May
01
2021

The Power of a Placebo

By | chronic pain, fractures, Pain, wound healing

A publication in Nature Communications investigated the power of a placebo. Specifically, they wanted to know whether there is a difference between a hidden and a known placebo. With a hidden placebo the patient is unaware whether a pill is a placebo pill or a real medication. With a non-deceptive or known placebo, the patient knows it is a placebo. In this study the investigators wanted to know whether a non-deceptive placebo still can have an effect. As we shall see below the answer is: yes, non-deceptive placebos still have an effect. This was also summarized in this review.

Literature review

The authors reviewed the literature about placebo effects. They found 26 studies that reported positive effects with placebos, but they were mostly self-reporting. However, 8 studies measured objective markers. Only one study found improvement with a placebo therapy, namely by performing a task. The researchers also learnt that physical conditions do not respond to a placebo therapy. Examples of such physical conditions are wound healing, healing of fractures or appendicitis requiring surgery. In contrast, the conditions responding to either hidden placebo or non-deceptive placebo involved emotional distress. This was what the subsequent experiments concentrated on.

The experiments

62 men and women participated in experiment 1. Experiment 2 had a nonclinical sample from another large university in the Midwest.  Only females were accepted for experiment 2. The investigators wanted no sex differences in brain structure, brain formation and emotion processing.

The first experiment

For the first experiment the researchers recruited 62 healthy male and female students between the ages of 18 and 30. They were from two universities, namely the Michigan State University and the University of Michigan. Before the experiment started the hidden placebo group read an article about pain treatment. They were also given nasal placebo drops with the remark that this would help making the measurements more accurate. The known placebo group read another article that explained how placebos work. The text included a passage that explained that placebos work even in the case where the person knew they were a placebo. The same nasal drops were given with the remark that there was no active ingredient in it, but it “would help reduce their negative emotional reactions to viewing distressing images if they believed it would. “

Results of first experiment

The researchers asked participants to view a series of 20 images with negative and cruel content. The subjects also viewed 10 images that were neutral in content. The participants viewed each image for a few seconds, then the investigators asked how they felt on a scale of 1-9. The group who knew that the nasal spray was a placebo felt less negative after viewing the distressing images compared to the other group.

The second experiment

In the second experiment the researchers showed a mixed sequence of neutral and distressing images to female subjects. The purpose was to measure the brain activity as a result of invoking various feelings. The investigators employed a modified continuous electroencephalography (EEG) recording of the brain activity to measure the processing of feelings. They showed a neutral screen between the negative and neutral images and asked the participants to clear their mind. The researchers scanned the brain activity at two time points. The first point measured the patient’s immediate reaction. The second point measured the brain activity at the end of emotional processing and understanding of the image. As discussed below this experiment showed the power of the placebo.

Results of the second experiment

There was no difference of the known placebo group and the control group (the deceptive placebo group) with regard to the initial reaction to the images. However, the placebo group showed less activity in the second period. The researchers monitored the brain activity with a modified EEG and in comparison to the control group. According to the authors the known placebo group was able to process their emotional response to the distress better than the control group.

The authors attempted to correct for confounding variables.  In the process they found out that those who did not believe in the power of a placebo still reacted the same way as the placebo group did. The researchers performed the second experiment only on women as the brains and processing modes are sex-specific. They did not want to introduce confounding variables unwittingly. At this point we do not know how males as a group react in similar experiments.

"The

Conclusion

With a hidden placebo the patient is unaware whether a pill is a placebo pill or a real medication. With a non-deceptive or known placebo, the patient knows it is a placebo. In a study with two experiments the investigators wanted to know whether a non-deceptive placebo still can have an effect. The result of the experiments showed that non-deceptive placebos still have an effect. The proof for his was with placebo nasal drops. The subjects viewed 20 upsetting images and subsequently 10 neutral images. They scored on a scale of 1-9 how upset they felt about the distressing images. The group who knew that the nasal spray was a placebo felt less negative after viewing the distressing images in comparison to the other group.

