Platelet and Stem Cell Therapy — Novel Approaches That Can Help Heal Orthopedic Injuries


Orthopedic injuries can be debilitating, and many who seek treatment frequently end up getting surgery. Unfortunately, the side effects from going under the knife are often irreversible. If a mistake is made, you can end up with a permanent, lifelong problem.

Story at-a-glance

  • Surgery is rarely the ideal choice for most orthopedic injuries. One alternative that can be helpful for a wide range of degenerative joint problems and sports injuries is platelet-rich plasma (PRP) and stem cell therapy
  • Stem cells precisely injected can be effective interventions, capable of regenerating damaged tissue. They can even transform destructive cells into helpful repair cells
  • PRP and stem cell therapy are ideally incorporated as part of a comprehensive treatment plan that includes a healthy anti-inflammatory diet, exercise, and other lifestyle factors that can influence inflammation, such as sleep

In my view, surgery is the last resort almost every single time. The practical question though is, what are the realistic alternatives?

James Leiber, a D.O., who is board certified in Neuromusculoskeletal Medicine and Pain Medicine as well as Family Medicine, has worked with the Air Force and was actually a personal physician to the former President Bush and Vice President Dick Cheney.

He’s currently an associate professor of family medicine and osteopathic principles and practice at the Lake Erie College of Osteopathic Medicine in Bradenton, Florida and runs his own practice, New reGeneration Orthopedics of Florida and is the first Florida affiliate of Regenexx.

He has a passion for interventional regenerative orthopedics — a field in which he has many years of experience. In his Florida practice, he uses a number of different stem cell products and techniques, which he discusses in this interview.

Many years ago he became interested in prolotherapy, which has been around since the 1930s, when orthopedists were trying to figure out how to strengthen ligaments without doing surgery.

They discovered that by injecting an irritant solution into damaged tissue, it will release growth factors that help heal and strengthen the area.

In the last decade, medical professionals have begun using platelet-rich plasma (PRP) or stem cells in the same way. Ultrasound is also used, along with other imaging techniques, which allows the doctor to “see” what’s going on inside the tissue. It’s also helpful for pinpointing the exact location for the injections.

The Benefits of Platelets and Stem Cell Therapy

Platelets are an important part of the healing cascade. They’re responsible for blood clotting and are among the “first responders” to any site of an injury. By forming a clot, they stop bleeding.

This process involves the platelets opening up and spilling out the growth factors held inside. These growth factors act as signaling molecules, issuing the instructions needed to call forth resources to repair the damaged tissue. This includes stem cells.

Stem cells are primitive precursors to your cells. They can be thought of as “baby cells,” and are found in high concentrations in your bone marrow and fat tissues. Some also float around in your blood, and in your joints. Dr. Leiber explains:

“When the (stem cells) come to the area, they can turn into the new tissue that’s trying to be repaired. They can also instruct all the other cells on what to do. They become like the foreman.

They can even take a cell that’s trying to destroy the knee, for example, and convert it into a cell that’s trying to repair.

Stem cells are very powerful in their ability to heal. That’s why we use them. We prefer to use someone’s own stem cells, and for many reasons we prefer to use the stem cells that come from the bone marrow rather than the fat.

There are other types of stem cells. You can get stem cells from someone else. Those could come from the fetus or from the fluid around the fetus [or] the umbilicus. All of those things are, first of all, not being done in the United States.

Secondly, we prefer to use someone’s own stem cells. We think that’s really the safest way to go. We like the idea of culture expanding, but we have some restrictions within the United States of being able to do that.”

Common Ailments That May Benefit From Stem Cell Therapy

When you’re young, you have high amounts of platelets and stem cells, which translate into a high level of self-regenerative ability. Children typically heal from injuries rather quickly.

With age, they become less effective, and the wear and tear on your body starts to outpace your body’s ability to repair itself. At some point, you begin to see chronic conditions from overuse, degeneration, and aging.

“We’re able to take the cells that that person has, isolate them, concentrate them, do a few little tricks with them to make them more effective, and then precisely place them in the areas that the tissue has damaged. We can get very good healing even for very advanced conditions.”

