The Power to Heal Comes from Within

Powerful chemical weapons, also known as drugs, and sophisticated surgical procedures have dominated the practice of medicine for many decades.  For at least the last 15 years, maverick researchers and physicians have been exploring biologic alternatives to drugs and surgery.  Instead of searching the world for a novel chemical compound or engineering a sleek surgical device, they have looked in an unusual place--inside the body itself.  Could it be possible that the power to heal comes from within our own bodies?  The answer today is a qualified yes.  

Think about it for just a moment.  Next time your get a small paper cut, simply observe what happens.  You bleed a little.  It stops on it own.  You put a bandaid on it and magically it heals over the course of less than a week.  Similarly, if you sustain a simple fracture, it typically heals on its own with immobilization and a few weeks of time.  Your liver is your most amazing regenerative organ.  You can literally cut out a lobe of your liver and transplant it into someone else.  That missing lobe will then regrow on its own.  Skin, bone and liver are tissues that have excellent capacity to self heal. Other tissues need a helping hand.  Fortunately, within our own bodies are many tissues that can help heal other tissues.  Blood, bone marrow and adipose tissue (also known as Fat) are three examples.

To begin, let's explore platelet rich plasma, also known as "PRP".  PRP is a component of blood that can be prepared using a simple desktop sized centrifuge in about 10 minutes.  I have using PRP to treat chronic tennis elbow now for more than a decade with excellent success rates.  Multiple studies now confirm the value of PRP in the treatment of this common disorder.  A recent meta-analysis of randomized controlled trials noted PRP to be "of great clinical significance."  PRP has also been used to treat diabetic foot ulcers, knee arthritis and degenerative disc disease.  Overall, there are now more than 8600 published studies evaluating the basic science and clinically efficacy of PRP.   Importantly, in all of the areas studied, PRP has an excellent safety record.  That of course makes sense.  PRP is simply a component of your own blood.

Cancer immunotherapy is another example of using your body to help heal itself.  Cancer immunotherapy essentially reprograms your immune system to help fight nasty cancers.  Recently published data has found an "unprecedented" 94% of patients with a specific type of blood cancer achieving complete resolution of their symptoms.  The technique involves removing your own white blood cells, reprogramming them to attack tumors in the lab and then injecting them back into your body.  To quote one researcher, "This is really a revolution."

Finally, a therapy that sounds like it came out of a science fiction or horror movie is just beginning.  The idea of parabiosis involves merging the circulation of two animals.  The original research was done in young and old rats in 1956.  For the details please review a tantalizing paper entitled "Experimental Prolongation of the Life Span (Ref 1)  When their circulations were connected, the young mice started becoming "old" and the old mice started to appear "young".  Something in the blood of young mice was helping reverse the affects of aging in older mice.  The coats of the old gray mice were turning brown again.  Other research conducted at Stanford suggested young blood could boost brain cell growth in older mice.  (Ref 2, Ref 3 Ref 4)  This research was so intriguing, it led to the development of a clinical trial focused on the transfusion of young blood to older patients with Alzheimer's disease.   Silicon Valley tycoons are also helping finance similar "treatments" for middle aged rich people who want to stay young or reverse the affects of aging.  A company has even been started and is presently conducting clinical trials.  Interestingly, the company is named Ambrosia after the mythologic Greek drink that was supposed to confer longevity or even immortality.  Peter Thiel, an iconoclastic venture capitalist , appears to be quite interested in this approach to combating the aging process.  This approach is clearly not yet proven but is intriguing.

If we are seeking transformative solutions to difficult problems, I suggest we look inside.  We might just find the power to heal.

Allan Mishra

Will Biologics Revolutionize Musculoskeletal Care?

