Researchers Optimize Lung Stem Cell Engineering ProcessDecember 31, 1969
Researchers Optimize Lung Stem Cell Engineering Process
(Boston) – The Center for Regenerative Medicine (CReM) at Boston University and Boston Medical Center has engineered two new categories of lung epithelial cells in vitro using pluripotent stem cells. Published in Stem Cell Reports, CReM researchers detailed their use of single cell RNA sequencing, a state-of-the-art technique they employed to generate the most comprehensive profile to date of air sack-like (alveolospheres) and airway-like (bronchospheres) cells derived from pluripotent stem cells. These profiles are new components associated with the Center’s Open Source stem cell repository and can be used to create lung tissue in vitro enabling the testing of new drug treatments for a variety of lung diseases.
Diseases affecting the lung, including emphysema, cystic fibrosis, acute respiratory distress syndrome and pulmonary fibrosis, cause considerable morbidity and mortality in the US. However, there are not many treatment options available for those diseases, in part due to the limited availability of human lung cells for research.
Creating human lung epithelial cells in the lab has been a challenge, and lineage-specific reporters, which indicate each cell’s specific type, are key to understanding lung epithelial stem cell development. In this study, the researchers used both murine and human pluripotent stem cell lines with airway secretory lineage reporters, which enables their tracking, purification and profiling. Mapping the expression profiles of all genes one cell at a time revealed unexpected heterogeneity in the stem cell-derived lung cells, and the research team at the CReM used this information to improve the airway cells engineered in the lab.
“With our collaborators, we were able to identify factors that we can use to more optimally generate patient-derived lung cells in vitro,” said Katie McCauley, PhD, a post-doctoral fellow in the CReM and the study’s first author.
CReM’s pioneering research using induced pluripotent stem cells (iPSCs), which self-renew indefinitely as undifferentiated cells that become specific adult cell types, has helped create an inexhaustible source of disease- or patient-specific stem cells. Researchers use these cells to construct disease models in a lab and test potential treatments for a variety of diseases affecting the lungs. In 2014, the National Institutes of Health helped to fund the first of its kind lung stem cell repository, which provides researchers open (free) access to the different types of induced pluripotent lung cells to use in their laboratories.
“These findings help us stay true to our mission of Open Source sharing of datasets, cells, and protocols with our colleagues who are dedicated to applying these tools to one day help patients,” said senior author Darrell Kotton, MD, the David C. Seldin Professor of Medicine at BU School of Medicine and Director of the CReM of Boston University and Boston Medical Center. “The global research community now has access to this information, which they can use to better understand these newly engineered cells and more quickly develop disease-specific cell line models that can be used to test new therapies and treatments for diseases.”
This research was done in collaboration with the University of Pennsylvania, Cedars-Sinai Hospital, and Vanderbilt University, and was funded by the National Institutes of Health.
Patients with Medicaid Have Limited Access to Physical Therapy in Massachusetts after ACL SurgeryDecember 31, 1969
Patients with Medicaid Have Limited Access to Physical Therapy in Massachusetts after ACL Surgery
(Boston) - Patients with Medicaid in Massachusetts have limited access to reimbursable physical therapy (PT) after anterior cruciate ligament (ACL) reconstruction surgery, according to a new study. Researchers at Boston Medical Center found that only slightly more than half of PT clinics in the metropolitan Boston area accept Medicaid, and patients with Medicaid insurance have to wait longer for their initial PT appointments compared to those with private insurance. The authors note the importance of providers working with their patients with Medicaid earlier on in the process to establish a postoperative treatment plan to avoid PT treatment delays.
ACL reconstructions are among the most common sports medicine procedures performed in the US each year, with previous studies estimating that 175,000 are performed annually. That number continues to increase, and setting up formal PT sessions right after surgery helps ensure both proper and quality postoperative rehabilitative care is provided in order to improve function while minimizing complications for these patients.
“In our orthopaedic sports medicine clinic, we’ve heard firsthand from patients with Medicaid that it is increasingly difficult for them to find PT practices that accept their insurance,” said Xinning Li, MD, orthopaedic surgeon specializing in sports medicine and shoulder surgery at Boston Medical Center. “This results in Medicaid patients returning for follow up or postoperative visits without having been able to do the prescribed PT treatment and exercises, which leads to delayed functional improvement and stiffness.”
Locations in greater Boston offering PT services were identified by using Google, Yelp, and Yellow Pages internet services – the same search methods that a real patient might use. Of the 139 practices that researchers made contact with, 96.4 percent of practices took private insurance, while only 51.8 percent accepted Medicaid. Among locations that did not accept Medicaid, less than one third were able to refer patients to a location that would accept Medicaid. “No contract” was the most common reason why Medicaid was not accepted (39.4 percent).
Average time to first appointment also differed significantly for privately insured patients and those with Medicaid – 5.8 days verses 8.4. There was no difference between PT practice locations (town median income or poverty level) and insurance type accepted. Patients residing in lower income areas did not have improved access to PT facilities that would take Medicaid, and they may have to travel farther distances with limited resources to find a PT practice that would accept their insurance.
“The faster, easier access to PT for privately insured individuals could be due to the difference in reimbursement rates between the two insurances, or because the physical therapy centers have limited spots available for patients with Medicaid,” said Li, who is also an associate professor of sports medicine and shoulder surgery at Boston University School of Medicine.
