Rib regeneration in both humans and mice
Unlike salamanders, mammals can't regenerate lost limbs, but they can repair large sections of their ribs.
In adult mice, surgically removed sections of either portion can fully regenerate.
In a new study in the Journal of Bone and Mineral Research, a team directed by University of Southern California (USC; Los Angeles) Stem Cell researcher Francesca Mariani takes a closer look at rib regeneration in both humans and mice. The first author of the paper, USC medical student Marissa Srour, was a USC undergraduate when she started the project, which earned a 2011 USC Discovery Scholar Prize. Each year, 10 graduating seniors win these coveted prizes, which recognize exceptional new scholarship.
Using CT imaging, Srour, Mariani and their colleague Janice Lee from the University of California, San Francisco, monitored the healing of a human rib that had been partially removed by a surgeon. The eight centimeters of missing bone and one centimeter of missing cartilage did partially repair after six months.
To better understand this repair process, they surgically removed sections of rib cartilage – ranging from three to five millimeters – from a related mammal, mice. When they removed both rib cartilage and its surrounding sheath of tissue - called the "perichondrium," the missing sections failed to repair even after nine months. However, when they removed rib cartilage but left its perichondrium, the missing sections entirely repaired within one to two months.
They also found that a perichondrium retains the ability to produce cartilage even when disconnected from the rib and displaced into nearby muscle tissue – further suggesting that the perichondrium contains progenitor or stem cells.
"We believe that the development of this model in the mouse is important for making progress in the field of skeletal repair, where an acute clinical need is present for ameliorating skeletal injury, chronic osteoarthritis and the severe problems associated with reconstructive surgery," said Mariani, assistant professor of Cell and Neurobiology and principal investigator in the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC. "At the early stages in our understanding, the mouse provides us with an exceptional ability to make progress, and we are excited about the potential for using cells derived from the rib perichondrium or using rib perichondrium-like cells for regenerative therapy."
Spinal discs provide a window into our evolutionary past
Thoughts of the family tree may not be uppermost in the mind of a person suffering from a slipped disc, but those spinal discs provide a window into our evolutionary past. They are remnants of the first vertebrate skeleton, whose origins now appear to be older than had been assumed. Scientists at the European Molecular Biology Laboratory (EMBL; Heidelberg, Germany), have found that, unexpectedly, this skeleton most likely evolved from a muscle. The study, carried out in collaboration with researchers at the Howard Hughes Medical Institute in Janelia Farm (Ashburn, Virginia) is published in Science.
Humans are part of a group of animals called chordates, whose defining feature is a rod of cartilage that runs lengthwise along the middle of their body, under their spinal chord. This structure, called the notochord, was the first vertebrate skeleton. It is present in human embryos, and is replaced with the backbone as we develop, with the cartilage reduced to those tell-tale discs. Since starfish, sea urchins and related animals have no such structure, scientists assumed the notochord had emerged in a relatively recent ancestor, after our branch of the evolutionary tree split away from the 'starfish branch'.
"People simply haven't been looking beyond our direct relatives, but that means you could be fooled, if the structure appeared earlier and that single group lost it," says Detlev Arendt from EMBL, who led the study. "And in fact, when we looked at a broader range of animals, this is what we found."
Researchers in Arendt's lab, identified the genetic signature of the notochord – the combination of genes that have to be turned on for a healthy notochord to form. When they found that the larva of the marine worm Platynereis has a group of cells with that same genetic signature, the scientists teamed up with Philipp Keller's group at Janelia Farm to use state-of-the-art microscopy to follow those cells as the larva developed. They found that the cells form a muscle that runs along the animal's midline, precisely where the notochord would be if the worm were a chordate. The researchers named this muscle the axochord, as it runs along the animal's axis. A combination of experimental work and combing through the scientific literature revealed that most of the animal groups that sit between Platynereis and chordates on the evolutionary tree also have a similar, muscle-based structure in the same position.
The scientists reason that such a structure probably first emerged in an ancient ancestor, before all these different animal groups branched out on their separate evolutionary paths. Such a scenario would also explain why the lancelet amphioxus, a 'primitive' chordate, has a notochord with both cartilage and muscle. Rather than having acquired the muscle independently, amphioxus could be a living record of the transition from muscle-based midline to cartilaginous notochord.
