use it, BBC News reports.

When eleven year old Carly Gorton wanted to donate her afro hair to the Little Princess Trust charity, which makes natural hair wigs for children who have lost theirs from cancer treatment and other causes, she was initially frustrated as the charity said the hair was too delicate. Undeterred, Carly had urged the charity to rethink, which it did.

Following research and a trial to make them possible, the charity described the new wigs as a “historic breakthrough”.

“It’s really beautiful,” said Carly, of one of the new wigs.

A BMJ study showed that wigs positively impact psychological wellbeing for people with alopecia, attributed to increasing their confidence of going out in public and the perception of fewer comments about hair loss.

At a special school assembly, Carly’s mother Anna Mudeka then cut her daughter’s hair and it was donated for use in the first new wigs to be worn by other children.

Phil Brace, The Little Princess Trust’s chief executive, said Carly’s “determination” to donate her hair had pushed them to find a solution.

The charity worked with the 120-year-old London company Raoul to develop a wefting method to weave and tie the donated locks.

Carly’s mother, Anna Mudeka, said: “History has been made and we are so proud of Carly.

“Through her sheer determination and everyone pulling together to hear her voice, children of black and mixed heritage can now donate their hair to the Little Princess Trust.”

Ms Mudeka, of Southburgh, added that children needing wigs through illness could now receive a wig “true to their heritage”.

Carly and her mother’s campaign had created a “fundamental change in wig manufacturing”, said Mr Brace. “The commitment and work that has gone on has shown just what is possible when groups of people get together and bring different skills to find a solution.”

Source: BBC News

Categories : PaediatricsTags :

New ADHD Drug Gets FDA Approval for Children

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US regulators have approved the first new ADHD drug for children in over a decade.

The Food and Drug Administration last week approved  viloxazine (Qelbree) for the treatment of attention deficit hyperactivity disorder in children ages 6 to 17. It was developed by  Supernus Pharmaceuticals. The drug’s price was undisclosed but is likely to be higher than the generic ADHD pills.

In Europe, viloxazine was sold as an antidepressant for several decades, but never received FDA approval. It was discontinued nearly two decades ago, due to competition from popular pills like Zoloft and Prozac.

ADHD affects about 6 million American children and adolescents. For many, problems include trouble paying attention and completing tasks, fidgeting and impulsiveness.  

Earlier ADHD treatments like Ritalin, nearly all of which contain the stimulants amphetamine or methylphenidate, which create the potential for abuse. Viloxazine however is not a stimulant or a controlled substance. It carries a warning of potential for suicidal thoughts and behaviour, which occurred in fewer than 1% of volunteers in studies of the drug.

Qelbree could be an option for children with substance use disorders, who do not cope well with stimulant side effects or who need more therapy, said Dr David W. Goodman, director of Suburban Psychiatric Associates near Baltimore and an assistant professor of psychiatry at Johns Hopkins School of Medicine.

Goodman said that long-acting stimulants prescribed to ADHD patients currently are harder to abuse to get a high than the older fast-acting versions.

In a late-stage study, 477 children ages 6 to 11 took viloxazine for six weeks. Compared to placebo, Inattention and hyperactivity symptoms were reduced by about 50%. Symptom reduction was seen within a week in some participants. Its common side effects include sleepiness, lethargy, decreased appetite and headache.

Supernus is in late-stage testing for adults with ADHD, who represent a small but growing market as adult treatment of the condition expands.

Source: Medical Xpress

Categories : Cancer PaediatricsTags :

Blood Mutation Explains High Leukaemia Rates in Children with Down’s

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According to a new study by researchers at the Linda Crnic Institute for Down Syndrome, the reason that children with Down syndrome have a drastically elevated risk of leukaemia is due to a more prevalent condition increasing blood stem cell mutation.

Children with Down syndrome are 20-times more likely to develop acute lymphocytic leukaemia (ALL) and 150-times more likely to develop acute myeloid leukaemia (AML) compared to their typical peers. The researchers found that the reason for this is that they are more likely to present with clonal haematopoiesis (CH), a process in which a blood stem cell acquires a genetic mutation that promotes replication.  

The findings add to a growing body of evidence linking immune dysregulation to a very different disease spectrum, whereby people with Down syndrome are highly predisposed to certain diseases such as leukaemia and autoimmune disorders, while being highly protected from others, such as solid tumours.