The economic costs of musculoskeletal care in the United States is approaching $800 billion or about 5.7% of annual GDP.  (Ref)  These costs are expected to increase significantly as our population ages.  This is clearly not a sustainable path.  A recent article published by the American Academy of Orthopedic Surgeons (AAOS) suggests the "early evidence is promising" for biologics to revolutionize musculoskeletal care.  (AAOS Article in full)

Biologic therapies represent a rapidly evolving frontier similar to arthroscopy in the 1970s and 1980s.  There will always be a need for continued research and development but the data supporting treatments such as platelet rich plasma (PRP) and stem cell treatments for tendinopathy and arthritis is increasing significantly.  PRP is now a recognized treatment for chronic tennis elbow that has been shown to be better than surgery.  (See Ref)  The number of PRP articles on PubMed now is over 8000 and the Google Trends for PRP is rising rapidly. (See Graph)

Biologic orthopedic procedures are in the process of revolutionizing the options available for patients for difficult problems such as arthritis.  It is an exciting time to execute on these point-of-care biologic treatments.   Continued progress will demand hard work and innovation by elite motivated teams in order to produce transformative outcomes for patients.


AM
TotalTendon

$87 Billion Dollars for Total Knee Replacements by 2030?

We have an epidemic of knee arthritis in the United States with over 10 million affected Americans (Ref).  Many treatments are prescribed with variable efficacy for this common problem.  When all else fails, knee replacement is often recommended.  This procedure is overall highly successful but also expensive.

In 2009, the CDC reported the estimated costs of knee replacement in the US to be $28.5 billion dollars (Ref).  Published reports suggest there will be a need for almost 3.5 million knee replacements in the United States by 2030 (See paper).  At a conservative total cost of $25,000 per surgery, that translates into $87 billion dollars. So, the projections suggest the costs will triple over the next 15 years.

That is $87 Billion Dollars just in the United States to treat end-stage knee arthritis.  That is just the cost of knee replacements.  It does not include other surgical or non-operative costs.  It also doesn't include treatment of other potentially arthritic joints such as the hip or shoulder.

We can and should immediately begin an all-in assault against arthritis.

Patients need to act on the first line of treatment.  They can help themselves with a program of diet and exercise.  Simple exercises such as the QuadCrunch and Hamstring Stretching can be quite helpful.  Riding a bike is another way to exercise with arthritic knees.  Losing even a small amount of weight can result in less pain and more function.

The good news is many new treatments are in development to treat this difficult problem.  The bad news is the effort is fractionated.  It is important to note that knee arthritis is not simply a disease of the cartilage.  There is dysfunction in muscle, tendon, ligament, cartilage and bone when a patient has arthritis.  A better understanding of the genetic and epigenetic causes of arthritis is also needed.  We will need a systematic approach to treating all of the components of the disease in order to be successful.

On the horizon are a plethora of biologic treatments including platelet rich plasma, stem cells and even gene therapy.  We need to embrace these novel treatments do the hard work that is needed to prove their safety and value.

A coalition of patients, providers, payers, researchers and industry need to come together and execute on potential treatments and prevention strategies.  We cannot afford to continue with the status quo and spend almost $90 Billion Dollars on knee replacements in 2030.

Please post your comments or suggestions below.

AM
TotalTendon

Microfracture Surgery Jadaveon Clowney

The Houston Texans' Jadeveon Clowney recently underwent "microfracture" surgery on his ailing right knee.  (See ESPN report)

The report suggests the talented Mr. Clowney will be out for 9 months or more.  Just what is microfracture surgery and why does it take as long to recovery as it does for a baby to born?

Microfracture Surgery

Let's start with the basics.  There are two types of cartilage in the knee.  The surface cartilage which covers the bone.  This is known as articular cartilage and can be thought of a type of cap or covering of the end of the bone.  This cartilage is present in any joint.  In the knee, there is another type of cartilage, the meniscus cartilage.  There are two menisci in the knee--medial (inside) and lateral (outside).  When the surface "articular" cartilage is damaged, the knee can become quite painful especially with loading and twisting.  Think rushing a passer for example.  Similar symptoms can occur when the meniscus is torn.  It is often difficult to distinguish between the two in terms of which one is the pain generator.

Microfracture surgery is an attempt to create a tire patch over a cartilage defect by poking a hole in the end of the bone and creating an access channel to the bone marrow.  The bone marrow then leaks out via the holes that are created and forms a clot which over time can help cover the defect.  It takes time, many months, for this surgery to work because the "patch" needs to mature.  This technique is useful for small defects in the cartilage but hasn't proven to be great for larger defects.  We do not know the size of Mr. Clowney's knee cartilage injury.