Placebo helps to process emotional response better than control group

In the second experiment investigators employed a modified continuous electroencephalography (EEG) recording of the brain activity to measure the processing of feelings. The investigators showed alternating upsetting images and neutral images to a female group of students. According to the authors the non-deceptive placebo group was able to process their emotional response to the distress better than the control group. This showed the power of the placebo. The authors concluded that these results may help develop new treatment plans for depression, emotional disorders and emotional distress.

Jan
05
2019

Health Benefits of Vitamin E Tocotrienols

By | Cardiovascular disease, Diabetes, fish oil, food, heart attack, Heart Disease, omega-3 fatty acids, Skin Disorders, Stroke, wound healing

Dr. Barrie Tan gave a talk about health benefits of vitamin E tocotrienols that I attended. This occurred at the 26th Anti-Aging Conference of the American Academy of Anti-Aging Medicine in Las Vegas (Dec. 13-15, 2018).

First of all, Dr. Tan stressed that there has been some confusion about vitamin E, as in the past the school of thought was that the main active ingredient of vitamin E would be alpha-tocopherol. Furthermore, many clinical trials with this ingredient go back to the 1960’s, which showed antioxidant activity. But further research revealed that there were many other tocopherols and isomers of tocotrienols. What is worse is that beneficial cardiovascular effects of the newer tocotrienols became null and void through traces of alpha-tocopherol in the mix.

Finally, this led to purer vitamin E production without alpha-tocopherol contamination. Recent clinical trials found that health benefits of vitamin E tocotrienols are linked to delta- and gamma-tocotrienols. They were many times more active in preventing heart attacks and strokes than former mixes of vitamin E.

Annatto derived tocotrienol

In 2002 scientists were able to extract pure tocotrienol without contamination of alpha-tocopherol from annatto. Prior to this vitamin E came from rice and the red palm fruit. But rice contained 50% of tocopherols, while the red palm fruit contained 25% of it.

Here are several sources of vitamin E. The components of tocopherols and tocotrienols vary depending on the source as follows.

Rice: 50% tocopherols (inactive or antagonistic), 15% alpha- and beta-tocotrienols (less active); 35% delta- and gamma-tocotrienols (most active).

Red palm fruit oil: 25% tocopherols, 25% alpha- and beta-tocotrienols, 50% delta- and gamma-tocotrienols.

Annatto: 90% delta tocotrienols and 10% gamma-tocotrienols.

Subsequent research was able to discern between the detrimental effect of alpha-tocopherol and the protecting effect of delta- and gamma-tocotrienols. Now the recommendation of Dr. Tan is to use only annatto-derived vitamin E to prevent heart attacks and strokes. He called annatto-derived vitamin E the vitamin E for the 21st century.

Tocopherol interfering with action of tocotrienols

Dr. Tan explained that alpha-tocopherol blocks absorption of tocotrienols from the gut. It also prevents storage of tocotrienols in liver and fatty tissue. By itself alpha-tocopherol leads to premature elimination of prescription drugs. It also increases blood pressure and cholesterol. What is worse is that alpha-tocopherol increases the risk of prostate cancer and glioblastoma in humans. It also decreases bone mass and increases LDL oxidation, which leads to accelerated hardening of the arteries.

Action of tocotrienols

In contrast to tocopherols, tocotrienols (particularly the delta and gamma isomers) have all the attributes that you want from vitamin E. It has the highest anti-oxidant properties among the tocotrienols. Delta- and gamma-tocotrienols accumulate in LDL cholesterol and in lipid-rich organs like the brain, heart, kidneys, lungs, spleen and skin. Abdominal adipose tissue from obesity also stores delta- and gamma-tocotrienols.

Tocotrienol’s antioxidant activity

When you use a vitamin E preparation consisting of only delta- and gamma-tocotrienols, the portion of vitamin E contained in cell membranes protects against oxidation. Vitamin E  also protects lipids from omega-3 supplements and lipids in foods and beverages from oxidation. Tocotrienols are about 50-fold more potent as antioxidants compared to tocopherols. Based on this information it is not by chance that the following statistics were the results of clinical trials.

Cholesterol lowering effect of vitamin E delta- and gamma-tocotrienols

Dr. Tan cited a 6-week placebo controlled clinical study where the anti-oxidant power was measured in terms of reduction of LDL and total cholesterol.

