Researchers at the Wake Forest Institute for Regenerative Medicine (WFIRM) have helped rabbits have normal pregnancies and live births after their injured uteri were repaired using a method of tissue engineering with their own cells. The approach may have implications for women affected by uterine infertility.
While transplants from live or deceased donors have enabled live births in humans, a lack of donor organs and the need for immunosuppressive drugs to support the transplanted uterus limit its use. Bioengineering had been shown to repair small uterine defects in rodents, but live birth in these or larger animals has not yet been achieved.
“The study shows that engineered uterine tissue is able to support normal pregnancies, and fetal development was normal, with offspring size and weight being comparable to those from a normal uterus,” said Anthony Atala, MD, principal investigator and WFIRM director. “With further development, this approach may provide a pathway to pregnancy for women with an abnormal uterus.”
Scientists implanted biodegradable scaffolds—some with the rabbits’ own uterine cells inserted and some without—into the damaged uteri of 78 rabbits. The uteri were examined at one, three and six months. The authors found the scaffolds had degraded three months after implantation, and by six months they observed no obvious differences between the engineered and native tissues.
Four of the 10 rabbits that received scaffolds seeded with uterine cells had normal pregnancies to term, but none of the 10 rabbits that received unseeded scaffolds did.
The study was published in Nature Biotechnology, and earned media coverage from the BBC’s Science Focus Magazine.
“Mindfulness-based stress reduction is a mind-body treatment that teaches moment-by-moment awareness through mindfulness meditation and yoga,” said Rebecca Erwin Wells, MD, MPH, associate professor of neurology and founder and director of the Comprehensive Headache Program at Wake Forest Baptist. “Mindfulness can also teach new ways to respond to stress, a commonly reported migraine trigger.”
According to an article published by JAMA Internal Medicine, researchers studied whether MBSR improved migraine outcomes, pain perception and measures of emotional well-being compared to headache education. In the study, 89 adults with a history of migraine were randomly assigned to either the MBSR group or headache education group with training or instruction delivered in eight weekly two-hour sessions.
The MBSR group followed a standardized curriculum of mindfulness meditation and yoga. Participants also received electronic audio files for home practice and were encouraged to practice at home 30 minutes a day. The headache education group received instruction on headaches, pathophysiology, triggers, stress and treatment approaches.
Participants in both groups reported fewer days with migraine. However, MBSR also lessened disability and improved quality of life, depression scores and other measures reflecting emotional well-being, with effects seen out to 36 weeks.
“At a time when opioids are still being used for migraine, finding safe non-drug options with long-term benefit has significant implications,” Wells said.
Such studies are critical to understanding the effects of low gravity, radiation, confined spaces, and more as NASA sends astronauts deep into space for extended missions to the moon, Mars and beyond.
“What our study discovered was that the powerhouse machinery of the cell that is largely responsible for making energy, called the mitochondria, is dysfunctional in cells, mice and humans during spaceflight,” Willey said. “Dysfunction of the mitochondria occurs in many health problems on Earth, such as certain cancers, heart diseases and others. Our research efforts aimed at protecting human health in space may also apply to helping promote good health here on Earth.”
“Our data shows that nicotine exposure creates an environment in the lungs that is ripe for metastatic growth,” said Kounosuke Watabe, PhD, lead author of the study and professor of cancer biology. The study was published in January in the online edition of Nature Communications.
This environment, called a pre-metastatic niche, attracts pro-tumor neutrophils, a type of immune cells. The pre-metastatic niche releases a protein called STAT3-activated lipocalin 2 (LCN2) from the neutrophils to induce metastatic growth. For the study, Watabe’s team first studied 1,077 breast cancer patients and found that current smokers or former smokers have a higher incidence of lung metastasis compared to patients who never smoked.
Breast cancer is the second most common cancer among women in the United States, and cigarette smoking is associated with a higher incidence of breast cancer spread, or metastasis, lowering the survival rate by 33% at diagnosis.