“We found a higher-than expected rate of CH in individuals with Down syndrome between the age of one to 20 years old,” said study author Dr Alexander Liggett, who as a doctoral candidate led the study in the lab of Dr James DeGregori, Professor of Biochemistry and Molecular Genetics. “It is a surprising finding, as the phenomenon is typically only observed in elderly people.”

The researchers used an advanced sequencing technique that they had developed, called FERMI, to blood samples from the Crnic Institute Human Trisome Project Biobank. Mutations were more likely to be detected in Down’s syndrome and also more likely to be oncogenic. In elderly people, oncogenic mutations are commonly found in the genes DNMT3A, TET2, ASXL1, TP53, and JAK2. In people with Down’s syndrome, oncogenic CH was found to be dominated by mutations of the TET2 gene.

“Given the increased risk of leukaemia that accompanies clonal expansion of blood cells carrying oncogenic mutations, these expansions may become an important biomarker of cancer risk in the future,” said Dr Liggett.

The study also found that CH in Down syndrome is associated with immune dysregulation biosignatures linked to diseases co-occurring with Down’s syndrome, including thyroiditis, Alzheimer’s disease, and leukaemia. This discovery opens new avenues in understanding the way CH impacts an array of health outcomes in Down syndrome and how to potentially counteract its effects.

“This is truly transformative. This team has identified a new trait of Down syndrome that has strong implications for understanding the appearance of comorbidities more common in this population, such as leukaemia and premature ageing,” said Dr. Joaquin Espinosa, Executive Director of the Crnic Institute. “The next step is to define the long-term impacts of this precocious clonal hematopoiesis and how to prevent its harmful effects.”

Source: News-Medical.Net

Journal information: Liggett, L.A., et al. (2021) Precocious clonal hematopoiesis in Down syndrome is accompanied by immune dysregulation. Gut. doi.org/10.1182/bloodadvances.2020003858.

Categories : Neurology PaediatricsTags :

Boy’s Brain Rewires After Stroke as a Newborn

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Photo by cottonbro from Pexels

Researchers have reported the case of a boy whose brain was able to rewire after a severe stroke that damaged much of his brain.

In the seventh grade, 13-year old Daniel Carr amazed his baseball coach with his ability to throw with his left hand, saying that it was the fastest he’d ever seen. However, he was unable to properly catch with his right hand.

Hearing this from the coach, Kellie Carr, Daniel’s mother, realised that his son had a number of quirks, such as favouring his left side when he was an infant, and his left-handedness emerged well before the normal age of two or three. However, she was unable to get any explanation for this until she met Nico Dosenbach, MD, PhD, who informed her that her son had had a stroke when he was a newborn.

MRI scans revealed large, bilateral voids in Daniel’s brain, but incredibly, he had no cognitive, behavioural or motor problems other than a lack of strength and dexterity in his right arm.
“The extent of Daniel’s injuries may be on the edge of what’s compatible with life,” Dosenbach said.

Dainel’s remarkable recovery can be explained by his young age at the time the stroke.

“The brain can compensate more quickly and completely for strokes sustained in early childhood,” he said. “By contrast, large strokes in adults often cause death or severe functional impairment with little chance of recovery. However, the mechanics behind this are only beginning to be understood.”

More MRI scans were done on Daniel’s brain to determine its structure and pathology. Dosenbach and Laumann conducted high-resolution functional MRI scans to understand how Daniel’s brain had reorganised itself.
With his mother’s consent, Daniel was further tested over a period of six years, including batteries of neurological tests, and more scans done. Timothy Laumann, MD, PhD, now a fourth-year psychiatry resident at Barnes-Jewish Hospital, had the expertise to analyse the data.

Looking at his medical records, the physician-scientists noted that he had an infection as a newborn, and was hospitalised with an IV drip. However, none of the physicians had suspected a stroke, which happens to one in every 4000 newborns. Daniel was sent home after a week, the doctors having suspected a viral infection.

“The risk of having a pediatric stroke greatly increases with a medical problem, especially an infection during the newborn period,” Dosenbach said. “However, usually there are more obvious signs that a stroke occurred. I can understand how no one suspected it.”

The researchers compared the images of Daniel’s brain to others of young adults, as well as Dosenbach’s own brain, which he had imaged and studied extensively.

