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Magnetic MAGEC Spine Lengthening Metal Rod Device For Noninvasive Scoliosis Treatment

Magnetic MAGEC Spine Lengthening Metal Rod Device For Noninvasive Scoliosis Treatment

MAGEC Spine LengtheningIt seems that the technology for bone lengthening is finally starting to expand further. Where before it was just the long bones like the femur, tibia, and humerus, the same type of technically is being applied to the irregular bones of the torso aka the vertebrate bones. We became aware of this unique form of bone lengthening after finding at least two sources where this new type of bone growth was talked about.

It may seem like a stretch for the 2nd source to say that a boy grew 6 full inches from using magnets to stretch out his curved spine but the pictures seems to show that he did indeed get just that. We remember reading about a similar story about another boy last year who got a similar type of treatment. Magnet implants were placed into his leg bones to stretch out the bones from using E&M fields which were applied noninvasively.

Now, there is this technology. It turns out that the MAGEC Spine Lengthening device is a type of magnetic rod inserted into the spine and then slowly lengthened from passing some level of magnetic force to the rods, stretching the rods out.

The First Story – It was published just a few days ago in August of 2014. An orthopedic surgeon named Dr. Michael Vitale says the technology is ‘a game-changer. The 6 year old boy getting the surgery is a Jeremiah Knowlton from Allendale, NJ. Quoted from the article…

To correct his scoliosis, Jeremiah first had surgery in April to implant an adjustable rod in his spine. In that surgery alone, Vitale was able to reduce his spine curvature from 72 degrees to about 20 degrees — a 50-degree correction, when only 30 degrees were expected….At last week’s first lengthening procedure Vitale took the hand-held MAGEC device and glided it over Jeremiah’s back so it synced with the rod and could pull it 5 millimeters. It took just a few minutes. Jeremiah will have the noninvasive procedure — which is done to keep up with normal spine growth and maintain the curve correction — every three months until he’s a teen”

It seems that it wasn’t until Feb of this year that the MAGEC device was approved by the FDA, but had already been used in 24 countries and helped so far around 750 children with scoliosis problems.

The Second Story – This was published around April of this year (2014) about this boy named Thaine Marston. His parents found out about the therapy called the Magnetic Expansion Control treatment. Over a span of 18 months, the device increased his height by 6 full inches. As explained by the article…

“MAGEC works by inserting an adjustable magnetic growing rod into the patient’s spine which can then be controlled by an external remote control….The rod is then lengthened by magnets outside the body which communicate with the magnets under his skin gradually straightening the spine

The original doctor was a Consultant paediatric spinal surgeon Masood Shafafy.

The entire operation took a full 5 hours, but the hospital stay was around 6 days. After that, the patient/Thaine was back on his feet. He would eventually go from 4′ 9″ to 5′ 3″. As Thaine continues to grow, surgeons can continue to straighten his spine. All they have to do is put an external magnet to his back and slowly stretch out the magnet. However, to lengthen the magnets, you have to go back to the hospital every 6 weeks. 

What does the MAGEC treatment imply to us as normal people who want to be taller?

Not much, but it is a great indication just how fast biomedical technology and innovation is going these days. Not only that, when I looked at the website which is designing and selling the MAGEC Device, I found out that they are the same company that is selling the PRECICE Limb Lengthening Device, called ELLIPSE Technology. If you guys remember, the PRECICE Internal aka Intramedullary Nail was the device that was patented and designed by Dror Paley and only had been FDA Approved maybe 2 years ago, when the website was first started. Refer to either the MMT Forums or the Limb Lengthening Forums for much more information about the PRECICE Device.

When I look at the MAGEC and the PRECICE, it seems that both of the devices work on a very simple concept on how the technology works (which is what both the MAGEC and the PRECICE really are). The metal rod is made from a metal alloy that is not allergic when placed in the human body, it won’t be attacked by the patient’s own immune system, it is non-biodegradable. It is also lightweight but very strong, withstanding lateral forces which might bend it and/or break it.

