Embryonic Stem Cells used to Treat Spinal Cord Injury Patient

For the first time in history, embryonic stem cells have been used to treat a patient with an acute spinal cord injury.  According to several reports the protocol calls for using the treatment within two weeks of the initial injury.  Geron, the company sponsoring the trial has spent years and tens of millions of dollars just to get to this first patient.  The hope is for this first phase that safety can be demonstrated.

We have officially entered the era of biologic medicine.  For quite some time there has been promise, now there is action.  It is hard to compute the amount of effort that has likely gone into getting to just this point.  It is the researchers and especially this first brave but tragic patient that deserve the credit for this advancement.

In the future, the use of either adult stem cells or induced pluripotent stem cells may become a better option.  For now, regardless of your stance on the ethics of embryonic stem cells this day must be marked as a milestone.

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Sports Illustrated Platelet Rich Plasma Article

Sports Illustrated recently published an article about platelet rich plasma.

"While Galea's use of PRP on Tiger Woods and other athletes has stirred debate, the technique is not particularly new. Allan Mishra, adjunct clinical assistant professor of orthopedic surgery at the Stanford University Medical Center and a pioneer of PRP therapy, has been using it for nearly a decade. In a breakthrough study last year based on work by Mishra, PRP therapy performed significantly better than cortisone -- and with fewer side effects since it makes use of the patient's own blood -- in the treatment of chronic lateral elbow tendinosis, aka tennis elbow. "I can say pretty definitively that PRP is a reasonable choice for tendon [injuries]," Mishra says. "Now it needs to be studied in other applications."


The breakthrough study was actually performed by Dr. Taco Gosens from the Netherlands.  He and his colleagues have published the best clinical data to date on the use of platelet rich plasma for tendinopathy.  
To read more of the SI article, click here


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AAOS Discussion about Platelet Rich Plasma

The American Academy of Orthopaedic Surgery recently published a expert panel discussion about platelet rich plasma (PRP).  Its goal was to help clarify the many issues surrounding this novel therapy.  Dr. Allan Mishra, Dr. Freddie Fu, Dr. Steven Arnoczky and Dr. Jo Hannafin participated.  Below is an excerpt from the article:

Dr. Hannafin: I did a Google search and found more than 400,000 citations for PRP treatment, including YouTube videos on how the procedure is performed. Clearly, patients, physicians, and scientists are interested in the use of PRP. What conditions is PRP being used for?

Dr. Mishra: I use it almost exclusively in treating tendinopathy, particularly chronic tendinopathy that has failed to respond to other treatment modalities. That would include conditions such as chronic, recalcitrant lateral epicondylitis, patellar tendinopathy, and Achilles tendinopathy. I think the data—and the work that I have been doing for almost a decade now—provide the greatest support for its use in that area.

To read more of the article, click here.

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Stanford Football Player may start after PRP San Francisco Chronicle

Tom Fitzgerald of the San Francisco Chronicle wrote an article about a Stanford football player who may start after being treated with platelet rich plasma.  To read more, click here.

There is now mounting evidence that a specific type of PRP that contains increased concentrations of platelets AND white blood cells has value in the treatment of chronic tendinopathy.  Several studies are underway and some will soon be published. 

To view more about PRP and sports medicine videos, go to HalfDome.tv

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Stem Cell Video Description

This is a video describing stem cells.  It helps with understanding why stem cells are being studied for a variety of problems including heart disease and cancer.  Harvesting the value of these cells and other treatments such as platelet rich plasma will transform how we take care of patients within the next five years.

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High School Stem Cell Course

In the San Francisco Bay Area, it is now possible to begin studying stem cell biology in high school.  This is an important and interesting development.  If we can expose young men and women to this exciting and new field early, they will lead to discoveries we can now only dream of today. 

To read more about this new program:  click here.

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Trial of Embryonic Stem Cells for Spinal Cord Injury

The FDA lifted a hold on Geron's trial of embryonic stem cells to treat spinal cord injuries.  Geron hopes to begin the trial by the end of the year.  The specific cell line in use for this trial is GRNOPC1 which contains cells called oligodendrocyte progenitor cells. 

This is an interesting development.  Geron's stock popped 17% ($80-90 million in market cap) today on the news.  That speaks to the importance of a regulatory pathway for novel biologic treatments.  With the value in their stock, they can fund at least part of the trial.

Any thoughts out there on how to best fund new biologic treatments through the early clinical stages?