Li suggests that providers counsel Medicaid patients on how to establish a postoperative rehabilitation plan when initially preparing a patient for ACL surgery to start the discussion about this anticipated barrier to recovery. With adequate planning by the surgeon and/or hospital, the obstacle of securing a postoperative PT appointment that accepts Medicaid is surmountable. In addition, establishing a home-based exercise program with Medicaid patients that have poor access to PT services may also help improve their outcomes.
“Our study shows a gap for some of our most vulnerable patients, and providers and insurers need to collaborate in order to address these barriers so that patients can more readily access the treatment and services necessary for their recovery,” said Li.
This study is published online in The Orthopaedic Journal of Sports Medicine.
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Neonatal Abstinence Syndrome Review: Additional Research Needed to Develop Optimal Assessment, Treatment StandardsDecember 31, 1969
Neonatal Abstinence Syndrome Review: Additional Research Needed to Develop Optimal Assessment, Treatment Standards
(Boston) – A recent JAMA review article stresses that more clinical studies on neonatal abstinence syndrome (NAS) are needed in order to develop and implement optimal assessment, diagnosis and treatment guidelines. Researchers from Boston Medical Center’s (BMC) Grayken Center for Addiction led a review of published studies on NAS assessment tools, and pharmacologic and nonpharmacologic treatment approaches. There has been a particular interest in utilizing approaches that don’t include medication as a first-line treatment, such as breastfeeding and rooming-in, and several small analyses of this work have yielded positive short-term results. However, the authors note, the data is insufficient given several factors, including small sample sizes and single-site studies. They conclude that future research must focus beyond the short-term outcomes by evaluating how different treatments for NAS impact the child’s development and well-being in the long term.
The incidence of NAS continues to rise, now estimated that 20 out of 1,000 infants are born exposed to opioids in utero. Signs of withdrawal from NAS usually appear two to three days after birth and can include irritability, trouble eating and sleeping, diarrhea, muscle rigidity, and difficulty soothing. Providers assess the infant using a standardized assessment tool and determine the need for medication treatment accordingly. The medications used to treat withdrawal symptoms in infants with NAS include morphine, methadone, and buprenorphine.
Lead author Elisha Wachman, MD, a neonatologist at BMC and researcher with the Grayken Center, and her colleagues looked at PubMed, Web of Science, and the Cumulative Index to Nursing and Allied Health Literature for peer-reviewed studies about NAS published between July 1, 2007 and Dec. 31, 2017 that focused on NAS diagnosis and treatment. There were 53 articles included in the review, which were a combination of randomized control trials (RCT), cohort studies, case series and one cross-sectional study. The specific aspects of NAS assessment, diagnosis and treatment included: using nonpharmacologic methods to treat withdrawal symptoms, including rooming-in and breastfeeding; using pharmacologic methods to treat withdrawal symptoms, including morphine, buprenorphine or methadone; and how the mother’s medication treatment for addiction during pregnancy, including buprenorphine or methadone, impacted the severity of the infant’s withdrawal during the hospitalization.
The authors note that the most clinically significant advances in NAS treatment approaches relate to nonpharmacologic interventions, such as parental rooming in and breastfeeding. While initial data shows that using these approaches decreases the need for opioid replacement medication and shortens hospitalizations, larger, prospective multi-site clinical trials are necessary in order to identify optimal treatment approaches without medication.
“The emphasis on truly using non-pharmacologic care as first-line treatment for NAS is a relatively new approach, and while there are several studies showing positive results for the infant as well as the health system, additional research is needed to determine which specific aspects of the non-pharmacologic care bundle are producing the best results both in the short term and the long term,” said Wachman, who is assistant professor of pediatrics at Boston University School of Medicine.
The studies about pharmacologic treatment of NAS examined how different medications, including buprenorphine, morphine and methadone, affected withdrawal symptoms. There are several different medication regimens used to treat NAS, but there is insufficient data to indicate one is more beneficial than others. There are currently clinical trials taking place to compare these medications to determine the best approach. Future research should also focus on whether these medications could safely be weaned in an outpatient setting.
The authors also reviewed data from studies looking at the impact of medication for the treatment of opioid use disorder taken by pregnant mothers on the severity of NAS withdrawal symptoms in the infant. Their findings were that buprenorphine is associated with improved hospitalization outcomes in comparison to methadone, however with unclear impact on long-term outcomes. Additional research is necessary to determine which medication would produce optimal results for both the mother in terms of her recovery and the infant.
“It is important to look beyond the initial hospitalization outcomes for infants with NAS and their mothers in order to determine standards of care that yield the best possible short and long-term outcomes for these patients,” said Wachman. “The Grayken Center has several initiatives in place aimed at improving NAS treatment and we look forward to continued research collaborations that will yield the information necessary to provide the best, evidence-based treatment for NAS.”
This study was done in collaboration with Massachusetts General Hospital.
Boston MedTalks: Boston Medical Center’s Original Podcast Series
Podcasts have been around for some time now, but they’ve recently gained newfound popularity. Boston MedTalks, makes it easier for you to receive useful health and wellness information on the go!
This original series, launched in February 2017, brings our medical experts directly to your computer or mobile device. Let BMC’s experts enlighten you on a variety of topics, spanning from practical health information like how to stay healthy during flu season, to larger hospital-wide initiatives, like BMC’s investment to support new community housing to better the lives of our patients. Wherever your interest lies, Boston MedTalks has you covered.
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New episodes are released on Tuesdays. Listen at BMC.org/podcasts, or search ‘Boston MedTalks’ on iTunes or iHeartRadio.