I am NOT sure whether the PRECICE limb lengthening metal rods works on the magnetic force concept but the MAGEC metal rod stretched out by the magnets inside. Like the one’s developed by Dror Paley, you will of course still need at least two surgeries, one to pu tin the rods and securely fasten the rods into place on the bone so that the rods don’t shift and move around. The 2nd surgery is to remove the rods once the bones grow during normal natural to the adult size.

What makes the MAGEX is revolutionary is where the surgeons don’t have to go into the developing boy with scoliosis’s back every 6 month for more invasive surgery to correct for the spine curvature as the boy is still growing taller and their spines grow more curved. The non-invasive approach saves on time, money, and effort to make the growth of the spines more natural.

Achondroplasia Treatment and Increase Height Using Meclozine aka Meclizine – Great News For Parents!

Achondroplasia Treatment and Increase Height Using Meclozine aka Meclizine – Great News For Parents!

MeclozineWe have already talked about the chemical BMN-111 by Biomarin which is supposed to be able to treat young children with open growth plate cartilage suffering from Achondroplasia. Achondroplasia is the most common type of skeletal disorder which causes people to end up with abnormally short stature, often below the dwarf/small people height of 4′ 10″.

Now there seems to be another chemical treatment that has been proven to have benefits to help treat achondroplasia by inhibiting the FGFR3 gene abnormality. This compound is called Meclozine or Meclizine.

Refer to the study…

Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

From the abstract…

….We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias

We’ve seen already at least 1 Patent (by Nakao) filed which was used to treat idiopathic short stature using a type of C-natruretic peptide (CNP). This compound seems to work just as well for skeletal dysplasia as any of the CNP derivative types.

For more information on Meclozine/Meclizine, refer to its Wikipedia article here.

From the article, all these brand name pills have as the active ingredient meclizine inside…

  • Bonine
  • Bonamine
  • Antivert
  • Postafen
  • Sea Legs
  • Dramamine (Less Drowsy Formulation)
  • Emesafene

On its Wikipedia page, it says that this compound is supposed to be used for motion sickness, but has dementia enhancing effects on older people.

The conclusion made by that researchers are the following…

We found that meclozine dihydrochloride, a commonly used anti-emetic drug for its anti-histamine activity, efficiently suppresses FGFR3 signaling in three different chondrocytic cell lines and embryonic bone organ culture. We also identified that meclozine suppresses FGF2-mediated phosphorylation of ERK”

Clinical dosage of meclozine promotes longitudinal bone growth, bone volume, and trabecular bone quality in transgenic mice with achondroplasia.

“Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3). No effective FGFR3-targeted therapies for ACH are currently available. By drug repositioning strategies, we identified that meclozine, which has been used as an anti-motion-sickness, suppressed FGFR3 signaling in chondrocytes and rescued short-limbed phenotype in ACH mouse model. Here, we conducted various pharmacological tests for future clinical application in ACH. Pharmacokinetic analyses demonstrated that peak drug concentration (Cmax) and area under the concentration-time curve (AUC) of 2 mg/kg of meclozine to mice was lower than that of 25 mg/body to human, which is a clinical usage for anti-motion-sickness. Pharmacokinetic simulation studies showed that repeated dose of 2 mg/kg of meclozine showed no accumulation effects. Short stature phenotype in the transgenic mice was significantly rescued by twice-daily oral administration of 2 mg/kg/day of meclozine. In addition to stimulation of longitudinal bone growth, bone volume and metaphyseal trabecular bone quality were improved by meclozine treatment. We confirmed a preclinical proof of concept for applying meclozine for the treatment of short stature in ACH, although toxicity and adverse events associated with long-term administration of this drug should be examined.”