Most of Leiber’s patients are active seniors seeking to address age-related degeneration. Many are former competitive athletes. Over the past few years, awareness about PRP and stem cell therapy has also spread among professional athletes seeking treatment for sports injuries. Common complaints include:

  • Knee problems such as arthritis, knee or meniscus tears and anterior cruciate ligament (ACL) tears
  • Shoulder injuries like rotator cuff tears ,arthritis, and labral tears
  • Spine problems, such as disc herniations and spine arthritis
  • Hip, hands, feet, and elbow problems

Using Own Stem Cells Is a Safe Treatment Option

Stem cells can also be clinically indicated for other things, such as regeneration of peripheral nerves, organ damage, and even type 1 diabetes.

“There’s incredible potential for the use of stem cells from either bone marrow or fat for other types of problems, including heart and brain,” Leiber says.

“But we don’t claim to be as experts in that. I think there’s an issue when a doctor treats everything under the sun with stem cells. I think there’s a lack of expertise when that happens.”

One common concern with stem cell therapy is whether the injected stem cells might become malignant. According to Leiber, at least in orthopedic treatments (which is his specialty), stem cells have never turned into anything abnormal, and there’s more than a decade’s worth of patient data to support that claim.

Part of these safety concerns stem from the fact that when you inject another person’s stem cells, or ones from animals, the risk of malignant conversion does exist.

In fact, the veterinarian associated with my site, Dr. Karen Becker, has treated many animals using stem cells, and noticed that many dogs invariably develop cancer a few years down the line after being treated with another animal’s stem cells. This does not appear to be the case when you’re using your own stem cells though.

“We’ve been tracking that for sure,” Leiber says. “When you use someone else’s stem cells, there are other risks associated with it. There’s rejection risk. You’re obtaining the genetic material of someone else. I think that needs to be sorted out. I’m sure over time we can get that to be a safe therapy, but that needs a lot more research.”

What Stem Cell Therapy Is Not

While stem cell therapy has great healing potential, it would be inadvisable to approach it thinking it’s a one-shot magic bullet. On the contrary, it’s ideally incorporated as part of a comprehensive treatment plan that takes other lifestyle factors into account. Leiber explains:

“Stem cells have the capacity to repopulate and regenerate themselves. When we take bone marrow out, for example, they will repopulate themselves in six weeks. We give people about a six- to eight-week window, maybe a little bit longer depending on their situation.

We try and push them in the right direction with a lot of diet and food planning advice, supplement advice, exercise advice, discussions about sleep and environmental chemicals, and a whole bunch of different things to get them as healthy as possible.

Some people are facing a crossroads in their life where they’ve been told by multiple orthopedists that they need a spine fusion or they need a knee replacement, for example, and they really don’t want to go that route. They’re willing to make the changes necessary. I think it’s a real unique opportunity. I have been counseling people in this regard for many years, but the patients I’m seeing now are very, very motivated. We are able to sort of kick-start their life back in a lot of different ways.”

On the whole, your chances of success are radically improved if you eat real food, eliminate processed foods, and focus on high-quality fats while minimizing net carbohydrates (total carbs minus fiber), along with moderate protein. This kind of diet helps upregulate your body’s innate repair and regenerative systems. Most importantly, you radically downregulate inflammation, which is one of the core variables contributing to much of the pathology generating the damage.

“If you put stem cells into an area and you haven’t tried to change the terrain, inflammation will promote stem cells to turn more into scar tissue. That’s not really what we’re looking for, the fibrosis. We make a big deal about this,” Leiber says.

Recommended Supplements

Certain nutrients and supplements can help stem cells grow more efficiently. Regenexx, which specializes in developing stem cell therapies, conducted in vitro studies showing that when stem cells are placed in an environment mimicking an arthritic joint, their growth rate is significantly reduced. They then duplicated the test in various nutrient environments, to determine which nutrients could help the stem cells grow better.

Nutrients and combinations of nutrients that boost stem cell regeneration include vitamins C and D, glucosamine and chondroitin,curcumin, resveratrol, bitter melon, and the amino acid l-carnosine. Leiber recommends these to most of his patients. He also recommends taking a high-quality omega-3 supplement such as krill oil in higher amounts.

“Interestingly, melatonin, which most people are familiar with for sleep … helps stem cells preferentially turn into cartilage over a different kind of cell type. We don’t really know what the right dose is. But it’s safe, it’s cheap, and I think it’s worth taking just because of that information. Other people who I feel may have a need for detoxifying a little bit more, I may add N- acetylcysteine (NAC),” Leiber says.