Recent evidence suggests that the addition of platelet-rich plasma can enhance microfracture surgery results.  This has been shown in basic science, preclinical and now clinical studies.

This type of surgery at such a young age is clearly not a good sign.  In the long run, he may require further intervention.  Please read the post below for further information about why we need to accelerate our regenerative medicine efforts.  Mr. Clowney is one of tens of millions of people worldwide with symptomatic cartilage damage.  We need to maximize outcomes of today's surgical techniques and develop new procedures to help keep our athletes and patients in the game.

AM

TotalTendon

Will Kobe Bryant go to Japan to Treat his Knee Arthritis?

Japan Accelerates Regenerative Medicine with Regulatory Reforms

Why the United States Must Follow Their Lead

Sign the online petition supporting Regenerative Medicine

Kobe Bryant, an elite professional athlete from the National Basketball Association’s Los Angeles Lakers, has gone to Germany multiple times to be treated with a portion of his own blood for his creaky, arthritic knees.  The reason why he went to Germany is simple.  He wanted to have the best chance to play at the highest level in the NBA and he had exhausted all his options in the United States.  He went there to be treated with a component of his own blood that targets the inflammation associated with knee osteoarthritis.  The treatment he received is not approved here in the United States. 

Will he go to Japan next time to get the most advanced therapy?  That may happen because in November 2014 Japan enacted legislation creating a new pathway that accelerates the approval process for regenerative medicine products.  We here in the United States need to figure out how to best accelerate our own regenerative medicine efforts or continue to watch our elite athletes and other patients seek treatment beyond our shores.  Let’s explore why Japan acted boldly in favor of regenerative medicine. 

A Nobel Prize was awarded to Japanese researcher and former orthopedic surgeon, Dr. Shinya Yamanaka in 2012 for his pioneering work on how to reprogram mature skin cells into pluripotent stem cells.  His potentially life saving work and the national pride associated with it helped Japan become a worldwide leader in stem cell research.  Importantly, Japan has also prospectively pursued and passed legislation that will dramatically stimulate regenerative medicine.  The country took a leap into a bright future last week with the implementation of regulatory reforms directed at accelerating the development of cell-based treatments. 

The new law established a separate pathway for regenerative medicine products apart from traditional drugs and medical devices. The regulations also created a system that fosters faster commercialization of novel biologic products and can lead to time limited approvals for up to seven years.   Post market data analysis will continue to confirm the safety and efficacy of the regenerative medicine products with the potential to revoke approvals. 

The action by the Japanese government creates the proper equilibrium between the need for accelerated approvals for cell based therapies that have established efficacy while ensuring product safety.  The typical phase one, phase two and phase three trials for new drugs are not a proper pathway for cell-based therapies that have highly complex mechanisms of action that may or may not be identified even with elite preclinical models.  Importantly, many cell-based products come directly from a patient’s own body and therefore have a dramatically higher safety profile. 

Americans are screaming for new treatments for a variety of difficult problems such as arthritis, heart disease and diabetes.  Regenerative medicine and especially cell-based treatments have a chance to help treat and potentially cure these problems.  We need to follow the Japanese lead and create similar pathways in the United States.  Last year during a visit to Japan and its PMDA (the equivalent of the FDA), I was staggered by how engaged they were about regenerative medicine and receptive they were to understanding how to bring safe and effective biologic products to their populace.

The United States can learn a great deal from Japan’s enlightened approach to regenerative medicine.  Safety of course should be paramount.  The idea of a conditional, time-limited approval with reimbursement strikes a perfect chord as we seek better treatments for our patients at more affordable prices.  Competition will arise to obtain approvals based on phase two trials that confirm safety and show a solid degree of efficacy.  Importantly, more competition will lead to better options and faster innovation similar to the computer industry over the last several decades. 