“Twice-daily oral administration of 1 and 2 mg/kg/day of meclozine reverses the dwarfed phenotype in Fgfr3 ach mice. (A) A representative image of the individual female littermates at the end of treatment demonstrated that an untreated Fgfr3 ach mouse reveled the dwarfed phenotype, which was rescued by oral administration of 2 mg/kg/day of meclozine treatment. (B) Relative body length of the wild-type mice and Fgfr3 ach mice was calculated based on the body length of untreated Fgfr3 ach mice at 0 day. The body length of 1 or 2 mg/kg/day of meclozine-treated Fgfr3 ach mice was larger than that of untreated Fgfr3 ach mice throughout the treatment period. On the other hand, 20 mg/kg/day of meclozine-treated Fgfr3 ach mice were not larger than untreated Fgfr3 ach mice at the end of treatment. Mean and SD are indicated. Statistical significance was analyzed by the unpaired t test for each dose of meclozine-treated Fgfr3 ach mice (n = 7, 5, and 4 for 1, 2, and 20 mg/kg/day of meclozine, respectively) or untreated wild-type mice (n = 16) versus untreated Fgfr3 ach mice (n = 15).”

Interesting that the higher dose did not help to increase length.  This could be why it’s so hard for meclizine to be effective in humans.  There’s an equilibrium dosage that’s hard to pinpoint.

Warning: We are not doctors or medical professionals. We would like to tell any parents of kids suffering from Achondroplasia/Short Stature to NOT just go down to the local drugstore and buying bucket-loads of Dramamine, the Less Drowsy Formulation, to try to treat/inhibit/suppress the FGFR3 abnormality. Please seek professional advice first before going off and try to make your children taller.

Does DHEA Dehydroepiandrosterone Help People Grow Taller and Increase Height?

Does DHEA Dehydroepiandrosterone Help People Grow Taller and Increase Height?

One of the regular readers of the site asked us whether the compound known as Dehydroepiandrosterone would have the benefit of increasing a person’s height. I personally have never done much research on this compound, but I do know about its intended effects based on the Body Building forums and other people talking about it for muscle mass gains.

Years, ago Tyler had said that the compound would in fact have a negative effects on growth. The post was “New Growth Spurt by inhibiting DHEA?”. The study referenced would be “DHEA suppresses longitudinal bone growth by acting directly at growth plate through estrogen receptors“. In that post, he argued that there was a 2nd study that showed that by using a type of compound known as ACE Inhibitor, it would lower the level of DHEA in older men. Certain cheese types with this bacteria known as Lactobacillus helveticus is supposed to be a good easy way to obtain a form of ACE Inhibitor.

That is Tyler’s arguement on the effects of DHEA. However, there are a few claims on the internet which claim that DHEA is supposed to help with height increase. The main source to these claims was some guy named Ray Peat. His claim on getting 1.5 Inches of height from using it, as well as many other benefits was something that many people talked about. It would be referenced even in the LSJL Forums. Refer to the thread “46 year old man grows 1.5 inches taller while testing DHEA.“. I don’t know anything about this Ray Peat guy or anything he wrote but most people say that Peat would not try to lie or scam people. He has some crazy claims but he is being genuinely honest about those assessments.

Supposedly…

  • His wisdom teeth which was being impacted rotated
  • He gained 1.5 inches in height
  • His waist shrunk
  • One of his moles dropped off
  • Gray hair reversed to younger hair color

The PubMed studies that are referenced have said this about DHEA…

  • It has similar effects like HGH, where it can sort of make the body act younger
  • There is a sort of reversal of age phenomena with this compound
  • It is supposed to have beneficial effects on depression and cognitive function
  • It increased the level of sexual energy in men who have low libidos
  • It seems to have inflammatory inhibitory effects, and has some benefit towards the symptoms of arthritis.

My Personal Educated Guess

This compound that both Tyler and others talk about, seem to be on the surface have contradicting information. Tyler says it inhibits growth, while other people say it promots growth. How can such a compound exist?

It actually makes a lot of sense, when you remember that HGH therapy makes young kids reach bone maturity faster. This compound known as DHEA is just like HGH.

So why & how did this Ray Peat guy end up taller at the age of 46 from taking DHEA?

DHEA seems to lead to bone growth, but only in the form of bone mineral density (BMD) increasing. This is similar to HGH. If an older person took HGH, they would notice a BMD increase as well.

