I think this PubMed study is one of the biggest breakthroughs I have ever found on the possibility of reforming the Epiphyseal Plates. 

The articles is entitled “Thyroxine Is The Serum Factor That Regulates Morphogenesis Of Columnar Cartilage From Isolated Chondrocytes In Chemically Defined Medium” – Author: R. Tracy Ballock, & A. H. Reddit (source link) There is a full article PDF to the link above.

The first thing that I notice right away is that the primary author is Robert Ballock, who Tyler introduced me to the work in the very beginning when he directed me to the work of Zhang for the Loading Modalities and Ballock for his studies on regrowing and regenerating new growth plates.

Analysis: While I haven’t read the entire paper yet, the abstract reveals for the first time conclusive evidence that with a slight manipulation of the serum concentration in the medium, in terms of adding thyroxine, the chondrocytes developed into the stacking column architecture that is only seen in growth plates, and not any other type of hyaline, fibrocartilage, or articular cartilage. The 3-D aggregates all seem to have the columns in a certain directions which means that these chondrocyte pellets are basically small pieces of completely regenerated growth plates. Remember that the main difference between the growth plate cartilage and the other type of cartilages, even the other hyaline cartilage was the way the chondrocytes were able to align themselves on top of each other in columns.

Not only that, we see that the chondrocytes also are expressing the right type of Collagen, Type X, as well as the right level of alkaline phosphatates, which is the type you see in completely differentiated chondrocytes which means they are going through hypertrophy. The key growth regulator they found was that it was thyroxine.potentially, I would say now that you can take these newly formed “cartilage” pellets and implant them into human long bones in a thick enough defect section and the bones can theoretically lengthen due to the hypertrophic effects.

Abstract

Epiphyseal chondrocytes cultured in a medium containing 10% serum may be maintained as three dimensional aggregates and differentiate terminally into hypertrophic cells. There is an attendant expression of genes encoding type X collagen and high levels of alkaline phosphatase activity. Manipulation of the serum concentration to optimal levels of 0.1 or 0.01% in this chondrocyte pellet culture system results in formation of features of developing cartilage architecture which have been observed exclusively in growth cartilage in vivo. Cells are arranged in columns radiating out from the center of the tissue, and can be divided into distinct zones corresponding to the recognized stages of chondrocyte differentiation. Elimination of the optimal serum concentration in a chemically defined medium containing insulin eliminates the events of terminal differentiation of defined cartilage architecture. Chondrocytes continue to enlarge into hypertrophic cells and synthesize type X collagen mRNA and protein, but in the absence of the optimal serum concentration, alkaline phosphatase activity does not increase and the cells retain a random orientation. Addition of thyroxine to the chemically defined medium containing insulin and growth hormone results in dose-dependent increases in both type X collagen synthesis and alkaline phosphatase activity, and reproduces the optimal serum-induced morphogenesis of chondrocytes into a columnar pattern. These experiments demonstrate the critical role of thyroxine in cartilage morphogenesis.

I was watching this youtube video (source link) and something the MD talked about I think is really important was the mention on how at least certain growth plates close. There seems to be a direction on how the growth plates close.

He was talking about a very specific type of growth plate injury that happens a lot to young kids who get injured playing sports. It is a special type of the Type III Salter Harris Fractures known as the Tillaux Fracture. The thing is that this type of fracture doesn’t really happen in adults only kids. What I learned is from the section 7:15-8:15 section of the video so if you want to skip to that part, that’s fine too. The thing is this…

Ankle growth plates don’t close uniformly but close from a medial to lateral direction.

We know that the fibula distal end is connected to the tibia with a ligament. This means that the medial side of the growth plate closes before the lateral side. Any type of torsional load (twisting) can cause the medial section which is attached to the fibula end can snap/ break off because of the fact that one side of the growth plate is ossified and has become bone while the other side might still have some cartilage left.

I thought I could help out the regular and future readers (as well as myself) in understanding the possible ways the mesenchymal stem cells can differentiate into with a picture I found from a PubMed study. The study and article is entitled “Adult mesenchymal stem cells and cell-based tissue engineering.” (source link).

Note: For the complete article file in PDF form, click HERE.

Arthritis Res Ther. 2003;5(1):32-45. Epub 2002 Dec 11.

Adult mesenchymal stem cells and cell-based tissue engineering.

From the bottom of the source link page….

Lineage potential of adult human MSCs. MSCs are characterized by their multilineage differentiation potentials, including bone, cartilage, adipose tissue, muscle, tendon, and stroma. This figure depicts some of the in vitro culture conditions (boxed) that promote the respective differentation process into a specific lineage. Signaling pathways and/or components or events shown to be involved in lineage-specific differentiation are in italics. See text for details.

