TOBI Faculty Publications: April 2017

May 23

TOBI Faculty Publications: April 2017

Below is a resource of all April 2017 regenerative medicine publications authored by TOBI Speakers and Faculty, including alumni faculty. Each month, we compile a list with links and brief summaries of all new research and studies to keep TOBI community members informed and on the cutting edge of regenerative medicine research. Studies are listed alphabetically by TOBI Faculty names.

If you are a TOBI Faculty member or alumni and would like your publications included in the TOBI monthly publications blog, please send it to

6 April 2017, Rheumatology
Rhuematoid Arthritis: The ins and outs of platelets in R.A
TOBI 2017 Speaker Isabel Andia, PhD, reports on insights into the ability of platelets to modify lymphocyte biology suggest a potential anti-inflammatory role for platelet therapy in rheumatoid arthritis. The success of this therapy will depend on researchers being able to define the best formulation to manipulate the crosstalk between inflammatory, vascular and synovial cells.
See the full study here.

4 April 2017, The Journal of Ocular Pharmacology and Therapeutics
The Effect of Immunologically Safe Plasma Rich in Growth Factor Eye Drops in Patients with Sjögren Syndrome.
The objective of this study was to provide preliminary information about the efficacy and safety of immunologically safe plasma rich in growth factor (immunosafe PRGF) eye drops in the treatment of moderate to severe dry eye in patients with primary and secondary Sjögren’s syndrome (SS) and to analyze the influence of several variables on treatment outcomes. The study is co-authored by TOBI Faculty Alumni Eduardo Anitua MD, PhD.
See the full study here.

28 April 2017, Stem Cells Translational Medicine
Mesenchymal Stem Cells: Time to Change the Name!
Longtime TOBI Speaker Arnold I Caplan, PhD. often called “the father of the mesenchymal stem cell (MSC)”, pens a report arguing that it is time to change the name of MSCs. Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs. Today, there are hundreds of clinics and hundreds of clinical trials using human MSCs with very few, if any, focusing on the in vitro multipotential capacities of these cells. Unfortunately, the fact that MSCs are called “stem cells” is being used to infer that patients will receive direct medical benefit, because they imagine that these cells will differentiate into regenerating tissue-producing cells. Such a stem cell treatment will presumably cure the patient of their medically relevant difficulties ranging from osteoarthritic (bone-on-bone) knees to various neurological maladies including dementia. I now urge that we change the name of MSCs to Medicinal Signaling Cells to more accurately reflect the fact that these cells home in on sites of injury or disease and secrete bioactive factors that are immunomodulatory and trophic (regenerative) meaning that these cells make therapeutic drugs in situ that are medicinal. It is, indeed, the patient’s own site-specific and tissue-specific resident stem cells that construct the new tissue as stimulated by the bioactive factors secreted by the exogenously supplied MSCs.
See the full study here.

E-pub April 2017, Arthroscopy
Patient Understanding, Expectations, and Satisfaction Regarding Rotator Cuff Injuries and Surgical Management.
Rotator cuff injuries are among the most common in orthopaedics, with rotator cuff repair surgery consistently reported as one of the most commonly performed orthopaedic procedures. Patient satisfaction is becoming an increasingly important outcome metric as health care continues to evolve with regard to quality measures affecting physician reimbursement. TOBI Faculty Alumni Brian J. Cole, MD investigates patient expectations, satisfaction, and understanding in rotator cuff injury treatment. Evidence supports that postoperative patient satisfaction, an important quality outcome metric, is highly influenced by preoperative patient expectations, which are in turn governed by patient knowledge and understanding. Many authors have delineated patient-, injury-, and surgery-specific variables associated with high preoperative expectations and satisfaction after rotator cuff surgery. Specifically, large rotator cuff tears, subscapularis tears, persistence of postoperative pain and dysfunction, worker’s compensation cases, lower education level, and preoperative disability have been seen more frequently in patients reporting poor satisfaction. Others have reported variables associated with higher patient satisfaction such as being married, employed, and of older age at the time of surgery (>55 years old) predictive of higher satisfaction. Patient education preoperatively regarding details about the surgery and the postoperative plan both immediately after the procedure and for rehabilitation are critical in helping set patients’ preoperative expectations that have a known effect on patients’ subjective clinical outcomes.
See the full study here.