Most people who are in their 40s are already starting to loss height from poor posture and low BMD. It is actually shown that low BMD levels in bones will not just cause osteoporosis but also height loss in later in life. Japanese women is especially prone to this. When I visited Japan a few years ago, I lost count on the number of older Japanese women I saw who had completely hunched backs or curved spines, due to a diet of low Calcium and VItamin D. If you took compounds that could reverse that bone mineral density loss, the lost height can be gotten back.

Remember: I like the readers to remember the one story about the women who took Vitamin K2 at mid-age (58 years old) and ended up 4 cms taller too. (Refer to “Increase Height And Grow Taller Using Vitamin K2 aka Menaquinone (Important!)”)

What most likely happened to Ray Peat is that he got back some of the height he lost due to getting older.

Questions Answered

So does DHEA have benefits for looking and feeling younger? – There seems to be enough PubMed studies which validate this idea. You get a boost in sexual desire, energy, youthful look, etc.

Does taking DHEA make a person taller? – Similar to HGH, it might if the person has already suffered height loss from BMD decreases due to older age, and poor posture. If you are a teenager, or early 20s, it probably won’t work on you.

Does DHEA help with depression and cognitive functions? – There is so far some evidence for this. Do a search on PubMed about the effects.

Does DHEA have a bad or good effect on the growth plates? – It seems to make young bones reach bone maturity faster. In the long run, it has a negative effect. It increases the level of testosterone in the body system, so if you are young enough, you will actually reach puberty faster and ultimately end up shorter in adult height.

Like progesterone and other estrogen stimulating/increasing chemicals out there, DHEA seems to increase the level of estrogen in the body. Increases in estrogen is correlated to increases in BMD. That is why you find that for women who go into menopause, where estrogen production is dropped almost completely and grandmothers start to get facial hair like moustaches, the onset of osteoporosis goes up dramatically.

Conclusion

DHEA is not good for the body for height increase in the long term. There is a small minority of people where DHEA would make them taller, by increasing bone mineral density which would fix their osteoporosis likelihood and maybe improve their posture and spinal curvature. It has similar effects as HGH, where the older person taking it will have some age-reversal effects to them.

Only if you are in your 40-60s, have low BMD, and suffer from some level of spinal curvature will the DHEA have height increasing effects.

Specific Bones Do Grow Bigger After Skeletal Maturity And Growth Plate Closure

Specific Bones Do Grow Bigger After Skeletal Maturity And Growth Plate Closure

I believe that even in our normal day to day life most people would be able to observe from being around a person who is going through the puberty phases in life changes to their body occurring which suggest bones are growing bigger as well.

Of course, we are not just talking about the interstitial growth of bones here. What were are saying is that there are certain bones in the human body which keep on growing in size even after all the growth plates are closed.

The evidence is from certain studies, like…

Surprising evidence of pelvic growth (widening) after skeletal maturity

It seems that while the long bones may no longer be growing vertically, they do indeed grow in width.

Of course, we already know that the long bones grows appositionally thicker over the years as the inner cambium periosteum layer deposits more and more osteoblasts onto the bones, but this is different. What we are see is an irregular bone structure, the pelvic bone becoming wider.

This makes sense due to two main things…

Factor #1: Many females have said that after going through with pregnancy and having their babies the natural way, they noticed that their hips expanded in size, and have never gotten back down to the size before they were ever pregnant. The phenomena tells us that somehow during pregnancy the pelvic bones were expanded in width.

Growth Plate ClosureFactor #2: The most common phenomena where the shoulders of a young teenage boy after they finish growing taller seems to grow in width and the overall torso seems to also grow wider, aka “filling out”

It would turn out after looking at the locations of cartilage in the body, the sternum/rib cage area of the body even in young teenage boys who have no more cartilage to grow taller, there is still cartilage in their front ribcage area. That is what makes the males grow wider in the shoulder area around the ages of 17-25.