The shift from muscle to cartilage could have come about because a stiffened central rod would make swimming more efficient, the scientists postulate.
MRI and PET used to monitor the
bone metastasese treatment response
Imaging technologies are very useful in evaluating a patient's response to cancer treatment, and this can be done quite effectively for most tumors using RECIST, Response Evaluation Criteria in Solid Tumors. However, RECIST works well for tumors located in soft tissue, but not so well for cancers that spread to the bone, such as is the case for prostate and breast cancers. More effort, therefore, is needed to improve our understanding of how to monitor the response of bone metastases to treatment using MRI and PET, and a recent EORTC Imaging Group review and position statement published in the European Journal of Cancer is a decidedly welcome contribution.
Most recent developments in MRI and PET elucidates how these techniques can be used to detect bone metastases at an early stage as well as monitor the response of these to treatment.
EORTC Imaging Group The paper published by these EORTC Imaging Group investigators highlights the most recent developments in MRI and PET and elucidates how these techniques can be used to detect bone metastases at an early stage as well as monitor the response of these to treatment. They describe the current state of the art in PET and MRI, the strengths, weaknesses and complementarity of various imaging techniques with respect to specific indications, and recommendations for choosing the most appropriate imaging technique.
Frederic Lecouvet of the Cliniques Universitaires Saint Luc (Brussels) and lead author of this review and position statement sai, "Assessing the response of metastases to treatment is something we do on a day to day basis, both in our oncology practice as well as for clinical trials. If the metastases occur in soft tissues, then we already have validated criteria, such as RECIST, that enable us to evaluate the response. A host of problems, however, limits our ability to measure the response to treatment of metastases found in bone. These range from the characteristics of bone metastatic disease, the structure of bone itself, to the sensitivity, specificity, and resolution of imaging methods available until now. We hope to resolve these issues, and our review is a step in the right direction."
Techniques such as MRI and PET have the potential to detect the spreading of a cancer into the bone marrow at an earlier stage and also determine the extent of this spread, and the efforts of the EORTC researchers will go a long way towards making these techniques a routine part of oncology practice.
Rotation Medical initiates post-market clinical study
Rotation Medical (Plymouth, Minnesota), a device company focused on developing new technologies to treat rotator cuff disease, has initiated a multi-center post-market clinical study evaluating the use of the Rotation Medical rotator cuff system in treating supraspinatus rotator cuff tendon tears. The study will be conducted with orthopedic and sports medicine surgeons across the U.S., including Ted Schlegel, from Steadman Hawkins Clinic, Jeffrey Abrams, from Princeton Orthopaedic Associates and Timothy Codd, from Towson Orthopaedic Associates/University of Maryland Medical System, among others.
"The information that we gain from this post-market clinical trial will expand the body of evidence documenting the value of the Rotation Medical technology and advance our mission to provide relief for patients by reversing rotator cuff disease progression and restoring long-term shoulder function," said Martha Shadan, president/CEO of Rotation Medical.
The study will evaluate tendon healing and growth of new tendinous tissue after the implantation of a Rotation Medical bioinductive implant that is used as either a standalone treatment for tendon tears or as an adjunct to surgical repair. Patients will undergo magnetic resonance imaging to assess post-operative changes in tendon thickness, tendon quality, and tear size. Researchers will also evaluate shoulder function using the American Shoulder & Elbow Surgeons' (ASES) Survey and Constant Shoulder Score and analyze recovery outcomes including sling time, return to work, and physical rehabilitation. Study patients will be followed for two years after surgery.
"There are many limitations associated with the current standard of care for treating rotator cuff diseases and until this point, there has been no proven reproducible therapy to induce tendinous tissue and that has the potential to prevent the disease from progressing. As a consequence, many patients delay treatments, face lengthy rehabilitation or experience a high rate of re-tears," said Schlegel, lead investigator for the study. "This trial will add to the growing body of pre-clinical and clinical data evaluating the use of this bioinductive implant technology to improve healing at the tendon and bone interface with the goal of addressing these challenges."
Rotation Medical received 510(k) clearance from the FDA for its implantable bioinductive implant technology in March. The Rotation Medical rotator cuff system is commercially available in the U.S.