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Personalized Medicine

We are at the beginning of Personalized Medicine.  This concept can take many forms.  It can mean an evaluation the DNA of a breast cancer that predicts a poor prognosis.  (Overexpression of the human epidermal growth factor receptor type 2, HER2)  It can also mean a diagnostic test to determine if a patient will response to a specific type of cancer treatment like Gleevec (imatinib).  Recently, several companies have started offering over the counter DNA tests.  These are presently being evaluated by the FDA because of concerns for consistently and how they will be interpreted. 

On the horizon are also various autologous (your own) engineering treatments such as stem cells from your bone marrow or fat to treat heart disease.  Platelet rich plasma is another form of personalized medicine that has evolved rapidly in orthopedics and sports medicine.

An important question is who will pay for the continued development of these diagnostic tools and treatments?  The present macro health care environment is all about covering more patients with less money.  The micro enviroment (patients coming into the office) are demanding access to these new tests and treatments without regard to cost.  We will have to solve this fundamental conflict sooner than later.  It is not possible to have both.

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How to Grow an Ear...

Regnereative medicine is simply exploding.  New body parts are now being grown in the lab.

See a video of Dr. Tony Atala in his lab at Wake Forest growing an ear.  Simply amazing.

Video of how to grow an ear

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Platelet Rich Plasma used to treat Nadal's Knees

 
It appears as if Nadal has had his creaky knees treated with platelet rich plasma.  He has described it himself but only incompletely.  What we do not know is what type of PRP was used,  how it was injected and how he is being treated after the procedure.  These are all critical issues.  Presently, PRP with platelet concentrations around 5x baseline combined with concentrated white blood cells has the best published data supporting its use. 

It is clear that Nadal has chronic, severe tendonitis also know as tendinopathy.  It will help all of us who are studying how to best use PRP we knew more about his specific treatment.  Does anyone out there know any of the details?

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Orthopedics Article

Dr. Allan Mishra recently had his commentary about the state of platelet rich plasma published in Orthopedics. 

Allan Mishra

Is PRP a better solution than cortisone for treating tendon injuries? If so, why? 

"Platelet-rich plasma is clearly a better treatment for tendon injuries than cortisone. A recent double-blind randomized trial found significantly better outcomes in the treatment of tennis elbow in patients who received PRP when compared to cortisone.^3,4 There is also a risk of dermal atrophy or even tendon rupture when using cortisone. For these reasons, I rarely, if ever, use cortisone in the treatment of a tendon problem in my practice."

Read more of the article...


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Orthopedics Today PRP Discussion

Orthopedics Today recently published a discussion about platelet rich plasma.  Dr. Allan Mishra, Dr. Steven Arnoczky, Dr. Freddie Fu and Dr. Nicolas Sgaglione commented about the state of PRP. 


“The lay press does not understand the complexity of PRP,” Allan Mishra, MD, said. “As more data emerge, it will become clear to both physicians and surgeons that the specific formulation of PRP matters significantly in terms of bioactivity.” 

“The thing I would emphasize is that we have got to get a better understanding of the formulations in order to figure out whether PRP is valuable or not,” he added. “What is missing in the lay press – but also in the medical literature – is the discussion of what PRP is.”
Mishra pointed out that a formulation of PRP containing only concentrated platelets differs greatly from a formulation composed of concentrated platelets and white blood cells. 

Read more of the artilcle.... 

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Tennis Elbow PRP Discussion at ESSKA in Oslo, Norway

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Dr. Pietro Randelli moderated an excellent discussion of the treatment of tennis elbow (lateral epicondylitis) at the recent ESSKA meeting in Oslo, Norway.  Presentations about conservative care, platelet rich plasma injections and surgical treatment were given, including a debate about open versus arthroscopic techniques.  It is clear there are a variety of treatment options for this problem.  Platelet rich plasma is now considered a viable non-operative option.  Further data is presently being developed about the value of PRP vs surgery.  Stay tuned.

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Blood Spinning vs Blood Doping San Francisco Chronicle PRP

There is WAY too much confusion about the differences between blood spinning and blood doping.  Put simply, blood spinning is the separation of the whole blood into its components:  red blood cells, white blood cells, platelets and plasma.  Various techniques concentrate the components and then are used either individually or in combination.  Platelet rich plasma can be the product of blood spinning.  It is used immediately after preparation and for injuries.

Blood Doping is the collection and storage of typically whole blood to be used to enhance performance.  Blood is drawn, stored and then reinjected at later date typically right before a race to improve endurance.  Cyclist Floyd Lanis has recently admitted to blood doping and accused Lance Armstrong of the same. 

Gwen Knapp of the San Francisco Chronicle discusses these issues in conjunction with Dr. Tony Galea a Canadian doctor who has treated Tiger Woods and several other US athletes.  Read her article here.