Remember: When archeaologists are digging up cities from thousands back, they find skeletons with the entire ribcage being bones, which suggests that sometime after the bones that make height are bones, the ribcage which is made from fibrocartilage also slowly ossifies over time. If humans had cartilage in the front that never ossified, then the dug up skeleton from thousands of years ago would be missing the front area/sternum which is supposed to be surrounded by Costal Cartilage. Cartilage does not survive buried under ground for thousands of years. It either ossifies or gets disintegrated.

So what we are seeing is two different areas of the body that are still growing!

  1. The rib cage
  2. The pelvic region

In my long post about the possible reason for why some pregnant women grew taller, I had pointed at the related phenomena of pelvic girdle pain, where the little bit of cartilage (at the Symphysis Pubis) becomes stretched out, making the entire pelvic bone wider. After the findings on the ligament stretching and relaxing effects of relaxin, which is also released during pregnancy, it started to made sense. For example, the pelvic structure of females and males are already different. On average, the hips of a woman’s is proportionally larger than a mans, for childbirth and for easier passage of the baby through the birth canal.

During pregnancy, the entire area becomes widened from relaxin & the drop in calcium levels in the lumbar bones in the mother as the calcium gets transported to the developing embryo in the uterus, which means the bones become widened aka bigger. The loss in Ca means that the bones do get much weaker which means that it might be easier to stretch out the bones and remodel them.

There is now medical confirmation that certain bones in the body do keep getting bigger volumetrically. Refer to the following below…

From the 2nd source, it is written the following….

By the age of 18 years the girls had reached their mothers’ height (101%) and humerus, radius, femur and tibia lengths (100-101%), but not their mothers’ shoulder, great pelvis and lesser pelvis widths (98%, 95% and 93%, respectively). Our data confirmed that, after bone elongation had ceased, segment width continued to increase, although at a slower speed, into early adulthood.

If the pelvic bones are getting bigger, aka wider, how can we then use that type of knowledge to make the overall skeleton longer then?

Amateur Chinese Researchers Are Extremely Educated On Bone Interstitial Growth – Important!

Amateur Chinese Researchers Are Extremely Educated On Bone Interstitial Growth – Important!

Something that I have speculated on for a long time is that there are dozens, if not hundreds of individual amateur level researchers around the world like us, and I had said that most of them who are highly educated and understand the mechanics of the bone as well as any MD trained orthopedic specialist would be probably from Russia, Sweden, The Netherlands, Germany, South Korea, Japan, or China. Those are the only few countries which have the level of education, and technology sophistication to be able to play with the more advanced subjects.

I track the sources which link to this website. A link to the website has made my speculations much more concrete. It is from a Chinese based website source, and the level of knowledge expressed is above what I even understood, until I started to digg further into the technical details. Refer to the link http://bbs.wenxuecity.com/health/468959.html

The text on the page is completely in a language which I don’t understand, but fortunately for Google Chrome, it was roughly translated. I posted the translated parts below.

Chinese Researchers Extremely Educated

Bone Interstitial GrowthSome background notes on this website called Wen Xue City – After looking at its Wikipedia page, it seems that it is not some local city forum, but a very well known website that is used by the Chinese Expat community. It is supposed to be the…”largest overseas Chinese website”. From the Wiki pages, it is supposed to get around 2 Billion page views every month, and with 3 million unique visitors (is it by per day??).

First, whoever gave the reply to this person who wanted to grow taller and lengthen their bones understood the details on how Wolff’s Law is supposed to work when you put loads in certain directions on a bone. They are using words to describe which direction to apply pressure on and what would happen to the bone.

The mention of the Mechanostat Theory by Harold Frost was something I only glanced at early on in the website and forgot about. What happened is that after Wolff came out with his law, Frost came along and adjusted that law aka refined it to be much more specific and detailed on what exactly happens to the bone, while still accepting the original law laid out by Wolff.

When the poster is talking about this term called “radial” I believe that they are talking about a lateral/side force/pressure used. This is similar to what Tyler proposes aka applying force laterally.