A group of elderly patients were divided into a subgroup that had normal levels of cholesterol and another subgroup with elevated lipid levels. After 6 weeks of taking a vitamin E preparation consisting of 90% delta tocotrienols and 10% gamma-tocotrienols the blood levels dropped as follows.

Hypercholesterolemic group:    LDL cholesterol    Triglycerides       CRP

                                                          20-28%                11-18%         31-48%

In healthy elderly patients the CRP still dropped 21-29%. Gamma-glutamyl transferase, a predictor for heart attacks dropped by 14-20%.

Another study on postmenopausal women for 12 weeks also showed beneficial effects of tocotrienols.

Hardening of arteries

Dr. Tan explained that hardening of arteries is due to a combination of factors. It is due to combined chronic inflammation and deposits of LDL cholesterol in the wall of the arteries. Studies have shown that monocyte adherence is the first step in fatty streak formation in arteries. Delta-tocotrienol is 60 times more powerful than alpha-tocopherol in inhibiting monocyte adherence. Gamma-tocotrienol is 30 times more powerful than alpha-tocopherol. This proves that taking a vitamin E preparation of 90% delta tocotrienols and 10% gamma-tocotrienols is the most advantageous vitamin E combination to take.

Health benefits of vitamin E tocotrienols include hardening of carotid artery

A 4-year study examined the effect of taking 240mg of tocotrienol-tocopherol supplementation. 88% of patients who took the vitamin E supplement showed improvement (regression of the carotid artery stenosis). Placebo patients deteriorated 60%, only 8% improved. In the 4th year of the study total cholesterol decreased by 14% and LDL cholesterol fell by 21%.

Health benefits of vitamin E tocotrienols include type 2 diabetes

Patients with type 2 diabetes received tocotrienols. Within 60 days of taking 250 mg of tocotrienols the serum total lipids were reduced by 23% and total cholesterol by 30%. The LDL cholesterol was reduced by 42%. Triglycerides were also lowered by 15-20%. C-reactive protein (CRP), a marker for inflammation was lowered between 35-60%.

Beneficial effects of tocotrienols on the eyes and skin

Tocotrienols have antioxidant effects on the eyes and skin. With regard to eye diseases glaucoma and cataracts are improving and macular degeneration in diabetics is responding as well.

The subcutaneous fatty tissue absorb tocotrienols well. Delta- and gamma-tocotrienol largely neutralize oxidative stress from UV light and ozone.

Non-alcoholic fatty liver disease (NAFLD)

This condition has a close association with obesity and the metabolic syndrome. The liver stores excessive fats. About 30-40% of US adults suffer from this disease. Researchers conducted a 12-week study with 71 NAFLD patients. It was randomized, double blind and placebo-controlled. After 12 weeks of supplementation with delta- and gamma-tocotrienol there was evidence of reduction of stress on the liver by improved liver enzymes. The ALT and AST enzymes were reduced by 15-16%. There was also an 11% reduction of triglycerides and 18% lowering of CRP, which indicates a reduction of inflammation. The fatty liver index score showed a decrease of 11%. This suggests that there was intrahepatic fat reduction. The group with delta- and gamma-tocotrienol supplements lost on average 9.7 pounds. Here is another study regarding non-alcoholic fatty liver disease and using tocotrienols.

Health Benefits of Vitamin E Tocotrienols

Health Benefits of Vitamin E Tocotrienols

Conclusion

Vitamin E supplementation is undergoing rejuvenation after research has established that it is delta- and gamma-tocotrienol that are the active antioxidants among the 10 or so tocopherol and tocotrienol isomers. The most active of them, delta- and gamma-tocotrienol, have excellent absorption in the gut and migrate through the blood stream to the lipid rich cells in the body. Key organs like the brain, heart, kidneys, lungs, spleen and skin accumulate vitamin E. Even the abdominal adipose tissue takes up vitamin E, which is beneficial when a person becomes obese or develops diabetes. Apart from lowering triglycerides, total and LDL cholesterol, vitamin E (delta- and gamma-tocotrienol) is also important for directly interfering with hardening of the arteries.