“Part of Daniel’s brain structure is gone,” Laumann explained, referring to their analysis of the MRI data. “He’s missing almost a quarter of his cortex.”

The dead tissue was replaced by pockets of cerebrospinal fluid, which acts as a shock absorber, as well as delivering nutrients and removing waste. The surviving neurons formed interconnected islands that restored cognitive and motor functions, and neighbourhoods of healthy tissue were again reconnected.

“Our findings illustrate the brain’s tenacity at reorganizing and recovering functions damaged by a massive stroke affecting both sides of his brain,” Dosenbach said. “Future studies of functional remapping relative to tissue loss may provide additional insights. Our results raise the possibility that variability in outcomes may depend on specific features unique to an individual’s brain.”

Despite the extensive damage, Daniel completed tertiary education and now works as a diesel mechanic.

“His stroke still shocks me,” Kellie Carr said. “How could I have not known? But looking back, maybe it was better that way. I might have babied Daniel and been afraid to let him be a regular kid. Maybe the best thing for him was living normally.”

Daniel agreed: “I think about my right hand daily because I have to constantly think five steps ahead to figure out how to compensate for not being able to use it properly, like I did with the baseball glove. But the last thing I want is for people to act like something is wrong with me. I’m fine.”

Source: Medical Xpress

Journal information: Timothy O Laumann et al. Brain network reorganisation in an adolescent after bilateral perinatal strokes, The Lancet Neurology (2021). DOI: 10.1016/S1474-4422(21)00062-4

Categories : Implants and Prostheses PaediatricsTags :

Lab-made Heart Valves That Can Grow With The Recipient

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In a new study, lab-made heart valves were shown to grow along with their recipient when implanted into lambs for a year, making a new alternative possible for thousands of paediatric patients who need replacement heart valves. 

Researchers from the University of Minnesota Twin Cities’ College of Science and Engineering and the Medical School published the results in Science Translational Medicine. The production procedure for the valves has also been patented and licensed to the University of Minnesota startup company Vascudyne, Inc.

Compared to currently used animal-derived valves, these new valves also showed reduced calcification and improved blood flow when tested in the same growing lamb model. Current solutions for children involve prosthetic valves, but these calcify over time and cannot grow with the patient. This requires up to five open-heart surgeries to replace them as the children grow towards adulthood, involving considerable risk and expense, as well as demanding lifelong anticoagulation therapy.

“This is a huge step forward in paediatric heart research,” commented senior researcher Robert Tranquillo, a University of Minnesota professor in the Departments of Biomedical Engineering and the Department of Chemical Engineering and Materials Science. “This is the first demonstration that a valve implanted into a large animal model, in our case a lamb, can grow with the animal into adulthood. We have a way to go yet, but this puts us much farther down the path to future clinical trials in children. We are excited and optimistic about the possibility of this actually becoming a reality in years to come.”

Using a combination of tissue engineering and regenerative medicine, they were able to grow the heart valves. Implementing a tissue engineering technique they had previously developed, they grew tube-like structures out of skin cells. This involved combining the skin cells in fibrin, and providing nutrients in a bioreactor. After washing the skin cells out with detergent, the researchers were left with a collageneous matrix which would not provoke an immune response when implanted. They then sewed and trimmed three of these tubes together to make a 19mm diameter heart valve-like structure.

“After these initial steps, it looked like a heart valve, but the question then became if it could work like a heart valve and if it could grow,” Tranquillo said. “Our findings confirmed both.”

The valves grew from 19mm to 25mm over a year, and showed little of the calcification or clotting associated with prosthetic valves, while performing better than animal-derived valves.”We knew from previous studies that the engineered tubes have the capacity to regenerate and grow in a growing lamb model, but the biggest challenge was how to maintain leaflet function in a growing valved conduit that goes through 40 million cycles in a year,” said lead researcher Zeeshan Syedain, a University of Minnesota senior research associate in Tranquillo’s lab. “When we saw how well the valves functioned for an entire year from young lamb to adult sheep, it was very exciting.”

The next steps are to implant the valve into the right ventricle of the heart to see how it performs, and apply for FDA approval to proceed to human trials. 

Source: Medical Xpress

Journal information: Zeeshan H. Syedain et al, Pediatric tri-tube valved conduits made from fibroblast-produced extracellular matrix evaluated over 52 weeks in growing lambs, Science Translational Medicine (2021). DOI: 10.1126/scitranslmed.abb7225