I also agree with him that if you are going to be applying a static force, the bones will not be remodeled. You need a dynamic, intermittent type of loading.

They also understand that the increase in bone thickness will always be in the area of bone which is concave in nature.

Here is the amazing point which is made, which I did not reach yet. Remodeling of bone is not possible unless the bone is curved aka concave in the area which you want to thicken/add bone to. It is not the force/pressure/load that is causing the bone to remodel, but the curved/concave nature of the surface of the bone.

Whoever wrote the post seemed to be writing it maybe for the purpose of figuring out how to grow bone density to reverse osteoporosis in the elderly, but they might also be talking about bone volumetric growth, aka making the bones bigger/longer.

What makes this link so important, and what are the implications?

If these guys were talking about how to make the bones longer for height increase, then they are much further ahead in understand the mechanics of the bone than me at least. If they are instead trying to learn Frost/s refined rule on Wolff’s Law for just increased bone density for preventing or treating osteoporosis, then they are still extremely advanced.

I think that there are probably websites and forums in the Russian, Chinese, and German internet space which are looking at the same PubMed studies like we are and have a much better grasp and understanding on what are the technical problems, and issues that are most important which we must resolve to push the effort forward.

If the person who wrote that reply (with all those pictures and diagrams on the effects of loading a femur) is any type of indication of the scientific level of bone mechanics expertise, I would then say that even these amateur level Chinese height increase researchers are much further than where we are. So did they figure out something already? I don’t think so, unless the government or military have done it and decided not to publish their top secret research and findings.

I have always believed that there are certain government groups anonymously tracking and following this website. We are not the normal type of blog talking about cooking recipes and putting Facebook pictures of their kids up. These days with the ability to get Private VPN services, and use local proxies to hide one’s IP, it is almost certain that I can not even figure out who are these people who are secretly reading the website and taking the information I leak to use for their own benefit.

I have already proved that the professional researchers in the Chinese Military Hospitals have been working to get the surgery of growth plate transplantation to work out for at least 2 decades now and that teams in a few Russian Cosmetic Clinics are also trying to get the exact same type of surgical technique to work out as well, by growing the growth plates from surgically removed fat tissue.

Pressure plasma for height

Non-Thermal plasma is plasma that is not in thermodynamic equilibrium.  Atmospheric pressure plasma matches the pressure of the surrounding atmosphere.

Non-Thermal Atmospheric Pressure Plasma Enhances Mouse Limb Bud Survival, Growth and Elongation.

“appendage regeneration is dependent on reactive oxygen species (ROS) production and signaling. Mesenchymal cell stimulation by non-thermal (NT)-plasma, which produces and induces ROS, would (1) promote skeletal cell differentiation and (2) limb autopod development. Stimulation with a single treatment of NT-plasma enhanced survival, growth and elongation of mouse limb autopods in an in vitro organ culture system. Noticeable changes included enhanced development of digit length and definition of digit separation. These changes were coordinate with enhanced Wnt signaling in the distal apical epidermal ridge (AER) and presumptive joint regions. Autopod development continued to advance up to 144 hr in culture, seemingly overcoming the negative culture environment normally observed in this in vitro system. Real time qPCR analysis confirmed the up-regulation of chondrogenic transcripts. Mechanistically, NT-plasma increased the number of ROS positive cells in the dorsal epithelium, mesenchyme and the distal tip of each phalange behind the AER, determined using dihydrorhodamine. The importance of ROS production/signaling during development was further demonstrated by the stunting of digital outgrowth when anti-oxidants were applied. NT-plasma initiated and amplified ROS intracellular signaling to enhance development of the autopod. Parallels between development and regeneration, suggest the potential use of NT-plasma could extend to both tissue engineering and clinical applications to enhance fracture healing, trauma repair and bone fusion.”