Dotted arrowheads denote potential ‘reverse’ differentiation events. bFGF, basic fibroblast growth factor; bHLH, basic helix–loop–helix; BMP, bone morphogenetic protein; Cbfa1, core binding factor alpha 1; ECM, extracellular matrix; FGF, fibroblast growth factor; GDF, growth/differentiation factor; IBMX, 3-isobutyl-1-methylxanthine; LRP, low-density lipoprotein receptor-related peptide; MAPK, mitogen-activated protein kinase; PDGF, platelet-derived growth factor; SMAD, vertebrate homologue of DrosophilaMothers Against Decapentaplegic (MAD); TGF-β, transforming growth factor beta; WISP, Wnt-1-inducible protein.

Analysis:

We can see that the mesenchymal stem cells are a type of multi-potent progenitor stem cell which seems to be able to differentiate into many different types of cell types. In the article we learn that the mesenchymal stem cell is one of the main ideas people have for using the stem cells in tissue engineering.

If we focus just on the bones and cartilage, we can see that the picture is very clear in listing 1. the pathway, and 2. the types of growth factors or modulating factors which will help lead the mesenchymal stem cell to its desired outcome.

1. Bone

• Pathway and cause: LRP-5/Wnt Signaling, Telomerase & Cbfa-1
• Needed growth factors: Dexamethasone, BMPs, Ascorbate, Beta-Glycerophosphate, 1-25- DihydroVitamin D3,

2. Cartilage

• Pathway and cause: Cell Adhesion, SMADs, WISP-3/Wnt Signaling, MAPK, ECM Interactions, and Sox9
• Needed growth factors: High-density pellet culture, Serum-free media, Dexamethason, Ascorbate, TGF-Betas (1 & 2), BMPs

A random thought I recently had was that the way so many different types of tribes and groups of ethnicities had come and gone and the many variations, combinations, and permutations of human body types should result with an extremely high probability that at some point in the history and evolution of the hominid species from the great apes to humans, there had to have been at least 1 tribe or group of human like creatures who grew to at least 8 feet tall.

My thinking process is that if we reverse the time scale back to our primitive ancestors, their lives were far more simple than ours. They didn’t have to worry about jobs, insurance, businesses, investing, school, etc. which we have to deal with in our modern life. What they had to worry about was what most social creatures had to worry about.

Food, water, access to mating partners, having healthy offspring, staying away from danger, staying alert, etc. These are the things they worried about. At this basic level, most hominid which started to walk upright probably developed the realization that being taller was better than being shorter. There is a clear advantage in reaching food in tall trees if one was taller. In addition, due to how body mass and volume increase at a cubic geometric rate in relation to height/ vertical increases, that meant that taller creatures would be literally bigger in size, due to correct proportions.

For many mammals, but especially primates, the male of the species is the larger of the two sexes as well as being stronger in terms of brute force. From what we learn in evolutionary psychology and evolutionary biology, we can say that certain males were alpha and others were beta. I would propose that on average not only did alpha male humans have more testosterone, they were also bigger, specially taller. This meant that they had far more access to mating partners than beta partners. In this brutal sense, the genetically weak and who did not gain the genetic lottery had their genes weeded out of existence. If the practice continued over the subsequent generations, they offpsring in each new generation would get progressively slightly larger.

I am almost positive that in many ancient human societies and tribes, height was as prized and desired as today, if not more. It helped in the human to huma interactions as well as in fighting and sexual competition. I would say that in a synergically way eventually the females also started to choose the taller, bigger male. If this is the case, then we can probably say that in some smaller groups and tribes, where there was few viable options, many tribes people would choose to only mate with the biggest. This is what is known as intentional or selective breeding. Another term is eugenics.

If the ancient societies and tribes purposely pracices eugenics to have taller and more intimidating offspring, it would be over just a few centuries lead to some tribes being very tall in stature. However the thing that would probably cost these tribes is high levels of inbreeding cause from the desire to mate only with people of large sizes, which might mean there was only a few families who did carry such traits forcing them to mate within their own family to keep the genetic advantage, not realizing that they are actually hurting their genetic advantage.

We have many stories by naive americans and most societies in the world about groups of people who were true giants. There have been many skeleton unearthed in different regions of the world which show them being 8-10 feet tall. I suspect the stories about giants are true since it is extremely conceivable that there have been at least a few tribes which focused solely on gaining dominance by using selective breeding to gain the size they wanted.

