This Non-Available Prodrug Taken Orally Helps Older Adults Become Taller

This Non-Available Prodrug Taken Orally Helps Older Adults Become Taller

Older Adults Become TallerI am very happy with the results of the former post  “This Non-Prescription Supplement Has Been Scientifically Proven To Make You Grow Taller Even With Closed Growth Plates“. The reaction that it received was what I was sort of hoping for and so far, it has had over 50,000+ views already. Since that post was so popular, I wanted to do a 2nd post which shows them another compound which we have found which have a similar ability.

This compound is known as a prodrug, which I am not sure how to obtain, taken orally has been shown only on a theoretical basis to increase height in the lab animals. In rats, their body lengths increased in the ways which we desire. From what I personally have read about it, I have about a 60% confidence in its ability to increase height in people who can ever get it. It would work best on adults, those people who are in theirs 30s and beyond. This suggests that this compound would indeed work for people with closed growth plates, or even specifically intended for people with completely ossified epiphyseal cartilage tissue.

So what is 2nd chemical compound which has this ability?

It is called CPA-926.

I first was informed of this particular drug in an article I had cited in one of my previous posts. This particular compound is mentioned in both the books Dynamic Reconstruction of the Spine (by Daniel H. Kim & Frank P Cammisa on pg 384) and Nonfusion Technologies in Spine Surgery. (edited by Marek Szpalsk on pg 53). I will also be referencing the medical reference “Therapeutic Strategies for Modulating the Inflammatory Diseases” edited by Barry M. Weichman but not as much as the other two.

There was also a few articles I had to glance over (notice I used the word glance, and not study) which validated this idea that the prodrug could indeed work.

It seems that this compound is both anti-tumorogenic and anti-inflammatory, which are always positives for almost any compounds we ever intend to swallow.

The most important study is the one done by Okuma.

Esculetin CPA-926Okuma M, An HS, Nakagawa K, Akeda K, Muehleman C, Masuda K (2005) Oral administration of esculetin prodrug inhibits intervertebral disc degeneration in the rabbit annular needle puncture model. Orthopaedic research society meeting, (p 370)

This particular article was published in The Spine Journal back in Sept 10, 2004 (volume 4 or 5).

We are not sure if there is a PubMed study link to it but the title of the study is located and scattered around Google just from a quick search.

From a quick look, it seems that even one patent referenced this method on how to treat discs that are degenerating.

For more proof that this idea of inhibiting the loss of disc, we refer to the patent “Method for inhibiting fibrocartilage degradation (WO 2005091960 A2)“ by Koichi Masuda, a director of Orthopaedic Surgery. (His Curriculum VItae is Available Here). I never did look over the patent extensively but did glance over the document to mine a few interesting facts about CPA-926.

  1. The compound is provided by Kureha Chemical Ind., Co. Ltd., Tokyo Japan or Kureha Chemical Corp
  2. Following the lateral X-rays of the lumbar spine, the vertebral body height and disc height of the IVDs were measured
  3. Oral administration of CPA-926 preserved disc height and the histological analyses of these tissues show that CPA- 926 protects against disc degenerative chances in a rabbit model

At this point, it might not be possible to call up the sales people at Kureha and get them to ship a few grams of this cartilage regenerative chemical compound. I haven’t tried it but is only providing evidence of its efficacy.

In terms of how effective this chemical compound could be, it could be similar to Harpagoside, which I wrote about in the old post “Increase Height and Grow Taller Using Harpagoside“

So does this mean that every single compound which has inhibitory effects on compounds which have catabolic effects on cartilage (aka treats osteoarthritis) is good?

If we were to be completely general, I would give a tentative yes to that question. While there is probably a few dozen compounds the drug synthesize makers know of which have abilities to treat diseases associated with articular cartilage degeneration, very few of them have shown the characteristic of doing more than just preventing degradation, but also anabolic effects, where cartilage is regrown back. This prodrug of the chemical compound 6,7-dihydroxycoumarin suggests that it has those anabolic effects besides just the usual inhibition of catabolic processes in the IVDs.

Is it however better than just popping Glucosamine Sulfate?

We are not sure about the comparison but it is obviously harder.

Is it safe to take orally?

From the 3-4 main studies that have talked about this compound, it has been found to be safe on the lab rats and lab rabbits it was tested on.

So we buy this from somewhere?

I have not searched to see whether the Keruha Chemical Corp in Tokyo sells this stuff.