In research published last year in the Journal of Experimental Medicine, Watabe’s team also found that nicotine promotes the spread of lung cancer cells into the brain. “Based on our findings, we don’t think that nicotine replacement products are the safest way for people with lung cancer to stop smoking,” he said.
This cartilage, known as fibrocartilage, helps connect tendons or ligaments or bones and is primarily found in the meniscus in the knee. The meniscus is the tough, rubbery cartilage that acts as a shock absorber in the knee joint. Degeneration of the meniscus tissue affects millions of patients, and arthroscopic partial meniscectomy is one of the most common orthopedic operations performed. Besides surgery, there is a lack of available treatment options.
In this latest proof-of-concept strategy, the scientists were able to 3D bioprint a hybrid tissue construct for cartilage regeneration by printing two specialized bioinks – hydrogels that contain the cells – together to create a new formulation that provides a cell-friendly microenvironment and structural integrity. This work is done with the Integrated Tissue and Organ Printing System, a 3D bioprinter that was developed by WFIRM researchers over a 14-year period. The system deposits both biodegradable, plastic-like materials to form the tissue “shape” and bioinks that contain the cells to build new tissues and organs.
“In this study, we have been able to produce a highly elastic hybrid construct for advanced fibrocartilaginous regeneration,” said Sang Jin Lee, PhD, associate professor at WFIRM and author of the paper published in fall 2020 by Chemistry of Materials journal. “The results demonstrate that this bioprinted construct offers a versatile and promising alternative for the production of this type of tissue.”
While transplants from live or deceased donors have enabled live births in humans, a lack of donor organs and the need for immunosuppressive drugs to support the transplanted uterus limit its use. Bioengineering had been shown to repair small uterine defects in rodents, but live birth in these or larger animals has not yet been achieved.
“The study shows that engineered uterine tissue is able to support normal pregnancies, and fetal development was normal, with offspring size and weight being comparable to those from a normal uterus,” said Anthony Atala, MD, principal investigator and WFIRM director. “With further development, this approach may provide a pathway to pregnancy for women with an abnormal uterus.”
Scientists implanted biodegradable scaffolds—some with the rabbits’ own uterine cells inserted and some without—into the damaged uteri of 78 rabbits. The uteri were examined at one, three and six months. The authors found the scaffolds had degraded three months after implantation, and by six months they observed no obvious differences between the engineered and native tissues.
Four of the 10 rabbits that received scaffolds seeded with uterine cells had normal pregnancies to term, but none of the 10 rabbits that received unseeded scaffolds did.
The study was published in Nature Biotechnology, and earned media coverage from the BBC’s Science Focus Magazine.
Mindfulness Meditation May Decrease Impact of Migraine
Researchers leading a clinical trial at Wake Forest Baptist Health showed that mindfulness-based stress reduction (MBSR) may provide benefit to people with migraines, the second leading cause of disability worldwide.“Mindfulness-based stress reduction is a mind-body treatment that teaches moment-by-moment awareness through mindfulness meditation and yoga,” said Rebecca Erwin Wells, MD, MPH, associate professor of neurology and founder and director of the Comprehensive Headache Program at Wake Forest Baptist. “Mindfulness can also teach new ways to respond to stress, a commonly reported migraine trigger.”
According to an article published by JAMA Internal Medicine, researchers studied whether MBSR improved migraine outcomes, pain perception and measures of emotional well-being compared to headache education. In the study, 89 adults with a history of migraine were randomly assigned to either the MBSR group or headache education group with training or instruction delivered in eight weekly two-hour sessions.
The MBSR group followed a standardized curriculum of mindfulness meditation and yoga. Participants also received electronic audio files for home practice and were encouraged to practice at home 30 minutes a day. The headache education group received instruction on headaches, pathophysiology, triggers, stress and treatment approaches.
Participants in both groups reported fewer days with migraine. However, MBSR also lessened disability and improved quality of life, depression scores and other measures reflecting emotional well-being, with effects seen out to 36 weeks.