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HalfDome.tv

Pac-10 Athletic Trainer Conference

Platelet rich plasma was discussed in depth at the Pacific 10 Athletic Trainer conference in Berkeley yesterday by Dr. Allan Mishra.  Almost all of the schools represented had used PRP to treat their athletes.  It was clear from the discussion, however, that the various forms of PRP (with and without white blood cells) were not well known to the group.  Moving forward, it was noted that the type of PRP should be recorded and studied in greater detail.  Also, the use of ultrasound to guide PRP injections and follow patients was found to have value.  Better and more specific post PRP protocols were found to be lacking.  Overall, it was interesting to note how much PRP was being used.  Clearly, the need for better indication data was still needed.  More later....

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LA Dodgers and Seattle Mariners using PRP to treat players

Seattle Mariner Cliff Lee pitched 7 innings yesterday of shut out baseball after receiving a platelet rich plasma injection for an abdominal strain.  The Safeco field crowd of 34,055 were treated to 93 mile per hour fast balls and eight strikeouts.  An impressive return to pitching. 

Did PRP help him in his return?  That is a good question to ask Mr. Lee.  Clearly, it didn't hurt him.  We need to follow his progress and better understand if PRP can treat abdominal strains and or sports hernia type injuries.

Los Angeles Dodger Rafael Furcal also has used PRP.  In his case, the platelet rich plasma was used to treat a hamstring injury.  We clearly need better data on whether PRP really helps these problems but for now it is clear that major league players and their doctors are using it.

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Ultrasound and Platelet Rich Plasma

 

Ultrasound of a Partial Elbow Extensor Tendon Tear

Ultrasound is a powerful non-invasive tool to evaluate soft tissue.  It can be especially helpful when imaging tendons.   Platelet rich plasma has been used extensively in tendinopathy and I believe ultrasound could provide an objective endpoint for future studies.  The size of the lesion could be measured before and after treatment.  Calculation of reduction of the pathologic hypoechogenic area could then be made.  We are beginning to evaluate a variety of ways to use ultrasound and would welcome any questions, comments or suggestions. 

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Mishra Platelet Rich Plasma Classification

Not all platelet rich plasma (PRP) is the same.  In order to be able to compare PRP, I am proposing a new classification system based on the presence or absence of white blood cells, activation status and platelet concentration.  Activation implies the use of thrombin and or calcium to cause the platelets to gel and release their bioactive molecules.  No activation implies in vivo activation by collagen. 

Platelet Concentration:   
A = 5 x baseline or higher
B =  Less than 5 x baseline

Type          White Blood Cells              Activation    

Type 1:       Increased WBCs                  Unactivated

Type 2:       Increased  WBCs                 Activated

Type 3:       Few/None WBCs                 Unactivated

Type 4:       Few/None WBCs                 Activated

Example:

Type 1A PRP:    Formulation with increased WBCs, 5.5x baseline platelets injected in an unactivated fashion.

The system is meant to be simple for now.  Clearly, there are other components to PRP including anticoagulation and buffering.  Importantly, new formulations may arise but for now we need a simple reproducible structure to discuss the different types of PRP.  I hope this represents a start.

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Platelet Rich Plasma and Abdominal Strains

Cliff Lee from the Seattle Mariners was recently treated with PRP for an abdominal strain.  This is a novel but potential valuable application for platelet rich plasma. Presently, there is no data to suggest it may work for this problem.  Basic science and preclinical work, however, suggest it may be helpful. 

I must applaud the doctors who made this choice because if it does help Mr. Lee return to the mound without surgery they will have helped many other athletes and physicians.  I would recommend, however, this case be documented in the medical literature so we all can follow the specifics.

As new potential applications arise, we must be aware of the value created by the researchers, physicians and patients who make that initial decision to try something that no one else has done. 

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Platelet Rich Plasma Debated at AAOS meeting in New Orleans

 Dr. Taco Gosens and Dr. Allan Mishra at AAOS New Orleans 2010

The concept of using platelet rich plasma for orthopedic applications was vigorously debated at the recent AAOS meeting in New Orleans.  Dr. Gosens presented his prospective randomized trial of 100 patients with chronic tennis elbow.  They found PRP was significantly better than cortisone at one year.  This has been published in the American Journal of Sports Medicine in Feb. 2010.  See Abstract

Dr. Gosens and his colleagues used PRP in a form that contains both concentrated platelets and white blood cells in an unactivated (no addition of thrombin or calcium) composition.  The details of this are critical as other forms of PRP may not have the same efficacy.  As the debate about PRP continues it will be paramount for researchers, clinicians and patients to understand that not all PRP is the same.  Presently, the lay press is trying to state that PRP either works or does not work.  This is too simple.  We need more studies such as the one presented by Dr. Gosens to understand when and where to apply PRP and in what form.  We may conclude from his study that unactivated platelets in combination with concentrated white blood cells is more effective than cortisone for chronic elbow tendinosis.  That is important.  More soon on the other data presented at AAOS on PRP. 