The Inhibitory Effects Of CPA-926 On The MMPs

On multiple posts written by Tyler over the years, he mentions over and over again how the MMPs (aka Matrix Metalloproteinases) are not good for height increase, specifically MMP-9 and MMP-13. My own research supports this opinion. The study by Yamada and even Watanabe (Esculetin suppresses proteoglycan metabolism by inhibiting the production of matrix metalloproteinases in rabbit chondrocytes.) suggests that for esculetin at least and whatever derivatives that is made from it (or a precursor to the compound) shows that the main way these compounds work is by targeting the pathways of the MMPs.

For the Future

I am also looking into three other compounds called RO 32-3555 (aka Trocade), SKI 306X and KHBJ-9B, which seems to have similar properties in being anti-inflammatory and great for prevention of cartilage degeneration. Those reports will be delivered on another day.

Study shows feasability of micro-growth plates

The idea of LSJL is to create microgrowth plates via fluid shear strain on the mesenchymal stem cells in the bone marrow.  This study shows that microgrowth plates can exist:

Growth Plate Regeneration Using Polymer-Based Scaffolds Releasing Growth Factor

“Depending on the type of growth plate fracture and the severity it can lead to stunted bone growth or bone growth deformation. The current treatment options for growth plate fracture are removal of the bony bar and replacing it with a filler substance, such as, bone cement or fat, but still yield poor results 60% of the time. In previous work, poly(lactic-co-glycolic acid) (PLGA) scaffolds were developed and studied in vivo for the purpose of growth plate regenerationDepending on the type of growth plate fracture and the severity it can lead to stunted bone growth or bone growth deformation. The current treatment options for growth plate fracture are removal of the bony bar and replacing it with a filler substance, such as, bone cement or fat, but still yield poor results 60% of the time. In previous work, poly(lactic-co-glycolic acid) (PLGA) scaffolds were developed and studied in vivo for the purpose of growth plate regeneration”

micro growth platemicrogrowthplate

“Figure 6.7. Fat implant showed thin, continual line of cells across medial side that contained reserve (R), proliferative (P), hypertrophic (H) cartilage cells and calcification zones (C).”

Another micro growth plate:

microgrowth plate2

“Blank scaffold on (A) the lateral side with columnar structure and (B) the medial side with the appearance of stacked (S), reserve (R), proliferative (P), and hypertrophic (H) cartilage cells.”

Here’s a growth plate but loaded with IGF-1 so it’s much more sophisticated:

igf1 microgrowthplate

“IGF-I loaded scaffold showed dispersed pockets of cartilage cells throughout the medial side with the appearance of reserve (R), proliferative (P), hypertrophic (H), and degenerative zones (D).”

“In this study, the attempt to regenerate the growth plate did not result in columnar structure to the degree that the native growth plate has, regardless of the treatment type. It appeared that the fat implant allowed for some cartilage regeneration, but it was only a cell wide at most points and most of the chondrocytes were in the calcification zone. The tissue surrounding the cartilage areas was woven bone, which has been known to appear after fractures{But would this still result in a longer bone?}. The blank scaffold treatment resulted in tissue having a similar structure to that for the fat implants with a couple exceptions. First, there were a few areas where blank scaffolds had been placed with some cellular stacking, and secondly, the lateral side retained more structure, resembling that of the native growth plate, compared to defects treated with fat graft. The blank scaffolds gave the epiphyseal region more structural support, preventing further collapse of the lateral growth plate, while the fat graft implant had a thinner growth plate region across the whole tibia.”

“The defects treated with IGF-I-loaded scaffolds, both with or without seeded cells, showed a similar appearance on the lateral side as that of the blank scaffold group, however the medial sides were quite different. Without cells, the IGF-I-loaded scaffold resulted in pockets of chondrocytes throughout the medial side along the epiphyseal line that contained cells in all zones of cartilage development. The addition of cells created a large vertical pocket (~3 mm long) of chondrocytes located in the upper epiphyseal region. Interpretation of the IGF-I loaded samples was limited because only one sample could be used for observation so it is difficult to say if this cellular organization would occur again. The cells were mostly in the hypertrophic state and had no columnar organization. Both types of IGF-I loaded scaffolds (with and without cells seeding) increased the density of hypertrophic chondrocytes compared to the fat, blank, and hybrid scaffolds. Cells seeded on scaffolds containing IGF-I created the largest population of chondrocytes”

“Though the results did not show total growth plate regeneration, the necessary cell types were present”

It should be noted the mesenchymal stem cells used in this study were harvested from the diaphysis thus providing evidence that MSCs needed to create growth plates do not necessarily have to be from the Zone of Ranvier.