E-pub April 2017, International Journal of Sports Medicine
A Genetic Marker Associated with Shoulder Disclocation
TOBI 2017 Speakers & Faculty members Jason Dragoo, MD, and Michael Fredericson, MD, collaborate on this study investigate causes behind shoulder dislocations. Shoulder dislocations are common shoulder injuries associated with athletic activity in contact sports, such as football, rugby, wrestling, and hockey. Identifying genetic loci associated with shoulder dislocation could shed light on underlying mechanisms for injury and identify predictive genetic markers. To identify DNA polymorphisms associated with shoulder dislocation, a genome-wide association screen was performed using publically available data from the Research Program in Genes, Environment and Health including 662 cases of shoulder dislocation and 82 602 controls from the European ancestry group. rs12913965 showed an association with shoulder dislocation at genome-wide significance (p=9.7×10-9; odds ratio=1.6) from the European ancestry group. Individuals carrying one copy of the risk allele (T) at rs12913965 showed a 69% increased risk for shoulder dislocation in our cohort. rs12913965 is located within an intron of the TICRR gene, which encodes TOPBP1 interacting checkpoint and replication regulator involved in the cell cycle. rs12913965 is also associated with changes in expression of the ISG20 gene, which encodes an antiviral nuclease induced by interferons. This genetic marker may one day be used to identify athletes with a higher genetic risk for shoulder dislocation. It will be important to replicate this finding in future studies.
See the full study here.

5 April 2017, PM&R: The Journal of Injury, Function, & Rehabilitation
Integrating Musculoskeletal Education and Patient Care at Medical Student-Run Free Clinics.
Student-run free clinics (SRFCs) have emerged as an important educational component of United States (US) medical schools. Despite the prevalence of musculoskeletal (MSK) problems presenting to SRFCs, students and clinics are often unprepared to diagnose and to treat common MSK complaints. TOBI 2017 Faculty Michael Fredericson, MD, and coauthors sought to determine the scope of diagnosis and treatment at a medical student-run free clinic specializing in musculoskeletal care using physical medicine and rehabilitation (PM&R) residents. Secondary goals included reviewing student satisfaction and determining the appropriateness of the clinic in medical education. They concluded that SRFCs represent an underused opportunity to enhance MSK education among medical students by treating a variety of common MSK complaints in an underserved population.
See the full study here.

26 April 2017, International Orthopedics
History of clubfoot treatment, part I: From manipulation in antiquity to splint and plaster in Renaissance before tenotomy.
Idiopathic clubfoot is one of the most common problems in paediatric orthopaedics. The treatment is controversial and continues to be one of the challenges in paediatric orthopaedics. The aim of this review, by TOBI Faculty Alumni Philippe Hernigou, MD is to assess the different methods of clubfoot treatment used over the years in light of the documentation present in the literature and art paintings from the antiquity to the end of the 19th century. The aim of this paper is to review all treatment methods of the clubfoot over the years that were proposed to provide patients a functional, pain-free, normal-looking foot, with good mobility, without calluses, and requiring no special shoes. Hippocrates was the first to write references about treatment methods of clubfoot. After the Middle Ages and the Renaissance where patients were treated by barber-surgeons, quacks and charlatans, bonesetters, and trussmakers, there were more detailed studies on the disease, with the help of famous names in medicine such as Venel and Scarpa.
See the full study here.

20 April 2017, Journal of Addiction Medicine
High Mortality Among Patients with Opioid Use Disorder in a Large Healthcare System
New TOBI 2017 Faculty David Huang, MD, investigates elevated mortality among individuals with opioid use disorder (OUD) treated in addiction specialty clinics or programs. Information about OUD patients in general healthcare settings is needed in light of the current effort to integrate addiction services into primary healthcare systems. This study examined mortality rates, causes of death, and associated risk factors among patients with OUD in a large general healthcare system.
See the full study here.

17 April 2017, Pediatrics Rheumatology Online Journal
The new Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry: design, rationale, and characteristics of patients enrolled in the first 12 months.
In this publication, the authors, including TOBI 2017 Speaker Dallas Kingsbury, MD, describe the history, design, and rationale of the new Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry and present the characteristics of patients with juvenile idiopathic arthritis (JIA) enrolled in the first 12 months of operation. The CARRA Registry began prospectively collecting data in the United States and Canada in July 2015 to evaluate the safety of therapeutic agents in persons with childhood-onset rheumatic disease, initially restricted to JIA. Secondary objectives include the evaluation of disease outcomes and their associations with medication use and other factors. Data are collected every 6 months and include clinical assessments, detailed medication use, patient-reported outcomes, and safety events. Follow-up is planned for at least 10 years for each participant and is facilitated by a telephone call center. The new CARRA Registry successfully enrolled nearly 1200 participants with JIA in the first 12 months of its operation. Sustainable funding has been secured from multiple sources. The CARRA Registry may serve as a model for the study of other uncommon diseases.
See the full report here.

12 April 2017, Tissue Engineering
An Engineered Multiphase Three-Dimensional Microenvironment to Ensure the Controlled Delivery of Cyclic Strain and Human Growth Differentiation Factor 5 for the Tenogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells.
At present, injuries or rupture of tendons are treated by surgical repair or conservative approaches with unpredictable clinical outcome. Alternative strategies to repair tendon defects without the undesirable side effects associated with the current options are needed. With this in mind, a tissue engineering approach has gained considerable attention as a promising strategy. Here, TOBI 2017 Speaker Nicola Maffulli, MD, PhD, investigated a synthetic three-dimensional (3D) microenvironment able to interact with stem cells and inducing, via coupled biochemical and physical signals, their early commitment toward the tenogenic lineage. Their approach opens exciting perspectives for future development of engineered tendon tissue substitutes.
See the full study here.