We need to also emulate our Silicon Valley technology colleagues and call for a Medical Moore’s Law.  Identify a specific clinical problem, create a novel solution and within five years double the efficacy and decrease the price by fifty percent.  Data analysis via powerful graphical algorithms should assist with new discoveries and also help with better management of many diseases.  

We must seek dramatically higher horizons instead of being satisfied with iterative improvements.  The Japanese government should be congratulated for passing regulatory reform and implementing transformative solutions.  Sooner, not later, we need to find ways to execute our own regulatory reforms here in the United States to help our patients and to remain competitive on the world stage in regenerative medicine.

Perhaps, then Kobe will be treated in California instead of Germany or Japan.

Allan Mishra, MD

TotalTendon


Sign the online petition supporting Regenerative Medicine

Please post any comments or suggestions about how to safely accelerate regenerative medicine.

References

(http://www.nobelprize.org/nobel_prizes/medicine/laureates/2012/yamanaka-facts.html)

Accessed 11/30/14

http://www.pmda.go.jp/english/events/2014taiwan_sympo/14_Keynote1.pdf

Accessed 11/30/14

Why patients are seeking out platelet rich plasma and other biologic treatments.

Platelet rich plasma (PRP) and adult stem cell treatments derived from bone marrow are rapidly evolving into the mainstream of medicine.  As you can see from the chart above, the number of hits for "platelet rich plasma" is rising dramatically.  There are also over 7400 PRP references on PubMed.org.  Let's explore why.

Patients are seeking out less invasive treatments.  When presented with the option of surgery or an office procedure, patients typically will choose the office procedure.  Surgery often carries significant more risk and certainly more cost.

Patients want to return to sports, work or life as quickly as possible.
Botox and Lasik eye surgery provide patients with almost immediate improvement for wrinkles and vision.  Patients now expect other specialities to deliver similar almost instantaneous success.   Elite athletes are especially interested in returning to the highest level of function as quickly as possible.  They have been one of the primary drivers of PRP and other biologic treatments.

Patients are dissatisfied with the surgical treatments we have been offering them.
This is particularly true when it comes to knee arthritis.  Presently, there is very little definitive evidence supporting the use of many common treatments and there is a Grand Canyon size hole in our ability to effectively manage tens of millions of patients.  Biologic therapies will likely fill this void within the next five years.

Patients intuitively understand the regenerative abilities of your own blood and bone marrow.  Evidence is mounting across a several specialties supporting the use of blood and bone marrow to treat a variety of conditions.  A new study will begin this fall evaluating the utility of giving Alzheimer's patients blood transfusions from healthy volunteers under 30.  (Stanford Blood-Alzheimer's study)

Patients are willing to be treated without perfect supporting data.

Patients do not often understand the need for large clinical trials and are impatient with the time and effort it takes to generate meaningful clinical data.  The use of their own blood (PRP) or bone marrow simply make sense to them and they are willing and often eager to try a new treatment instead of undergo surgery.

We are presently scrambling to figure out how to develop, execute and pay for the clinical trials needed to best understand how to utilize biologic orthopedic therapies.  The good news is:  hundreds of clinicians, researchers and medical device professionals are working diligently on dozens of new treatment options.

Please post any comments about why you may think patients and clinicians are using PRP, stem cells or other biologic treatments.

AM   (@BloodCure on Twitter)
TotalTendon

Biologic Orthopedic Society crosses over 2500 Member Mark

The Biologic Orthopedic Society (BOS) is a group of professionals dedicated to the research and development of biologic treatments for musculoskeletal injuries and disorders.  This group has now grown to over 2500 members worldwide.  Much of the group's focus has been on the use of platelet rich plasma, stem cells and bone marrow concentrate (BMC) for tendonitis, arthritis and degenerative spinal disc disease.

The growth of the Biologic Orthopedic Society (BOS) is a testimony to the rapidly rising interest in biologic solutions to difficult musculoskeletal problems.  Significant progress has been made in terms of better published data supporting the use of biologic therapies in the last 2-3 years.  Clearly, more information and research is still needed.  As the group continues to grown, more and more connections are being made.  Ideas and projects are advancing.  All of this should give hope to those patients in search of better treatments.  Many hard working professionals are striving to deliver better biologic options.  