“If I feel that they have quite a bit of inflammation or I have some testing that tells me they have inflammation, on top of that there’s a product I use that has a mixture of boswellia and willow bark and a whole bunch of different antioxidants, phytonutrients derived from fruits and vegetables. I’ll have them taking them in advance to the procedure as well. If they’re coming with a lot of gut issues, we may start exploring that a little bit and treating that in advance as well.”

On a side note, my latest passion is optimization of mitochondrial function with dietary intervention and supplementation, and many of these supplements are also very useful for improving mitochondrial biogenesis and mitophagy (mitochondrial autophagy). Resveratrol is a particularly intriguing one. It also stimulates SIRT 1, which activates both of those pathways, as does bitter melon and curcumin.

As for diet, you really need to restrict net carbs, which is total carbs minus fiber, to less than 50 grams a day, or maybe even as little as 30 or 40 grams if you’re trying to address chronic dysfunction. Replace those carbs with high-quality fats like butter,coconut oil, cocoa butter, and high-quality fat from pastured animals like tallow or lard.

These are strategies that will help you burn fat for fuel, which burns far cleaner and generates less free radicals, which in turn decreases inflammation. By optimizing your mitochondrial function, you optimize health and life in general. It’s a profoundly effective strategy to not only treat disease but improve longevity.

Anatomy of a Typical Stem Cell Treatment

Leiber specializes in platelet-based procedures and stem cell procedures, which include platelets and growth factors as well. The former are not as involved or expensive as a stem cell procedure. The stem cell protocol generally involves three parts, spread out over three separate treatments. A typical treatment protocol for advanced knee arthritis might go something like this:

1.Prior to your first appointment, or as part of your first appointment, you would get any necessary imaging tests done. Leiber also does a diagnostic ultrasound examination, which allows him to see the tissue structures of the area in question, in real time. The first treatment typically involves prolotherapy to strengthen the ligaments and tendons and create a more hospitable environment for the stem cells.

2.After three to five days, you go back in for a bone marrow aspiration. “I think there’s a lot of unnecessary fear associated with that,” Leiber says.

“I would say 95 percent of the time there’s really only mild discomfort or less associated with it. I numb the skin. I numb down to the bone in the back of the pelvis. Once I know the patient is comfortable, I take a separate tool, and go down to the bone.

There’s no sharp sensation. I let them know I’m about to enter the bone and that they’re going to feel a little bit of pressure … Then I start to draw out some of the bone marrow.”

Very small amounts of bone marrow are drawn at a time, at a slow pace, to prevent achiness. For most conditions, 60 to 100 milliliters of bone marrow will be drawn from four locations on each side of the pelvis. After eating a healthy lunch, you then come back for the injection, consisting of a mixture of stem cells, growth factors, and platelets. Leiber uses image guidance to select the best areas for the injections.

Unfortunately, a local anesthetic at the injection site cannot be used, as it’s been shown to kill the stem cells. But a small amount of local anesthetic in the skin and on the way to the target tissue can be used or a nerve block can be administered (like for a dental procedure), and most patients tolerate these injections very well. You’ll have limited mobility for about three to five days as you have to minimize pressure on the joint. You may also need pain medication during this time.

3.Three to five days later, another blood draw is done, from which platelets and growth factors are separated and extracted and then reinjected into the trouble area. This acts as “fertilizer” for the stem cells that were put in earlier. A brace may be used to protect the area. After that, you’ll need to see a physical therapist for about six weeks.

“In very advanced conditions, in very advanced knee arthritis or hip arthritis, we’ll go ahead and do a concentrated platelet booster at about the six-week mark,” Leiber says.

“When you’re talking about something that’s bone on bone, this is not a cure. For lesser conditions — for tears in ligaments and tendons — this can be a cure; for very advanced arthritis, I think of this more of as a treatment strategy. You may need periodic platelet boosters to maintain the benefits you get from the original stem cell treatment.”

DENGUE FEVER REMEDY.


As dengue is a deadly disease with more than 90% mortality in untreated cases, no established treatment so far till date.

It’s just symptomatic, iv fluids, anti pyretic and platelet transfusion.

As an ardent fan of Ayurveda and also a medical doctor i had seen more than 500 cases of dengue.

This Ayurveda so called cure is just a supplement therapy, not a 100% cure.

Readers are advised to use in with the standard treatment modality.