“Vertebrate limbs grow through the coordinated activity of numerous growth factor signaling pathways, including the Wnt, fibroblast growth factor (FGF), bone morphogenetic protein (BMP), Notch, and transforming growth factor-β pathways. ROS play a primary role in mediating the activity of these factors and/or are integrally involved in regulating downstream signaling pathways. For example, a sustained increase in ROS levels is required for Wnt β-catenin signaling and the activation of one of its main downstream targets, fgf20. In addition, naturally occurring oxidative spikes are observed in most of the transition stages throughout developmental and regenerative processes. Furthermore, there is precedence for ROS production to both direct and enhance mesenchymal cell differentiation into either chondrocyte or osteoblast lineages”

“Since the NT-plasma discharge occurs in air, it is a highly complex mix of reactive chemical species (i.e., nitric oxide [NO], ROS, oxygen singles, and ozone), free ions, visible, ultraviolet, and near-infrared light, electric fields, and electromagnetic (EM) radiation.”

“one study showed that a 2 h treatment with EM field stimulated limb growth through increased proliferation and chondrocyte differentiation”

That is an absolutely huge elongation.

“Morphological formation of the joint region and alcian blue staining of proteoglycan appeared normal in sham and NT-plasma-treated digits. Chondrocytes in the proximal segment of the sham-treated digit were entering the prehypertrophic stage, based on the larger size, greater cellular spacing, and decrease in proteoglycan (white arrowhead). This typically precedes the formation of the primary center of ossification in the diaphysis. In contrast, chondrocytes from the NT-plasma-treated digit were immature and contained large amounts of proteoglycan. Even more striking was the much larger cartilage phalangeal segments in the NT-plasma-treated digit. A white line with double arrows marks the joint between the first and second phalanges in both sections. In the sham-treated digit, the adjacent joint spaces (white arrow) can be clearly observed; whereas in the NT-plasma-treated digits, there is no evidence of the next joint space, due to the increased segment length.”<-So maybe the plasma treatment increases stem cell differentiation to chondrocytes which is what we’d be looking for.

“Histology and quantitative real time-polymerase chain reaction were used to assess chondrogenesis and molecular events associated with the accelerated development. (A) A representative, hematoxylin and eosin (H&E) and alcian blue stained sections of middle phalanges from sham and NT-plasma-treated limb autopods. A white double arrow line marks the first joint space. The white arrows mark adjacent joint spaces, and the white arrowhead marks prehypertrophic chondrocytes in the sham control. (B) At 24 h post-NT-plasma treatment, alkaline phosphate (ALKP), catalase (CAT), endothelial nitric oxide synthase (eNOS), and bone morphogenetic protein 2 (BMP2) expression increased twofold above control. BMP4 and runt-related transcription factor 2 (Runx2) increased 12-fold and 8-fold, respectively, and fibroblast growth factor (FGF)-2 showed no increase. One hundred forty-four hours later, increases for ALKP (6-fold), CAT (14-fold), and BMP2 (3.5-fold). eNOS remained increased twofold above control at 144 h. BMP4 and Runx2 showed a relatively consistent elevated expression at 24 and 144 h. The results are expressed as the mean±standard deviation (n=3 [two limbs pooled per sample], *p<0.05). ”

“NT-plasma treatment promoted both growth and differentiation of cartilaginous elements within the embryonic mouse autopod. Based on the lack of limb growth after NT-plasma treatment in an antioxidant environment, and the increase in H2O2-positive cells in and under the epithelia throughout the 6 day culture period, we propose that NT-plasma induction of intracellular ROS also plays a role in the growth and differentiation observed in the autopod. In addition, H2O2-positive cells were observed in the distal digit tips behind the AER, concurrent with enhanced Wnt signaling. These findings are consistent with the ROS dependence of signaling factors (e.g., Wnt, BMP, and FGF) required for autopod development.”

“ROS production may not be the sole mechanism driving enhanced autopod growth. A second possible reason that NT-plasma enhanced autopod growth was its inhibition of epithelial overgrowth. ”

“In limb regeneration, a thickening of the epidermis has been shown to inhibit signaling to the blastema, halting the regeneration process.”

Hard to determine causality as there are so many potential causal factors as there are so many confounding variables in plasma.