Cultured Stem Cells — Court Rules on the Regenexx Case | K&L Gates LLP - JDSupra

Cultured Stem Cells — Court Rules on the Regenexx Case | K&L Gates LLP - JDSupra

A sad day.

The Effect of Smoking on Ligament and Cartilage Surgery in the Knee

The Effect of Smoking on Ligament and Cartilage Surgery in the Knee

A Systematic Review

1. Praveen Kanneganti, MD*,
2. Joshua D. Harris, MD*,
3. Robert H. Brophy, MD†,
4. James L. Carey, MD, MPH‡,
5. Christian Lattermann, MD§ and
6. David C. Flanigan, MD*,‖

+ Author Affiliations

1. ^*The Ohio State University Sports Medicine Center and Cartilage Restoration Program, Columbus, Ohio
2. ^†Department of Orthopedic Surgery, Washington University School of Medicine, St Louis, Missouri
3. ^‡Penn Center for Advanced Cartilage Repair and Osteochondritis Dissecans Treatment Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
4. ^§Department of Orthopaedic Surgery and Sports Medicine, University of Kentucky, Lexington, Kentucky
5. Investigation performed at The Ohio State University Sports Medicine Center, Columbus, Ohio

1. ↵‖David C. Flanigan, MD, The Ohio State University Sports Medicine Center, 2050 Kenny Rd, Suite 3100, Columbus, OH 43221-3502 (e-mail: david.flanigan@osumc.edu).

Abstract

Background: The adverse effects of smoking on various health conditions such as cancer, diabetes, and cardiovascular disease have been well documented. Many orthopaedic conditions, such as fracture healing, wound repair, and bone mineral density, have been reported to be adversely affected by smoking. However, no known systematic reviews have investigated the effects of smoking on ligament and cartilage knee surgery.

Purpose: We hypothesized that smoking would have a negative influence from both a basic science and clinical outcome perspective on these types of knee surgeries.

Study Design: Systematic review.

Methods: A systematic review of multiple medical databases was performed evaluating clinical and basic science studies to determine the effects of smoking on ligament and cartilage knee surgery.

Results: Fourteen studies were found for inclusion and analysis. Eight of these studies addressed the relationship between smoking and knee ligaments, and 6 investigated the relationship between smoking and articular cartilage. With the exception of 1, all of the basic science and clinical studies exploring the relationship between smoking and knee ligaments found a negative association of smoking, either molecularly, biomechanically, or clinically. One basic science and 3 clinical studies found a negative influence of smoking on articular cartilage of the knee. No studies were found that investigated the relationship of smoking and menisci.

Conclusion: The current literature reveals a negative influence of smoking on the results of knee ligament surgery, both from a basic science and clinical perspective, implying that smoking cessation would benefit patients undergoing these procedures. The association between smoking and knee articular cartilage was less clear, although the literature still suggests an overall negative influence and highlights the need for further investigation.

Keywords:

• smoking
• nicotine
• meniscus
• articular cartilage
• anterior cruciate ligament
• knee

New hydrogel may help cartilage regeneration research | Orthopedics

New hydrogel may help cartilage regeneration research | Orthopedics

New hydrogel may help cartilage regeneration research

• September 24, 2012

A new synthesized hydrogel may help replace lost cartilage in joint replacement patients with osteoarthritis, according to Harvard researchers.

“For a gel to work in those settings, it has to be able to stretch and expand under compression and tension without breaking,” Jeong-Yun Sun, a postdoctoral fellow at the Harvard School of Engineering and Applied Sciences, stated in a press release.
Using a combination of polyacrylamide and alginate, the synthesized gel can stretch up to 21 times its size and is stronger than gels formed by either material alone, researchers said. Compared to other hydrogels often used as scaffolds for cartilage regeneration, this new “super gel” maintains its mechanical stability and elasticity over multiple stretches.
Sun and colleagues found that, even after the gel cracked, it was able to stretch to 17 times its own size. The researchers said they hope the gel will be an alternative to more invasive-based approaches, such as autologous chondrocyte implantation or joint replacement, in the treatment of patients with osteoarthritis.

Clinician calls for further study on platelet-rich plasma formulations and impact

Clinician calls for further study on platelet-rich plasma formulations and impact

• Orthopedics Today, September 2012

MONTREAL — While there is evidence of successful treatment using platelet-rich plasma for various pathologies, the lack of unfailing positive clinical outcomes points to variability among patients and materials, according to a lecturer at the International Cartilage Repair Society World Congress 2012.

In his lecture, Scott A. Rodeo, MD, described his and others’ clinical experiences with platelet-rich plasma (PRP). His message — more research is needed about these materials and understanding the variability inherent in PRP formulations, patients and their pathologies is key.
“One of the fundamental issues, as a clinician if you are thinking of using PRP, is the tremendous variability,” Rodeo, of the Hospital for Special Surgery in New York, said. “All PRPs are not the same. There is variability between the various commercial systems that are available. There is also variability, of course, within the individual patient and the underlying biology.”