Pawpaw  (Papaya) Leaf Juice Is A Natural Cure For Dengue Fever

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Remedy:
Two (2) pieces of raw Pawpaw (Papaya) leaves. Clean the leaves and pound and squeeze with a filter cloth. You will only get one tablespoon of juice per leaf. So, take two (2) tablespoons of Pawpaw (Papaya) leaf juice once a day. Do not boil, or cook, or rinse the leaves with hot water, as it will lose its strength. Use only the leafy part of the Pawpaw (Papaya) plant, and not the stem or sap. The juice is very bitter, and you have to swallow it. But it works.
Simple and Effective – blend the leaves, squeeze the juice, drink immediately.
Case Studies:
1. Male student was in a critical condition in the intensive care unit, when his blood platelet count dropped to 15, after a blood transfusion of 15-litres. The boy’s father was so worried that he sought a friend’s recommendation, and his son was saved. He gave his son the raw juice of the Pawpaw (Papaya) leaves. From a platelet count of 45 (after a blood transfusion of 20-litres), and after drinking the raw Pawpaw (Papaya) leaf juice, his platelet count jumped instantly to 135. Even the doctors and nurses were surprised. After two days in hospital, the boy was discharged.
2. Adult female had a very serious case of Dengue Fever, her platelet count had dropped to 28,000 after 3 days in hospital, and water had started to fill up her lungs, causing difficulty with breathing. She was only 32 years old. Her doctor said there was no cure for Dengue Fever, and she’d just have to wait for her body’s immune system to build up resistance against the Dengue Fever, and fight its own battle. She’d already had two blood transfusions, and her platelet count continued to drop since the first day she was admitted to hospital. Fortunately, her mother-in-law heard that Pawpaw (Papaya) Juice would help to reduce the fever. She got some leaves, pounded them, and squeezed the juice out for her. The next day, her platelet count started to increase, and her fever subsided. The Pawpaw (Papaya) Juice was fed to her, and she recovered after three days. Amazing, but true.
3. It’s believed that the body is overheated when suffering from Dengue Fever, and that Pawpaw (Papaya) Juice has a cooling effect. Thus, it helps to reduce the level of heat in the patient’s body, and the fever then goes away.
4. Pawpaw (Papaya) Juice has also been proven to have beneficial effects on sore throats, or when suffering from heat exhaustion (or overheating).

Feel free to write

Email id: oncozene@gmail.com / gladeolie@live.com

Please share your views.

Honest comments and suggestions are always welcome.

 

Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic–Uremic Syndrome.


BACKGROUND

Atypical hemolyticuremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease.

METHODS

We conducted two prospective phase 2 trials in which patients with atypical hemolytic–uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event–free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2).

RESULTS

A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73×109 per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event–free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period.

CONCLUSIONS

Eculizumab inhibited complement-mediated thrombotic microangiopathy and was associated with significant time-dependent improvement in renal function in patients with atypical hemolytic–uremic syndrome.

 

Source: NEJM

Effects of platelet and plasma transfusion on outcome in traumatic brain injury patients with moderate bleeding diatheses.


Coagulopathy and thrombocytopenia are common after traumatic brain injury (TBI), yet transfusion thresholds for mildly to moderately abnormal ranges of international normalized ratio and platelet count remain controversial. This study evaluates associations between fresh frozen plasma (FFP) and platelet transfusions with long-term functional outcome and survival in TBI patients with moderate hemostatic laboratory abnormalities.

Methods

This study is a retrospective review of prospectively collected data of patients with mild to severe TBI. Data include patient demographics, several initial injury severity metrics, daily laboratory values, Glasgow Outcome Score- Extended (GOSE) scores, Functional Status Examination (FSE) scores, and survival to 6 months. Correlations were evaluated between these variables and transfusion of FFP, platelets, packed red blood cells (RBCs), cryoprecipitate, recombinant factor VIIa, and albumin. Ordinal regression was performed to account for potential confounding variables to further define relationships between transfusion status and long-term outcome. By analyzing collected data, mild to moderate coagulopathy was defined as an international normalized ratio 1.4–2.0, moderate thrombocytopenia as platelet count 50 × 109/L to 107 × 109/L, and moderate anemia as 21%–30% hematocrit.