I'll predict within another 5-10 years, we will be staggered by how much will be accomplished.

Thanks to my many colleagues and friends within the BOS for a fantastic journey so far.

If you are a professional working in the area, please consider joining the group.  

Biologic Orthopedic Society

AM

Total Tendon

Fat Stem Cells help Knee Arthritis

Knee Arthritis is a very difficult problem to solve.  Millions of patients suffer daily from this progressive disease state.  A variety of novel biologic therapies are in development.

Stem cells can come from a variety of sources including your own fat.  These cells are known as adipose derived stem cells.  A recent study from Korea suggests there is value using this type of cell for knee arthritis.  Researchers gave patients escalating dose of the cells and found the high dose resulted in improved pain and function scores.  They also found the cartilage defect defect size decreased while the volume of cartilage in the knee increased.

Fat Derived Stem Cells

This data is encouraging and will need to be repeated prior to broad clinical use.  (See abstract below)

For patients with this problem, the horizon is bright with many potential options like stem cells from your own fat.

AM
TotalTendon

Stem Cells. 2014 May;32(5):1254-66. doi: 10.1002/stem.1634.

Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial.

Jo CH1, Lee YG, Shin WH, Kim H, Chai JW, Jeong EC, Kim JE, Shim H, Shin JS, Shin IS, Ra JC, Oh S, Yoon KS.

Author information

Abstract

Mesenchymal stem cells (MSCs) are known to have a potential for articular cartilage regeneration. However, most studies focused on focal cartilage defect through surgical implantation. For the treatment of generalized cartilage loss in osteoarthritis, an alternative delivery strategy would be more appropriate. The purpose of this study was to assess the safety and efficacy of intra-articular injection of autologous adipose tissue derived MSCs (AD-MSCs) for knee osteoarthritis. We enrolled 18 patients with osteoarthritis of the knee and injected AD MSCs into the knee. The phase I study consists of three dose-escalation cohorts; the low-dose (1.0 × 10(7)cells), mid-dose (5.0 × 10(7)), and high-dose (1.0 × 10(8)) group with three patients each. The phase II included nine patients receiving the high-dose. The primary outcomes were the safety and the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) at 6 months. Secondary outcomes included clinical, radiological, arthroscopic, and histological evaluations. There was no treatment-related adverse event. The WOMAC score improved at 6 months after injection in the high-dose group. The size of cartilage defect decreased while the volume of cartilage increased in the medial femoral and tibial condyles of the high-dose group. Arthroscopy showed that the size of cartilage defect decreased in the medial femoral and medial tibial condyles of the high-dose group. Histology demonstrated thick, hyaline-like cartilage regeneration. These results showed that intra-articular injection of 1.0 × 10(8) AD MSCs into the osteoarthritic knee improved function and pain of the knee joint without causing adverse events, and reduced cartilage defects by regeneration of hyaline-like articular cartilage.

Biologic Orthopedic Update from Las Vegas

The TOBI biologic orthopedic meeting this past weekend in Las Vegas was simply outstanding.  Dr. Steve Sampson put together an excellent collection of lectures and then followed by an impressive ultrasound anatomy session by Dr. Jay Smith from the Mayo Clinic.   Hands on injections and bone marrow aspiration in a cadaver lab completed the stellar conference held at the Red Rock Resort.

Las Vegas Red Rock Area

Some highlights of the sessions.  We heard about the use of PRP in soccer players from Dr. Imtiaz Ahmad from London, England, the use of PRP for osteoarthritis from Dr. Brian Cole from Chicago, the use of adipose-derived stem cells for the treatment of knee osteoarthritis from Dr. Yun Choi from South Korea, minimally invasive techniques for articular cartilage damage from Dr. Neil Ghodadra from Los Angeles and the Andrews Institute Experience using Biologics to Accelerate Healing from Dr. Adam Anz.   Lectures about hydrodissection using ultrasound (Dr. Lam, Hong Kong), the current landscape of disc regeneration challenges and promises (Dr. Bae, Los Angeles) and the value of mesenchymal stem cells (Dr. Caplan, Cleveland) were also given.  That was just part of day one of the conference.  Day two included several more interesting and important lectures.  I think there were over 300 attendees and many more following the streaming video (including myself on day one).  In between the lectures, discussions were carried out in the hallways and exhibit area.  Overall, it was a fantastic international event.