Vitamin E protecting skin, eyes and liver

Vitamin E also protects the skin and eyes against UV light. There can be a partial reversal of tissue damages. Finally, I pointed out that vitamin E can reverse non-alcoholic fatty liver disease (NAFLD). It is important to leave out alpha-tocopherol, which is an older form of vitamin E that is cheaper to produce, but will interfere with the function of delta- and gamma-tocotrienol as explained. As I mentioned earlier, various vitamin E supplements are on the market. It is obvious that they are not equally beneficial.

I recommend you take about 125 mg of vitamin E in the form of delta- and gamma-tocotrienol every day. I take Annatto tocotrienols (Cardiovascular Research Ltd.) 1 softgel daily.

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Feb
27
2016

Orthopedics Without A Knife

By | Arthritis, Orthopedics, Pain, regenerative medicine, scar tissue, stem cells, wound healing

Dr. Fields gave a talk in Las Vegas about orthopedics without a knife. His talk took place at the 23rd Annual World Congress on Anti-Aging Medicine on Dec. 12, 2015 in Las Vegas. Dr. Fields gave a talk entitled “Regenerative orthopedics – non-surgical repair with stem cells/PRP/prolotherapy”. In essence the talk was about alternative treatments to surgeries in orthopedic medicine.

Dr. Peter Fields, MD, DC is a board certified medical physician and chiropractor. He is also the director of the Pacific Prolotherapy & Medical Wellness Center in Santa Monica, CA.

Introduction

Joints, muscles, tendons, ligaments and joint capsules control the movements in joints. Due to injuries and wear and tear these body parts can have a lack of function, which will lead to pain and disorders. The result can be weak, torn or damaged ligaments and tendons, arthritic changes, excessive joint motion, increased pressure, and a decrease in range of motion.

This is the common treatment cycle in medicine

Joint pain prompts you to see the doctor. You are told it is arthritis, and you get non-steroidal anti-inflammatories (NSAID’s). You come back with more pain, and you’ll get a stronger NSAID prescription. Eventually a cortisone injection is given, which helps for a few months, but then the pain reoccurs. The doctor arranges for an MRI scan. A referral to an orthopedic surgeon is likely to be the next step, and an arthroscopy (pinhole surgery) is arranged. In that case, if this does not resolve the pain, surgery like a knee replacement or hip replacement is suggested.

Common sayings when traditional medicine has nothing to offer

You may have heard some of these common sayings before. “Nothing more we can do about it!” -“I suggest you learn to live with it”- “You should never play that sport again!”- “Take these pain medications” and “The only alternative is surgery!”

The problem is, that none of these pieces of advice are really helpful. This type of approach does not treat the cause; it is directed against symptoms.

How to treat the cause?

Prolotherapy

Prolotherapy is a natural, non-surgical method to assist the body to heal torn soft tissues. It works in cases like torn ligaments, damaged tendons, cartilage, menisci or a torn labrum in the shoulder. Hyperosmolar dextrose solution is injected into the injured area. This stimulates the body’s healing forces and the body repairs what is damaged. More information is found here. In essence, prolotherapy fixes the cause, not just the effect; it heals, and it is permanent. Prolotherapy strengthens tissues, relieves pain and increases the range of motion in joints. There is 80 to 85% full pain relief and more than 80% improvement in range of motion. Prolotherapy promotes the healing of torn or damaged ligaments and tendons.

Conditions suitable for treatment with prolotherapy

Suitable conditions for treatment with prolotherapy are sports injuries, muscle tears, arthritis, tendinitis, bursitis, sciatica, TMJ problems, and fibromyalgia. Common areas treated with prolotherapy are the hip, knee, shoulder, ankle, neck, lower back and elbow. Dr. Fields showed MRI scans before and after prolotherapy treatments of ligament injuries within the knee and of shoulder ligament tears before and after treatment. Normally the physician expected these injuries to require surgery. But all that was done was one or two injections (prolotherapy treatments) with reactivation of the affected joint. There were astonishing results shown with MRI’s before and after herniated disc injuries and how they healed in a relatively short time following prolotherapy.

PRP prolotherapy

Platelet rich plasma (PRP) is a tool from regenerative medicine to amplify the healing response in connection with stem cell therapies .  The lab technician takes blood from the patient and subsequently spins it down in a centrifuge. The platelet rich fraction (PRP) contains all of the growth factors, which have the healing power of the blood. The physicians combines this with prolotherapy to make healing even more successful. This is particularly useful for labral tears in shoulders, meniscus tears in knees and other localized injuries.