Results

In patients with mild to moderate laboratory hematological abnormalities, univariate analysis shows significant correlations between poor outcome scores and FFP, platelet, or packed RBC transfusion; the volume of FFP or packed RBCs transfused also correlated with poor outcome. Several measures of initial injury and laboratory abnormalities also correlated with poor outcome. Patient age, initial Glasgow Coma Scale score, and highest recorded serum sodium were included in the ordinal regression model using backward variable selection. In the moderate coagulopathy subgroup, patients transfused with FFP were more likely to have a lower GOSE score relative to those who did not receive a transfusion (OR 5.20 [95% CI 1.72–15.73]). Patients with moderate coagulopathy who received FFP and packed RBCs were even more likely to be have a lower GOSE score (OR 7.17 [95% CI 2.12–24.12]). Moderately anemic patients who received packed RBCs alone were more likely to have a worse long-term functional outcome as determined by GOSE and FSE scores (GOSE: OR 2.41 [95% CI 1.51–3.85]; and FSE: OR 3.27 [95% CI 2.00–5.35]). No transfusion types or combinations were noted to significantly correlate with the 6-month mortality in ordinal regression.

Conclusions

In TBI patients with moderate coagulopathy, FFP transfusions alone or a combination of FFP and packed RBCs were associated with poorer long-term functional outcomes as measured by the GOSE. Red blood cell transfusions were associated with poor long-term functional outcome in TBI patients with moderate anemia. Platelet transfusion in patients with moderate thrombocytopenia was not significantly associated with outcome. Although transfusion is beneficial to many patients with severe hematological abnormalities, it is not without risk, and the indications for transfusion should be carefully considered in patients with moderate hematological abnormalities.

Source: Journal of neurosurgery

 

 

 

Coating on Aspirin Might Reduce Its Cardioprotective Effects.


Enteric coating can affect aspirin‘s inhibition of platelet aggregation, according to a study in Circulation.

Researchers used three assays — platelet aggregation, serum thromboxane formation, and urinary excretion of a thromboxane metabolite — to test response to an oral dose of 325-mg immediate-release or enteric-coated aspirin in 400 healthy volunteers (median age, 26). The study was partly funded by Bayer HealthCare.

No participant showed resistance to the immediate-release formulation. Up to 49% showed resistance to enteric-coated aspirin, but most were not resistant upon retesting.

The authors conclude that “we failed to find a single case of true drug resistance” and that their findings show “inconsistent platelet inhibition” after ingestion of enteric-coated aspirin.

Source: Circulation

 

Therapeutic vs. Prophylactic Platelet Transfusions


Prophylactic platelet transfusions might not be needed for thrombocytopenic patients undergoing stem-cell transplantation, but are indicated for those receiving chemotherapy for acute myeloid leukemia.

Current practice is to give platelet transfusions to patients with hematologic malignancies when platelet counts decline to 10,000/µL. However, fewer platelet transfusions might be required if they were limited to thrombocytopenic patients with clinically important bleeding (WHO grade 2), regardless of the platelet count.

To determine the feasibility and safety of this approach, German investigators conducted a prospective, open-label, multicenter study involving 391 patients receiving chemotherapy for acute myeloid leukemia (AML) or undergoing stem-cell transplantation (SCT) for hematological cancers. Patients were randomized to receive platelet infusions when their morning platelet counts were 10,000/µL (prophylactic group) or only when they experienced grade 2 or higher bleeding (therapeutic group). Patients were assessed twice daily and all new bleeding, headaches, or other cerebral symptoms were investigated. Results were as follows:

  • The therapeutic group required fewer transfusions than the prophylactic group (mean, 1.63 vs. 2.44; P<0.0001), but experienced a higher rate of bleeding (42% vs. 19%; P<0.0001), including more grade 4 bleeding (5% vs. 1%; P=0.02).
  • AML patients experienced more bleeding than SCT patients (37% vs. 18%; P<0.0001); only AML patients experienced grade 4 bleeding, including two episodes of fatal cerebral hemorrhages in the therapeutic group.
  • The therapeutic and prophylactic groups experienced similar overall survival, number of red blood cell transfusions, duration of thrombocytopenia, and number of days in the hospital.

Comment: The indications for platelet transfusions require continued review, and pegging their use to a specific platelet count might not always be appropriate (JW Oncol Hematol Feb 17 2010). As this study shows, thrombocytopenic SCT patients infrequently experienced major hemorrhages, so therapeutic platelet transfusion might be more appropriate for this population. In contrast, predicting bleeding does not seem possible in thrombocytopenic AML patients, even with careful monitoring. So platelet transfusions only for bleeding might be more appropriate for these patients.

Source: Journal Watch Oncology and Hematology