 

Scott A. Rodeo

He noted that cytokines influence several biological aspects of connective tissue.
“Clearly, connective tissue healing requires a complex timing and sequence of cytokine expression, so the rationale and attraction of PRP is the ability to deliver numerous cytokines in potentially physiologically relevant proportions,” Rodeo said. “It is complex, and it is a bit of a leap of faith. In fact, despite vast basic science and laboratory data [that] demonstrate a positive effect of PRP on these tissues, this has not translated into a consistently positive clinical effect.”

Variability

A reason for this, Rodeo suggested, could be that PRP formulations differ among manufacturers and patients. Even within each individual, formulations can vary throughout the day.
With these variations, it becomes impossible to determine whether a formulation that works in one study will have the same effect in another patient for a similar application or what may be the content of a given formulation.
“What are we putting in the patient? With a drug, it is easy. We know it is a precise composition,” Rodeo said. “That contrasts with the PRP materials we are using in patients.”

Arthritis treatment

Although a number of studies have demonstrated a clinical improvement in symptoms after PRP injections for the treatment of arthritis, Rodeo noted that most of the data available refer only to the knee.
“There is little data for other joints,” he said. “Most studies do report better results in younger patients with lesser degrees of degeneration. The clinical effect typically wears off in 6 months to 12 months. There is little data demonstrating a positive structural effect — that is, actual cartilage regeneration — so it may be symptom-modifying but it is probably not structure-modifying.”
Rodeo noted that more research is needed about PRP.
“We certainly need more information,” he said. “Keep in mind, arthritis is a heterogeneous condition. The effect of a specific PRP formulation may differ significantly based on the underlying biologic or inflammatory milieu.”
He added, “Clinical results, clearly, are mixed. PRP seems to have the potential to be symptom-modifying, but clearly [it] does not appear to be structure-modifying.”
With regard to the variability of PRP, Rodeo noted clinicians must strive to understand what they are delivering to the patient. This means analyses of PRP samples, so these formulations can be correlated with clinical results.
“We know cytokines can increase production of matrix proteins, but a critical deficiency with all this work is that tissue microstructure is not reformed,” Rodeo said. “We do not regenerate normal cartilage, tendon or meniscus. [It] appears growth factors, such as PRP, still do not provide the proper cellular and molecular signals to truly drive regenerative healing. I would submit that both cells and the signals are needed to reconstitute both tissue composition and structure.” – by Robert Press

Reference:

• Rodeo SA. Clinical experience with platelet-rich plasma. Paper 15.1.3. Presented at the International Cartilage Repair Society World Congress 2012. May 12-15. Montreal.

Highly stretchable and tough hydrogels : Nature : Nature Publishing Group

Highly stretchable and tough hydrogels : Nature : Nature Publishing Group

Highly stretchable and tough hydrogels

• Jeong-Yun Sun,
• Xuanhe Zhao,
• Widusha R. K. Illeperuma,
• Ovijit Chaudhuri,
• Kyu Hwan Oh,
• David J. Mooney,
• Joost J. Vlassak
• & Zhigang Suo

Nature

489,

133–136

(06 September 2012)

doi:10.1038/nature11409

Received

16 February 2012

Accepted

10 July 2012

Published online

05 September 2012

Hydrogels are used as scaffolds for tissue engineering¹, vehicles for drug delivery², actuators for optics and fluidics³, and model extracellular matrices for biological studies⁴. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour⁵. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels^{6, 7} have achieved stretches in the range 10–20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m⁻² (ref. 8), as compared with ~1,000 J m⁻² for cartilage⁹ and ~10,000 J m⁻² for natural rubbers¹⁰. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties^{11, 12, 13, 14, 15, 16, 17, 18}; certain synthetic gels have reached fracture energies of 100–1,000 J m⁻² (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ~90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ~9,000 J m⁻². Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels’ toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.

The Madman :: How I Became a Madman

The Madman :: How I Became a Madman

You ask me how I became a madman. It happened thus: One day, long before many gods were born, I woke from a deep sleep and found all my masks were stolen -- the seven masks I have fashioned and worn in seven lives, -- I ran maskless through the crowded streets shouting, "Thieves, thieves, the curséd thieves."

Men and women laughed at me and some ran to their houses in fear of me.
And when I reached the market place, a youth standing on a house-top cried, "He is a madman." I looked up to behold him; the sun kissed my own naked face for the first time. For the first time the sun kissed my own naked face and my soul was inflamed with love for the sun, and I wanted my masks no more. And as if in a trance I cried, "Blessed, blessed are the thieves who stole my masks."
Thus I became a madman.
And I have found both freedom and safety in my madness; the freedom of loneliness and the safety from being understood, for those who understand us enslave something in us.
But let me not be too proud of my safety. Even a Thief in a jail is safe from another thief.