Stem cell prolotherapy

Stem cell therapy has been the gold standard for repairing more serious problems. Dr. Fields combines stem cell therapy with prolotherapy to treat more serious injuries like end stage arthritis.  This is the case when bone rubs on bone, where conventional orthopedic medicine would offer a joint replacement in the hip or knee. Stem cell prolotherapy can repair any joint that has cartilage damage. A severe meniscus tear in a knee or a severe labrum tear in a shoulder would also be situations where stem cell prolotherapy is superior to surgery or to just using prolotherapy alone.

Here is a description of the procedure

Before the patient’s procedure the physician first harvests bone marrow stem cells by way of a pelvic bone aspirate; secondly the physician obtains mesenchymal stem cells from fatty tissue by aspiration of abdominal fat. A cell separator provides the stem cell fractions. The physician combines both types of stem cells, the bone marrow stem cells and the mesenchymal stem cells from fat as each one has its own strengths. These two stem cell types are more effective in combination to repair whatever tissue needs repair. Thirdly, the lab technician will draw blood from the patient to obtain PRP, which contains the growth factors needed to activate the stem cells to do their job of healing. The last step is that the physician now combines hyperosmolar dextrose (the prolotherapy part) with the stem cell preparation and mixed in PRP and injects this mixture into the injured area.

Conditions that respond to stem cell prolotherapy

This procedure has superior healing power. Before and after MRI scans of all of the major body regions showed impressive results. Several video recorded testimonials  complemented the MRI scans. It is surprising how quickly and completely fairly severe injuries can heal using stem cell prolotherapy. One particularly nasty condition is osteonecrosis of the hip, which can occur as a side effect of chronic cortisone treatment for arthritis, asthma or chronic obstructive lung disease. One or two stem cell prolotherapy treatments will heal this condition because the stem cells build up brand new bone and get rid of the old necrotic bone from the osteonecrosis. Conventional medicine has no answer for this condition. Regenerative orthopedics is successful by using stem cell prolotherapy.

What are the advantages of regenerative orthopedics?

Regenerative orthopedics reduces pain very quickly and it improves function rapidly. Healing occurs naturally, and it strengthens the tissues involved. Particularly complicated lower back pains or lower neck pains (due to degenerative disc disease, facet joint osteoarthritis, spondylolisthesis and significant foraminal stenosis) respond really well to stem cell prolotherapy, getting rid of chronic pain. The speaker showed before and after MRI scans. He also shared testimonials from patients about the various procedures.

End result following stem cell prolotherapy versus conventional surgery

This is quite in contrast to what conventional orthopedics has to offer: discectomy with fusion surgery, where the patient often has scar pain later. With a laminectomy to treat a foraminal stenosis the patient may have limited improvement of the chronic back pain for a couple of months, only to experience new back pain from a subsequent spinal stenosis as a late complication from the prior surgery. The end result with conventional orthopedics is disability, pain and suffering; the end result with regenerative orthopedics is a patient that is well, active, pain free and thankful.

Orthopedics Without A Knife

Orthopedics Without A Knife

Conclusion

There is a form of orthopedics without a knife: regenerative orthopedics. The tools are prolotherapy for minor musculoskeletal problems. Some very conservatively minded physicians still scoff at this, but wrongly so. PRP prolotherapy is suitable for more severe injuries that require more healing power. Stem cell prolotherapy is what the physician uses for the severe cases. All of the healing power (minus the knife) is put to use. Two types of stem cells initiate healing where there is a need for it. The stem cells transform into the cell types that do the repair.

Two types of stem cells needed sometimes

Research has shown in the past that the mesenchymal stem cells alone will not heal cartilage of joints very well, but in combination with bone marrow derived stem cells this heals quite well and efficiently. Healing osteonecrosis and complicated lower neck and lower back problems borders to miraculous healing. Regenerative orthopedics is definitely something to remember should you get into trouble down the road. There are alternatives to the knife!