The study did not display changes in length due to the various scaffolds.  The fat scaffold and IGF-1 seeded scaffold did reduce the angular measurement resulting from part of the growth plate being damaged.  The blank scaffold altered the angular measurement disparity but increased it in the tibia and decreased it in the femur.  We can be fairly certain that microgrowth plates can alter longitudinal bone growth as the angular measurement is dependent on how tall one side of the bone grows versus the other.

Even though this study involves scaffolds and LSJL does not.  The information about microgrowth plates altering height growth can be extrapolated to LSJL as MSCs could migrate to the epiphyseal region and use bone as a natural scaffold.

This study provides evidence that you don’t need to create a whole growth plate to increase height.

Can rest intervals make LSJL more effective?

Enabling bone formation in the aged skeleton via rest-inserted mechanical loading.

“The mild and moderate physical activity most successfully implemented in the elderly has proven ineffective in augmenting bone mass. We have recently reported that inserting 10 s of unloaded rest between load cycles transformed low-magnitude loading into a potent osteogenic regimen{but is it a chondrogenic regimen?} for both adolescent and adult animals. Here, we extended our observations and hypothesized that inserting rest between load cycles will initiate and enhance bone formation in the aged skeleton. Aged female C57BL/6 mice (21.5 months) were subject to 2-week mechanical loading protocols utilizing the noninvasive murine tibia loading device. We tested our hypothesis by examining whether (a) inserting 10 s of rest between low-magnitude load cycles can initiate bone formation in aged mice and (b) whether bone formation response in aged animals can be further enhanced by doubling strain magnitudes, inserting rest between these load cycles, and increasing the number of high-magnitude rest-inserted load cycles. We found that 50 cycles/day of low-magnitude cyclic loading (1200 microepsilon peak strain) did not influence bone formation rates in aged animals. In contrast, inserting 10 s of rest between each of these low-magnitude load cycles was sufficient to initiate and significantly increase periosteal bone formation (fivefold versus intact controls and twofold versus low-magnitude loading){we’re not looking for periosteal bone formation, we’re looking for neo-growth plate formation but the principles may be the same}. However, otherwise potent strategies of doubling induced strain magnitude (to 2400 microepsilon) and inserting rest (10 s, 20 s) and, lastly, utilizing fivefold the number of high-magnitude rest-inserted load cycles (2400 microepsilon, 250 cycles/day) were not effective in enhancing bone formation beyond that initiated via low-magnitude rest-inserted loading. We conclude that while rest-inserted loading was significantly more osteogenic in aged animals than the corresponding low-magnitude cyclic loading regimen, age-related osteoblastic deficits most likely diminished the ability to optimize this stimulus.”

“While the inability to perceive mild and moderate loading events as stimulatory may reflect potential deficits in numbers and/or viability of mechanosensory (e.g., osteocytic) cells, the inability to initiate and, especially, sustain bone formation more likely reflects potential for deficits in the numbers and/or function of osteoblastic cells. Additionally, the declining availability of biomolecules involved in coordinating and enhancing osteoblastic response to mechanical stimuli (e.g., TGF-β, IGF-1){these biomolecules are involved in chondrogenesis too so it’s important to monitor changes in these biomolecules due to aging} potentially compromises the ability of bone cells in aged tissue to perceive low and moderate magnitude loading events as being stimulatory. Last, the age-related decrease in the surface to volume ratio of bone mineral matrix and increased viscosity of interstitial fluids could decrease biophysical stimuli delivered to bone cells via standard exercise regimens{this could affect neo-growth plate formation too as the degree of biophysical stimuli delivered to cells would affect the ability to form new growth plates}”

“A total of 49 aged female C57BL/6 mice (mean ± SE; 21.5 ± 0.16 months)”

“The device fixes the proximal tibia (at the tuberosity) against motion and applies controlled loads to the distal tibia, thereby placing the tibia diaphysis under “cantilever” bending in the medial–lateral direction.”<-not quite like LSJL.

“a strain versus load calibration curve was determined and yielded peak strains in the range of 800–2400 με at the periosteal surface (and 600 to 1800 με peak strains at the endocortical surface) for loads of 0.4–1.2 N, respectively.”

“rest-inserted loading (particularly at low magnitudes) enhances rates of bone formation by primarily increasing mineral apposition rates compared to cyclic protocols”

“attempts at further enhancing the bone formation response to rest-inserted loading by doubling strain magnitude, inserting rest-intervals, and subjecting animals to five-fold the number of high-magnitude rest-inserted loading cycles were all ineffective in the aged skeleton.”