One of the best examples is the story of the famous Irish giant from the 19th century. He had a pituitary problem causing him to be big but it turned out the pituitary condition had a genetic cause and it would turn out tow of his male cousins also developed overactive pituitaries causing them to swell up in size. If this was ancient times, certain females would choose only to mate with them, causing more pituitary giants and shifting the anthropomorphic measurements in a small town or tribe to completely shift. Another good example was that two of the 3 cases of giants who resulted from the lack of estrogen alpha and/ or beta receptors in their growth plates were the result of a consanguine union (cousin marrigage). The both would turn out to be sterile having extremely low levels of sperm count with almost everything else funcioning fine. If they had been also been non-sterile, their mating chances would increase by a lot in ancient times due to their size, and they would be selectively chosen to have more children than other men, even if they are resulted from consanguinity which should have hurt them genetically but didn’t, due to random chance.

So, just a food for thought.

The podcast series is coming along and this episode was to get out the message to people who might not have found out the website from searching or Google but through podcasts. It has a message which shows why I believe the venture and project to find a way to increase our height is a worthy goal.

Episode #4: Manifesto On Why Height Increase Is High Value And Worth Researching

I wanted to show that in terms of the businesses, ventures, projects, and ideas that are in the world today, few have the type of impact and can reach the type of basic and most universal level as trying to achieve the goal of becoming taller and bigger than who we are.

People always talk about growth in terms of the mental, emotional, spiritual, and financial but what about speaking about growth in the most basic level, the physical? Is not the desire to get slightly closer to the stars and heavens a part of man’s basic desires?

Normally I just wing it and speak from the mind but today I wanted to try something else and read out the entire episode from a transcript. I noticed that overall the speaking style was very rigid and non-fluid. Yikes! I’ve learned my mistakes and will avoid that awkwardness for future episodes.

Click Here to Subscribe via iTunes and/or leave a review for the podcast!

Note: For a transcript of the episode in PDF format, click HERE.

Length of time: 19 min

Listen Here – (to download, right click and ‘save’)

In my searching for the right type of piezoelectric material to be added to the LSJL device, something else I found from the Wikipedia article on piezoelectric material was that piezoelectric materials have been used in surgery.

From the Wikipedia article…

Surgery

A recent application of piezoelectric ultrasound sources is piezoelectric surgery, also known as piezosurgery.^[34] Piezosurgery is a minimally invasive technique that aims to cut a target tissue with little damage to neighboring tissues. For example, Hoigne et al.^[35] reported its use in hand surgery for the cutting of bone, using frequencies in the range 25–29 kHz, causing microvibrations of 60–210 μm. It has the ability to cut mineralized tissue without cutting neurovascular tissue and other soft tissue, thereby maintaining a blood-free operating area, better visibility and greater precision.^[36]

Me: What this seems to suggest is that piezosurgery has been shown to be able to make very precise, small distractions in bones without effecting the muscles or blood vessels around it. At this point the idea is only a thought. However let’s see what other things we can find from google and PubMed…

From the Wikipedia article on Piezosurgery…

Piezoelectric surgery, or piezosurgery in short – is a process that utilizes piezoelectric vibrations in the application of cutting bone tissue. The process was developed by Tomaso Vercellotti ^[1] and has been patented.^[1] It is indicated for use in oral, maxillofacial, cranial and spinal procedures.

By adjusting the ultrasonic frequency of the device, it is possible to cut hard tissue while leaving soft tissue untouched by the process. The ultrasonic frequency is modulated from 10, 30, and 60 cycles/s (Hz) to 29 kHz. The low frequency enables cutting of mineralized structures, not soft tissue. Power can be adjusted from 2.8 to 16 W, with preset power settings for various types of bone density. The tip vibrates within a range of 60–200 µm, which allows clean cutting with precise incisions. A recent article on the topic of piezoelectricity has named Piezoelectric surgery as one of the most important applications of this concept, in addition to the trivial medical ultrasound imaging. ^[2]

Me: What we are seeing is what I speculated was possible after I did the research on the extracorporeal shock wave therapy. We saw that LIPUS (low intensity pulsed ultrasound) could lead to fracture healing, and that the ESWT has a potential to be better since the frequency was higher. This was what made me wonder what would happen to bone if we just increased further either the intensity (magnitude) or frequency in say sound waves or any type of device that can release vibrations at a high level. It seems that Piezosurgery is exactly what happens. The extremely high frequency of the surgery application causes bone material to easily break apart upon contact. The cuts made are very precise.

From one of the cited articles (source)….

Abstract