Oct
10
2015

Tissue Repair With Extra Cellular Matrix

By | extra cellular matrix, regenerative medicine, scar tissue, wound healing

Are you ready to learn about futuristic medicine consisting of tissue repair with extra cellular matrix? On September 5, 2015 I watched an interesting documentary on Discovery Channel while working out on the treadmill in the gym. This gave me the idea that this would be good material for a blog. After a little research on the Internet I found the full extra cellular matrix story, which you can read about below.

An amputated finger grows back

Lee Spievak, a man who loves flying model aircraft had an injury to his his right middle finger. A rotating model airplane propeller chopped off the end of his right middle finger. His surgeon felt that there was nothing much that could be done. But his brother who works in regenerative medicine knew about a powder made from pig’s bladder tissue, which Dr Stephen Badylak from the University of Pittsburgh, had pioneered. His brother sent a sample of powder (extra cellular matrix, ECM) to Lee Spievak who sprinkled some on the open wound (the stump).

New tissue forming with extra cellular matrix powder

Within two applications he saw that new tissue was forming. In a matter of 4 weeks it sealed up, the wound and a new finger grew to the same length as before. In the course of 4 months his nail, skin, his feeling and even his fingerprint were back to normal.

This story happened in Cincinnati in 2005. In this news story it is explained why the ECM powder worked so well: it prevented the wound from closing and it stimulated the body to heal.

A large thigh muscle defect grows back

Marine Sergeant Ron Strang was severely wounded by a roadside bomb in Afghanistan where a large part of his left quadriceps muscle (left thigh) was ripped off. After several surgeries the surgeons decided that Ron was a good candidate for part of a trial that is ongoing involving about 80 Veterans with similar injuries. Dr. Steven Badylak from the University of Pittsburgh suggested with the next surgery to put extra cellular matrix from pig bladder into the remaining quadriceps muscle to see whether it would regrow part of it.

Surgery with addition of extra cellular matrix from pig’s bladder

The surgery followed by physical exercise was so successful that Sergeant Strang is now able to run and do all the activities he wants. There is still a scar, but in comparison to the initial injury where a big chunk of muscle was missing, the remaining scar was insignificant.

Dr. Badylak explains in the video of the link that the insertion of the sheet of extracellular matrix immediately recruits the patient’s own stem cells, which makes new muscle cells, new nerve tissue, new skin, whatever the body needs to heal what’s missing in the injured area.

Dog gut growing into a dog aorta

Dr. Badylak from the University of Pittsburgh had a veterinary medicine degree before he studied medicine and became a surgeon. From the beginning his interest was in regenerative medicine.

After he saw the success with Lee Spievak’s finger regeneration, he thought that there must be a way to regenerate other tissues. He started doing experiments on dogs where he removed part the arch of the aorta and replaced it with a piece of gut from the same dog to see whether the dog would survive and whether the gut would be strong enough to withstand the pressure from the outflowing blood in the aorta. He figured that the tubular structure of the gut would be a better template than the synthetic aorta pieces that are still in use by thoracic surgeons. To his surprise the first dog (his own dog named Rocky) survived and did well.

Dog experiments to understand how extra cellular matrix works

He accumulated data on a total of 15 dogs. All of them survived and did well. He could not understand what had happened, so he reexamined one of these dogs where he got histological samples and analyzed them under the microscope to see what was going on. What he expected was the typical findings of the gut transplant, but instead he found a new aorta with all of the histological findings of aortic tissue. There was a transformation of a piece of gut into aortic tissue!

Next Dr. Badylak repeated the surgical procedure, but this time he inserted a piece of gut from a cat, removed the lining of it (the mucosa) and the muscle layer, (the muscularis),. The remainder was only the extra cellular matrix, a thin tubular structure of ECM.

Aorta scaffolding made of extra cellular matrix survives in dogs

When he was done, he was wondering whether the body would reject the catgut ECM. After all, it came from another species. Normally with whole organ transplants one can expect rejection of the foreign tissue. None of that happened. The experiment went flawlessly: the transplant survived like all the others and again the ECM had turned into dog aorta. It was possible to integrate the extra cellular matrix into the aorta without any scar formation! None of this fitted any conventional medicine model; it was the blueprint for the regenerative medicine model.