Chondrodiatasis Is Tensile Loading The Epiphyseal Growth Plate Cartilage Longitudinally Without Fractures

Chondrodiatasis Is Tensile Loading The Epiphyseal Growth Plate Cartilage Longitudinally Without Fractures

ChondrodiatasisFor a long time I’ve wondered whether it was possible to do more than just stretch out the bone tissue to make the overall bones longer, and it seems that there have been a few recent articles which came out showing that it is indeed possible to stretch out cartilage (epiphyseal growth plate) tissue. More than just stretching the cartilage, it seems that it would not even result in any type of fractures.

This medical technique is known as chondrodiatasis. It seems that it is so rare and so uncommon that there is almost no information on it except in a few sources from Google. Even orthopedic surgeons are not that too familiar with this idea. (There is a 2nd type of physeal distraction called distraction epiphysiolysis which is much faster but does result in fractures and the cartilage ossifying by the trabecular bone tissue).

In the medical reference book “Musculoskeletal Tissue Regeneration: Biological Materials and Methods“ by Vacanti and Pietrzak there is a small section dedicated to alternative ways to distract bones which is much less step intensive.

There are two types. You have…

1. Distraction Epiphysiolysis – This method is the distraction of the growth plate at a fast rate of 1-1.5 mm per day. The fast rate of separation between the epiphysis and metaphysis results in the cartilage developing fractures, which also leads to the physeal cartilage to turn into trabecular bone. The experiment done by Zavialov and Plaskin back in 1967 showed the change of the cartilage into bone. We won’t focus on this type of physeal distraction technique too much because of the fact that the cartilage is almost immediately converted into bone through advanced levels of osteogenesis.

2. Chondrodiatasis – This is the type of physeal distraction that would be worth our time to look at. It is very slow in fact, usually less than 0.5 mm a day. It seems that tension stress causes the chondrocytes to increase in activity. This technique also increases the level of osteogenesis but there is no evidence (yet) that the cartilage will convert into bone tissue.

Sliedge and Noble back in 1978 showed that they could increase the thickness of lab rabbit’s growth plates by 150% without the presence of fractures. De Bastiani distracted it at just 0.25 mm a day and the chondrocytes cells went through hyperplasia but the overall form of the cells did not seem to change. When the rate of longitudinal growth after physeal distraction was checked, there was no decrease in bone longitudinal growth seen.

Remember however that for any type of bone or cartilage distraction, the surgeons would still drill two pin holes into the bone to pull. It seems that there is no way to get away from having an external fixator used.

However, there will always be complications associated…

Surgical Complication #1: Because we are talking about the growth plates, which are often already so thin, to distract them by only 0.25 mm a day would be very hard to perform.

Surgical Complication #2: The physis would actually get damaged.

Surgical Complication #3: This is the major issue, which seems to be many incidences where growth of the bones seemed to completely stop, which is slightly concerning.

Out of the three ways that you can distract a bone, both of the ways to distract cartilage has proven to be not that effective. That is why the surgeons have almost always just focused on callotasis, instead of these two other types of surgical techniques.

Surgical Complications

Looking through the PubMed archives, there were probably only a dozen studies which ever mention this term “Chondrodiatasis“. We picked the ones which are worth looking over and linked them below…

  1. Chondrodiatasis-controlled symmetrical distraction of the epiphyseal plate. Limb lengthening in children.
  2. Early physeal closure after femoral chondrodiatasis
  3. A large-deformation, finite-element study of chondrodiatasis in the canine distal femoral epiphyseal plate

We will also make a medical reference to the text “Physeal Injury Other Than Fracture” By Hamlet A. Peterson.

While the initial studies showed us that maybe it is possible to lengthen a bone by distracting the epiphyseal cartilage, which would mean no osteotomy necessary, these later studies showed that maybe it is not such a good idea.

The first study gave us hopes and showed that the surgical technique might be viable. There was no visible lesions, infections, or loss in vascularization.

It is the 2nd study which showed that this technique did have its own share of problems. It seemed that when the bone lengthening was done, almost immediately after the surgery was over, the cartilage ossified over. The end result was that the lengthen bone actually shrank. The end result was that this type of surgery was not recommended for children who are too young or have just a small limb length discrepancy.

The last study done on the femoral growth plates of lab dogs was not as informative as I hoped. All it showed that was if you are going to be pulling the bone, the cortical bone and the area where the cartilage and the bone touch will experience a high level of stress.

Conclusion

These procedures known as Chondrodiatasis and Distraction Epiphysiolysis are not well known because they are probably almost never done anymore. It seems that the amount of complications where the cartilage will ossify to prematurely was the reason most orthopedic surgeons will not try to length bones by doing distraction on the cartilage. Distracting the bone tissue seems to be much less complicated and more straight forward, with much more surgical evidence and examples.