The field of biologic orthopedics is exploding.  Worldwide interest in minimally invasive techniques to treat challenging musculoskeletal problems is rising rapidly.  It will still take time, effort and some luck to discover and develop clinically meaningful treatments.  The good news is, progress is definitely being made toward these lofty goals.

AM
TotalTendon

Biologic Orthopedic Conference in Las Vegas (TOBI)

Today in Las Vegas a group of elite clinicians and researchers from around the world have gathered in Las Vegas for the 5th annual TOBI biologic orthopedic conference.  Discussions about platelet rich plasma, stem cells and a variety of other approaches for difficult problems such as arthritis, tendonitis and degenerative disc disease of the back.

Specific data has been presented suggesting various formulations of PRP and stem cells have value in the treatment of knee arthritis.  Clinical trials ongoing.

I'll be speaking at the conference on Saturday morning and will continue to report breaking news from the conference over the next two days.  Follow me on Twitter for real time updates (@BloodCure)

Dr. Steve Sampson has done a great job organizing the event.  Congrats!

AM
TotalTendon

Can Stem Cells Cure Knee Arthritis?

Can Stem Cells Cure Knee Arthritis?

Unfortunately, the answer to that question is not known today.  It is clear, however, that many novel regenerative therapies are emerging to help the tens of millions of patients worldwide that are suffering from knee arthritis.

First, we must explore what type of stem cells could be helpful in the treatment of arthritis.  Stem cells of various types can be obtained from your blood (peripheral derived stem cells), bone marrow (mesenchymal stem cells), fat (adipose derived stem cells), and even from umbilical cord blood.  Studies today are exploring various ways to extract, purify and concentrate many types of stem cells.  The cells can then be injected as a suspension into your knee, used as part of surgical procedure or even injected after an operation.

Microfracture of Damaged Knee Cartilage

One recent study (Vangsness et al 2014) showed how an injection of mesenchymal stem cells could lead to more meniscus tissue after a knee arthroscopy.  24% of the treated group were found to have at least 15% increased meniscal volume.  This is a small amount in only a a quarter of the patients but it does represent a start.  Another study published last year (Saw et al 2013), injected peripheral derived stem cells after a microfracture procedure and noted improvement in the cartilage quality.  Other approaches (Pak et al 2014) use adipose derived stem cells from liposuction in combination with platelet-rich plasma to treat meniscus tears.  Finally, a review (Anderson et al 2013) of potential stem cell therapies for knee cartilage outlines many potential and emerging options.

Also, a variety of procedures also use non-stem cells to treat arthritis of the knee.  One of the oldest is called autologous chondrocyte implantation.  This is where a biopsy of your own cartilage is taken and then grown in a lab.  The expanded cells and then reimplanted into an arthritic lesion of the knee.  Another procedure simply penetrates the bone under the defective cartilage.  This leads to leakage of some of the bone marrow along with your own the stem cells within the marrow into the defect.  This is called microfracture.  Yet another procedure uses juvenile cartilage that is minced and then glued into a arthritic zone of the knee.

It is clear that there are many competing approaches to the use of cells and stem cells to treat knee arthritis.  None have "cured" the problem.   There is, however, an earnest worldwide research effort that will produce clinically meaningful options for clinicians and patients.

Millions worldwide are waiting for that day.

AM
TotalTendon

References
Anderson et al 2013
Saw et al 2013
Vangsness et al 2014
Pak et al 2014

Platelet Rich Plasma, Stem Cells and Biologic Orthopedics on Dr. Radio

On Monday May 12th, I will be on Sirius-XM Doctor Radio (Channel 81, 7 pm EST, 4 pm PST) discussing platelet-rich plasma, stem cells and other biologic orthopedic treatments.  It is an exciting time for this topic because research in these areas has progressed significantly just in the last few months.  Also, patients and payers are demanding less invasive and more effective treatments for difficult problems such as knee osteoarthritis and degenerative disc disease.  So, tune in at 7 pm EST, 4 pm PST on Monday May 12th to learn more about the frontiers of musculoskeletal medicine and surgery.  