Stem cells bring back feeling for paralysed patients - health - 03 September 2012 - New Scientist

Stem cells bring back feeling for paralysed patients - health - 03 September 2012 - New Scientist

Stem cells bring back feeling for paralysed patients

• 14:38 03 September 2012 by Andy Coghlan
• For similar stories, visit the Stem Cells Topic Guide

For the first time, people with broken spines have recovered feeling in previously paralysed areas after receiving injections of neural stem cells.

Three people with paralysis received injections of 20 million neural stem cells directly into the injured region of their spinal cord. The cells, acquired from donated fetal brain tissue, were injected between four and eight months after the injuries happened. The patients also received a temporary course of immunosuppressive drugs to limit rejection of the cells.

None of the three felt any sensation below their nipples before the treatment. Six months after therapy, two of them had sensations of touch and heat between their chest and belly button. The third patient has not seen any change.

"The fact we've seen responses to light touch, heat and electrical impulses so far down in two of the patients is very unexpected," says Stephen Huhn of StemCells, the company in Newark, California, developing and testing the treatment. "They're really close to normal in those areas now in their sensitivity," he adds.

"We are very intrigued to see that patients have gained considerable sensory function," says Armin Curt of Balgrist University Hospital in Zurich, Switzerland, where the patients were treated, and principal investigator in the trial.

The data are preliminary, but "these sensory changes suggest that the cells may be positively impacting recovery", says Curt, who presented the results today in London at the annual meeting of the International Spinal Cord Society.

Persistent gains

The patients are the first three of 12 who will eventually receive the therapy. The remaining recipients will have less extensive paralysis.

"The sensory gains, first detected at three months post-transplant, have now persisted and evolved at six months after transplantation," says Huhn. "We clearly need to collect much more data to demonstrate efficacy, but our results so far provide a strong rationale to persevere with the clinical development of our stem cells for spinal injury," he says.

"We need to keep monitoring these patients to see if feeling continues to affect lower segments of their bodies," says Huhn. "These are results after only six months, and we will follow these patients for many years."

Huhn says that the company has "compelling data" from animal studies that the donated cells can repair nerves within broken spines (Neurological Research, DOI: 10.1179/016164106X115116).

There could be several reasons why the stem cells improve sensitivity, says Huhn. They might help to restore myelin insulation to damaged nerves, improving the communication of signals to and from the brain. Or they could be enhancing the function of existing nerves, replacing them entirely or reducing the inflammation that hampers repair.

Abandoned trial

The announcement comes almost a year after the world's only other trial to test stem cells for spinal injury was suspended. Geron of Menlo Park, California, had injected neural stem cells derived from embryonic stem cells into four people with spinal injuries when it announced that it was going to focus on cancer therapies instead. The company also abandoned its other stem-cell programmes combating diabetes, heart disease and arthritis.

Huhn hopes that the results from the StemCells trial will revive the enthusiasm that evaporated following Geron's bombshell. "It's the first time we've seen a signal of some beneficial effect, so we're moving in the right direction, and towards a proof of concept," he says.

The news was welcomed by other pioneers of neural stem-cell research. "It looks encouraging and has some parallels with what we've seen in our trial in stroke patients," says Michael Hunt, CEO of ReNeuron, in Guildford, UK, which in 2010 became the first company in the world to treat strokes with stem cells.

"They appear to be making progress, and that's good for the stem-cell field generally, and for neural stem-cell research in particular," says Hunt. He says that seven people who have had strokes have now been treated, and that some have shown signs of functional improvement without adverse effects.

"It's early days, and we are proceeding cautiously before hopefully moving to more substantive trials," says Hunt.

"These initial data certainly indicate that stem-cell transplantation may help remediate some of the severe functional loss associated with spinal cord injury," says George Bittner of the University of Texas at Austin, who has developed a polymer-based system for rapid treatment of damaged nerves.

But, he says, a single mode of treatment is unlikely to be enough to restore function after spinal cord injuries. We will need "combinations of approaches including stem cells, polymer-based treatments, retraining and physical therapy".

Other researchers were intrigued but cautious. "It's work in progress," says Wagih El Masri, a spinal specialist at the Midlands Centre for Spinal Injuries in Oswestry, UK, who attended Curt's presentation. "We need larger numbers of patients treated to confirm whether this interesting finding has any future."

He says that about 3 per cent of patients show similar improvements spontaneously at about 6 months, but seldom beyond that. Testing the therapy on patients who were injured more than six months before would help to confirm that the stem cells are responsible for the results.