WebMD Article        

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Lindsay Vonn Gold Medal Olympic Downhill Whistler 2010

 

Linsday Vonn won the Gold Medal in the Olympic Downhill yesterday at Whistler.  Given the severity of her injury the performance was amazing.  I do not know any of the details of how she has been treated but kudos to her treating providers.  I still believe she should have been able to use platelet rich plasma as a means of treating her deep muscle bruise.  However she recovered and competed, she will now forever be known as an Olympic Champion.  

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US Olympian Daron Rahlves treated with Platelet Rich Plasma

US Olympic skier Daron Rahlves dislocated his hip at the Winter X Games recently.  He was treated with platelet rich plasma to help speed healing.   He is potentially going to compete in the Olympics this week.

We'll have to watch to see if he can recover in time.

Read the full story.

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Lindsay Vonn Olympics, Leg Injury and Platelet Rich Plasma

 

Olympian Lindsay Vonn apparently has a deep bruise to the muscle on her leg.  No one knows the details of the injury or how it is being treated but it sounds like it may be a good application for platelet rich plasma.  There is NO data suggesting PRP would help her other than accelerating her healing and obviously she has little or no time left before competition.

Does anyone out there have any comments on it would be a good idea to treat her with PRP?

Therapeutic Use Exemption for PRP in Muscle Injuries

It has been unclear in the media and in the literature if the World Anti-Doping Agency has banned platelet rich plasma for intramuscular injection.  There is a need to better understand their position.

Via BloodCure sources, we have definitely determined that PRP is LEGAL to be used via the intramuscular route with a therapeutic use exemption, also known as a TUE.  To my knowledge there is NO data suggesting PRP is anabolic for skeletal muscle injuries in humans.  If there is any specific data out there please post it here.

Athletes of all kinds need to know PRP may be an option for them if they apply for the appropriate exemption.  As always, check with the governing body of your chosen sport and consult with your physicians to best determine if it is appropriate.

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PRP beats Cortisone for Tennis Elbow in Level One Study

Under the direction of Dr. Taco Gosens from the Netherlands, a prospective, randomized, controlled trial of 100 patients was done to evaluate the efficacy of platelet rich plasma against cortisone for chronic tennis elbow.   They recently reported their results in the American Journal of Sports Medicine.  (Feb. 2010)

73% of the PRP treated patients were successful compared to 51% in the corticosteroid group (p < 0.001) at one year of follow up according to visual analog pain and functional scores.   This represents a 43% better success rate for PRP.    This data should put to end the option of using cortisone for chronic tennis elbow.  There is only limited support for its use in short term pain relief.  It is also clear from these last two papers that the evaluation of PRP must be done by specific clinical problem and the severity of the problem.  Only by doing careful studies we will be better able to predict which patients will respond to PRP as a therapy. 

Finally, PRP in my opinion should be reserved for patients that have failed non-operative treatment and are considering surgery.  Most patients with tendinopathy will respond without invasive intervention.  A study directly comparing PRP to surgical outcomes for tendinopathy should be considered.

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Platelet Rich Plasma JAMA Article

A recently published article by de Vos et al in JAMA has resulted in a flurry of lay press articles declaring platelet rich plasma (PRP) does not work.  Much like the overhype of PRP after Hines Ward was treated just before the Super Bowl last year, this declaration cannot be defended.

In their study, patients with MODERATE achilles tendinopathy did not do better with PRP compared to saline controls.  All patients received eccentric strengthening exercises.  Their data does support the conclusion that PRP is not better than saline but ONLY for moderate tendinopathy (as measured clinically, no imaging data was reported) at six months of follow up.    The authors stated they will be following those patients for a year.  If for some reason, the PRP patients continue to improve and the saline ones do not, there could be a difference at one year.  However, the conclusion could then only be made that PRP works for MODERATE achilles tendinopathy not any other clinical entity.  Patients with SEVERE tendinopathy that has failed eccentric training was not tested in this study.

The authors need to be recognized for completing this study as we need more level one evidence like it to best define how to use PRP.  Soon, we will have more published literature to discuss. 

We still need to define the optimal formulation and dosage of PRP.  No data was collected on the patients with regard to what was actually put into the patient in terms of total platelet concentration and or white blood cell concentration.  Importantly, we also need a better understanding of the mechanisms behind PRP.