AM

TotalTendon

Best Overall Exercise: PowerKnee Bike Program (Knee OA Part 4)

The PowerKnee Bike Program uses an upright exercise bike to work out all of your leg muscles.  It is the best overall exercise for knee pain and arthritis because it can do so much for you without significant impact on the joint.   By simply riding the exercise bike for 30 minutes 3 times per week you can also improve your cardiovascular fitness and burn a bunch of calories.  See the video below for details.

Record the calories you can burn in 30 minutes and compare your results week by week for a month.  If you are consistent in applying the PowerKnee Bike Program you have an excellent chance of decreasing your pain and improving your knee function.

As always, check with your doc before beginning any exercise program.

AM
TotalTendon

Stem Cells from the Rotator Cuff and Biceps Tendon

In a landmark study, Dr. Pietro Randelli and his colleagues found a population of cells within the rotator cuff and biceps tendon with stem cell like "characteristics (ie, they were self-renewing in vitro, clonogenic, and multipotent), as they could be induced to differentiate into different cell types-namely, osteoblasts, adipocytes, and skeletal 

muscle cells."

The full implications of this paper are difficult to predict but this work could enable entirely new approaches to tendon repair within and outside of the shoulder.  The authors should be congratulated on this truly important work.  See the full abstract below for details.

AM
Total Tendon

Am J Sports Med. 2013 Feb 7. [Epub ahead of print]

Isolation and Characterization of 2 New Human Rotator Cuff and Long Head of Biceps Tendon Cells Possessing Stem Cell-Like Self-Renewal and Multipotential Differentiation Capacity.

Randelli P, Conforti E, Piccoli M, Ragone V, Creo P, Cirillo F, Masuzzo P, Tringali C, Cabitza P, Tettamanti G, Gagliano N, Anastasia L.

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Source

IRCCS Policlinico San Donato, San Donato Milanese, Italy.

Abstract

BACKGROUND:Stem cell therapy is expected to offer new alternatives to the traditional therapies of rotator cuff tendon tears. In particular, resident, tissue-specific, adult stem cells seem to have a higher regenerative potential for the tissue where they reside. HYPOTHESIS:Rotator cuff tendon and long head of the biceps tendon possess a resident stem cell population that, when properly stimulated, may be induced to proliferate, thus being potentially usable for tendon regeneration. STUDY DESIGN:Controlled laboratory study. METHODS:Human tendon samples from the supraspinatus and the long head of the biceps were collected during rotator cuff tendon surgeries from 26 patients, washed with phosphate-buffered saline, cut into small pieces, and digested with collagenase type I and dispase. After centrifugation, cell pellets were resuspended in appropriate culture medium and plated. Adherent cells were cultured, phenotypically characterized, and then compared with human bone marrow stromal cells (BMSCs), as an example of adult stem cells, and human dermal fibroblasts, as normal proliferating cells with no stem cell properties. RESULTS:Two new adult stem cell populations from the supraspinatus and long head of the biceps tendons were isolated, characterized, and cultured in vitro. Cells showed adult stem cell characteristics (ie, they were self-renewing in vitro, clonogenic, and multipotent), as they could be induced to differentiate into different cell types-namely, osteoblasts, adipocytes, and skeletal muscle cells. CONCLUSION:This work demonstrated that human rotator cuff tendon stem cells and human long head of the biceps tendon stem cells can be isolated and possess a high regenerative potential, which is comparable with that of BMSCs. Moreover, comparative analysis of the sphingolipid pattern of isolated cells with that of BMSCs and fibroblasts revealed the possibility of using this class of lipids as new possible markers of the cell differentiation status. CLINICAL RELEVANCE:Rotator cuff and long head of the biceps tendons contain a stem cell population that can proliferate in vitro and could constitute an easily accessible stem cell source to develop novel therapies for tendon regeneration.