1 April 2017, Journal of Vascular and Interventional Radiology
Midterm Clinical Outcomes and MR Imaging Changes after Transcatheter Arterial Embolization as a Treatment for Mild to Moderate Radiographic Knee Osteoarthritis Resistant to Conservative Treatment.
The purpose of this study, by TOBI Faculty Alumni Yuji Okuno, is to describe the safety and efficacy of transcatheter arterial embolization for mild to moderate radiographic knee osteoarthritis (OA) that is resistant to conservative treatment. This prospective study included 72 patients (95 knees) with OA of Kellgren-Lawrence (KL) grade 1-3 and persisting moderate to severe pain that was resistant to conservative management who were treated with transcatheter arterial embolization between July 2012 and March 2016. Clinical outcomes were evaluated at 1, 4, and 6 months and then every 6 months for a maximum of 4 years. The Whole-Organ Magnetic Resonance Imaging Score (WORMS) was evaluated at baseline and at 2 years after embolization in 35 knees.
See the full study here.

26 April 2017, Knee Surgery, Sports Traumatology, Arthroscopy
The iliotibial bando and anterolateral capsule have a combined attachment to the Segond fracture.
The purpose of this report, by TOBI 2017 Faculty Kentaro Onishi, DO, was to describe the injury mechanism, surgical findings, and outcomes in a 21-year-old professional female football player who presented with a complete anterior cruciate ligament (ACL) rupture and Segond fracture. Interview and video analysis were performed to elicit the injury mechanism. Clinical examination and imaging revealed a complete ACL tear, Segond fracture, lateral meniscus tear, MCL sprain, and posterolateral corner sprain.
See the full study here.

8 April 2017, Journal of Ultrasound in Medicine
Sonographic Visualization of the Posterior Cutaneous Nerve of the Forearm: Technique and Validation Using Perineural Injections in a Cadaveric Model.
In this study, longtime TOBI 2017 Speaker & Faculty Jay Smith, MD, determines the ability to sonographically identify the posterior cutaneous nerve of the forearm (PCNF) and its distal epicondylar branches using sonographically guided perineural injections in an unembalmed cadaveric model. He and co-authors concluded that high-resolution sonography can identify the PCNF and its distal epicondylar branches. Sonographic evaluation of the PCNF should be included in the evaluation of patients presenting with refractory or atypical lateral elbow pain syndromes. Diagnostic and therapeutic sonographically guided procedures targeting the PCNF or its lateral epicondylar branches are feasible and warrant further investigation.
See the full study here.

E-pub April 2017, Journal of Tissue Engineering and Regenerative Medicine
Efficacy of thermoresponsive, photocrosslinkable hydrogels derived from decellularized tendon and cartilage extracellular matrix for cartilage tissue engineering.

Tissue engineering using adult mesenchymal stem cells (MSCs), a promising approach for cartilage repair, is highly dependent on the nature of the matrix scaffold, writes TOBI 2017 Speaker Rocky Tuan, PhD, in his recent study. Thermoresponsive, photocrosslinkable hydrogels were fabricated by functionalizing pepsin-soluble decellularized tendon and cartilage extracellular matrices (ECM) with methacrylate groups. Methacrylated gelatin hydrogels served as controls. When seeded with human bone marrow mesenchymal stem cells (MSCs) and cultured in chondrogenic medium, methacrylated ECM hydrogels experienced less cell-mediated contraction, as compared against non-methacrylated ECM hydrogels. However, methacrylation slowed or diminished chondrogenic differentiation of seeded MSCs, as determined through analyses of gene expression, biochemical composition, and histology. In particular, methacrylated cartilage hydrogels supported minimal chondrogenesis over 42 weeks, as hydrogel disintegration beginning at day 14 presumably compromised cell-matrix interactions. As compared against methacrylated gelatin hydrogels, MSCs cultured in non-methacrylated ECM hydrogels exhibited comparable expression of chondrogenic genes (Sox9, Aggrecan, and collagen type II) but increased collagen type I expression. Non-methacrylated cartilage hydrogels did not promote chondrogenesis to a greater extent than either non-methacrylated or methacrylated tendon hydrogels. Whereas methacrylated gelatin hydrogels supported relatively homogenous increases in proteoglycan and collagen type II deposition throughout the construct over 42 days, ECM hydrogels possessed greater heterogeneity of staining intensity and construct morphology. These results do not support the utility of pepsin-solubilized cartilage and tendon hydrogels for cartilage tissue engineering over methacrylated gelatin hydrogels. Methacrylation of tendon and cartilage ECM hydrogels permits thermal- and light-induced polymerization but compromises chondrogenic differentiation of seeded MSCs.
See the full study here.

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