“At a time when opioids are still being used for migraine, finding safe non-drug options with long-term benefit has significant implications,” Wells said.
Wake Forest Baptist Scientist Publishes Finding from NASA’s Twins Study
Research conducted by Jeffrey Willey, PhD, associate professor of radiation oncology, on aspects of the effects of spaceflight on the human body was published in November in the journal Cell. His research included data from NASA’s Twins Study and from other missions that collected experimental research on the International Space Station including samples from 59 astronauts, and from both cell- and rodent-based studies.Such studies are critical to understanding the effects of low gravity, radiation, confined spaces, and more as NASA sends astronauts deep into space for extended missions to the moon, Mars and beyond.
“What our study discovered was that the powerhouse machinery of the cell that is largely responsible for making energy, called the mitochondria, is dysfunctional in cells, mice and humans during spaceflight,” Willey said. “Dysfunction of the mitochondria occurs in many health problems on Earth, such as certain cancers, heart diseases and others. Our research efforts aimed at protecting human health in space may also apply to helping promote good health here on Earth.”
Scientists Discover Link Between Nicotine and Breast Cancer Metastasis
While cigarette smoking’s link to cancer is well-known, the role of nicotine, a non-carcinogenic chemical found in tobacco, in breast-to-lung metastasis is an area where more research is needed. Now, scientists at Wake Forest School of Medicine have found that nicotine promotes the spread of breast cancer cells into the lungs.“Our data shows that nicotine exposure creates an environment in the lungs that is ripe for metastatic growth,” said Kounosuke Watabe, PhD, lead author of the study and professor of cancer biology. The study was published in January in the online edition of Nature Communications.
This environment, called a pre-metastatic niche, attracts pro-tumor neutrophils, a type of immune cells. The pre-metastatic niche releases a protein called STAT3-activated lipocalin 2 (LCN2) from the neutrophils to induce metastatic growth. For the study, Watabe’s team first studied 1,077 breast cancer patients and found that current smokers or former smokers have a higher incidence of lung metastasis compared to patients who never smoked.
Breast cancer is the second most common cancer among women in the United States, and cigarette smoking is associated with a higher incidence of breast cancer spread, or metastasis, lowering the survival rate by 33% at diagnosis.
In research published last year in the Journal of Experimental Medicine, Watabe’s team also found that nicotine promotes the spread of lung cancer cells into the brain. “Based on our findings, we don’t think that nicotine replacement products are the safest way for people with lung cancer to stop smoking,” he said.
Scientists Create Hybrid Tissue Construct for Cartilage Regeneration
Wake Forest Institute for Regenerative Medicine scientists (WFIRM) have developed a method to bioprint a type of cartilage that could someday help restore knee function damaged by arthritis or injury.This cartilage, known as fibrocartilage, helps connect tendons or ligaments or bones and is primarily found in the meniscus in the knee. The meniscus is the tough, rubbery cartilage that acts as a shock absorber in the knee joint. Degeneration of the meniscus tissue affects millions of patients, and arthroscopic partial meniscectomy is one of the most common orthopedic operations performed. Besides surgery, there is a lack of available treatment options.
In this latest proof-of-concept strategy, the scientists were able to 3D bioprint a hybrid tissue construct for cartilage regeneration by printing two specialized bioinks – hydrogels that contain the cells – together to create a new formulation that provides a cell-friendly microenvironment and structural integrity. This work is done with the Integrated Tissue and Organ Printing System, a 3D bioprinter that was developed by WFIRM researchers over a 14-year period. The system deposits both biodegradable, plastic-like materials to form the tissue “shape” and bioinks that contain the cells to build new tissues and organs.
“In this study, we have been able to produce a highly elastic hybrid construct for advanced fibrocartilaginous regeneration,” said Sang Jin Lee, PhD, associate professor at WFIRM and author of the paper published in fall 2020 by Chemistry of Materials journal. “The results demonstrate that this bioprinted construct offers a versatile and promising alternative for the production of this type of tissue.”