Dr. Badylak recognized that this was a huge step forward, and he would need easy access to ECM material. He got it from the pig slaughterhouses dotting the Indiana countryside surrounding Purdue. There would never be a shortage of tissue for preparing the scaffolding of the ECM for various applications.

Repair of tissue defects with extra cellular matrix in various body regions successful

By now the surgeon had proven that the gut or ECM transplant was switching off an inflammatory reaction, which suppressed scar formation, and simultaneously promoted regeneration. But the missing puzzle still was how the body generated the aortic tissue.

Dr. Badylak tested whether the procedure would work for large veins, smaller arteries and Achilles tendons.  He did this all in dogs and using pig’s ECM. The answer was it worked all beautifully with no scarring and perfect healing results. Control dogs did not get the ECM, but were only operated on and then repaired conventionally in their Achilles tendons.  They developed a limp from scar tissue. This is what often happens in humans as well with conventional surgery. But none of the dogs that had 3 cm cuts and then received a treatment with pig’s ECM developed a limp or scarring. They healed perfectly.

Large company supports Dr. Badylak’s work

In 1992 DePuy licensed Badylak’s ECM-derived “biologic scaffolds” for all orthopedic applications. DePuy is a big company that makes supplies for hip and knee replacements and much more. This was an ideal support for Dr. Badylak’s work.

In 1999 the FDA approved pig’s bladder ECM for human applications. This included the use of pig’s ECM for shoulder rotator cuff tears in patients. The FDA also approved it for abdominal hernias and for esophageal reflux damage. In addition the FDA approved it to induce the regrowth of the outer lining of the brain following brain surgery.

He could now continue his research and find out what the missing puzzle was.  How did the body use the pig’s ECM and repair tissues?

Stem cell recruitment by ECM

Dr. Badylak was visiting a colleague of his in Los Angeles, Dr. John Itamur who had previously repaired a rotator cuff tear on a patient 8 weeks earlier using porcine ECM. The same patient had an unrelated shoulder injury. This required surgery just adjacent to the previously repaired rotator cuff. The surgeon decided to take a small biopsy to see how the healing tissue looked. This was when Dr. Badylak came for a visit. The microscope showed a surprise: the scaffolding had disappeared as expected. But there were a lot of new cells there. They did not look like inflammatory cells, muscle cells or nerve cells; they were stem cells. Dr. Badylak read several papers that told him that ECM breaks down into so-called crypteins. These peptides have powerful stem cell recruiting properties.

Experiment show how extra cellular matrix recruits stem cells 

In 2003 he started groundbreaking experiments in mice that proved this theory to be correct. He X-rayed a group of mice to kill all of their bone marrow stem cells. Then he injected stem cells tagged with a fluorescent marker. They repopulated the bone marrow with these tagged stem cells from the same strain of mice. Now he removed a piece from the Achilles tendon and repaired the defect with pig ECM. Stem cells tagged with a fluorescent marker were flooding the Achilles tendon repair area. Even months after the Achilles tendon repair with ECM the new Achilles tendon was still filled with some of these tagged cells showing that some of them had matured into regenerated tissue.

Video showing would healing with extra cellular matrix and the final outcome of dog Rocky

Here is a link that contains a video about Sergeant Strang and his severe leg injury (repair of a rectus muscle tear). You may wonder how Rocky, the initial dog did who had an aortic segment replaced by a piece of gut. Rocky lived for another 8 years and was healthy until the very end.

Tissue Repair With Extra Cellular Matrix

Tissue Repair With Extra Cellular Matrix

Conclusion

You saw how the observation of a healing finger turned into experiments on dogs. Aortic defects and Achilles tendon defects healed without scarring. You learnt how pig’s or cat’s ECM were in use as scaffolds and that the body absorbed this. They recruit stem cells from the host’s body that subsequently do the healing. The exciting news about ECM is that it promotes healing, recruits stem cells, but also suppresses inflammation and scar formation.

We already hear that ECM is used in hernia repairs, rotator cuff repairs for shoulder injuries, and also in hair transplants, where Acell material is mixed in to improve the transplant success.

It is being used in lower esophagus surgery in cancer cases and with reflux esophagitis.

What will be the next application for ECM? We do not know everything, but it is a promising step into the future of regenerative medicine!