Triptorelin Can Increase Adult Height For People Developing Precocious Puberty

Triptorelin Can Increase Adult Height For People Developing Precocious Puberty

Someone recently messaged me information about the existence of a type of drug called Triptorelin which is used by endocrinologists to help young children develop taller adult height. It did trigger my interest so I did only a little bit of research on this drug and these are 5 sources which had the most relevance to the effects of triptorelin on growth.

  1. Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. French study group of Decapeptyl in Precocious Puberty
  2. Final height and timing of menarche after treatment for idiopathic central precocious puberty (CPP)
  3. My daughter & Triptorelin (Decapeptyl 3.75mg)?
  4. Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty
  5. Effect of GnRH Analogs Leuprolide-Acetate and Triptorelin on Bone Mineral Density in Girls with Central Precocious Puberty

The basic idea is that for a minority of females, they will experience something known as central precocious puberty aka CPP. The gonads will start releasing their steroids about 2-3 years earlier than was they are supposed to. The ultimate result is that the girls will end up with shorter than average final adult height. To inhibit the gonads of the female, the egg, from releasing too much of the steroid, which I believe is just estrogen, the medical researchers used this compound called Triptorelin.

We learn from the 2nd PubMed study that two groups were made, the control group and the group with the girls that were given the treatment. The dosage and timing was every 4 weeks at a dose of 3.75 mg. It was shown that the triptorelin could hold back the initiation of menarche by almost 1.4 years, when the experimental and control groups were compared. What is surprising with the 2nd study is that the average heights of the two groups tested had only about a 2.3 cm difference, which the researchers felt was statistically insignificant.

As for the 1st study, it was probably more insightful. The study was tested on both girls and boys. The Final Height aka FH was compared to control groups and what the predicted final adult height of the control groups would be. For the girls, the average difference was around 4.8 cm but the range of the differences was extremely large (even over 10 cm for certain subjects in the group). For the boys, the increase in height was even more noticeable. Of course, they were compared to the group of kids who did not get any type of GnRH Agonist treatment. Compared to the the predicted height before treatment, the actual increase in height was on average exactly where the predict height was calculated to be.

What is probably most interesting is that apparently triptorelin can actually have a detrimental effect if the treatment is given after a certain age, specifically about at age 11 for the girls. 

Beyond these few studies, there are commercial viability in the drug for children who are noticeably shorter but have not gone through puberty yet. The company called Debiopharm Group has been working on the drug. The website for Debiopharm Group which showed that…

January 13, 2014 – Debiopharm Group™ (Debiopharm), a Swiss-based global biopharmaceutical group of companies with a focus on the development of prescription drugs that target unmet medical needs and companion diagnostics, announces that it has completed the recruitment of patients for its Phase III clinical study in Central Precocious Puberty (CPP) with triptorelin 22.5 mg.

My personal opinion is that while triptorelin may be useful, we maybe should look into the dozen other compounds we have already found which is probably more effective in inhibiting the stunted growth in children. Triptorelin is not the best compound to use since its effects is very depend on the age of the kid for when they start getting the treatment.

For us, as adults, this type of synthetic compound, which is a type of GnHR agonist, is not useful. If it is going to be successful in some type of effect, you want to start on it as early as possible, and quit using it around the age of 12.0-12.5 years of bone age. The source of this info was from the study “Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty“

Restoring Lost Height From IVD Collapse Is Already Possible But What About Healthy Thick Discs?

Restoring Lost Height From IVD Collapse Is Already Possible But What About Healthy Thick Discs?

Restoring Lost HeightEver since I put up the contact us button to the sidebar which is linked to our contact us web page the amount of messages and information that is reaching the website email has increased 5X. With most of the messages, the readers of the website have really found some amazing resources which prove some concepts which we suspected was being done already.

In the past, we’ve found multiple patent proposals on how it would be possible to restore the lost height people have after suffering something like a bulging disc or herniated or had their discs crushed by the amount of mass that on the upper torso of the body. We all know that over time, as people get older, they usually loss height. Having any type of medical condition which affects the back (or more specifically the lower back like the L4-L5 region) can make the height lost much greater.

I personally have read a few forum threads around the internet where people loss even upwards of 1.5-2 inches after developing a serious back problem like kyphosis, which is hunched back. Of course, it could be even worse than just 2 inches.

If their is a medical cause making the person loss height from disc degeneration, there are now multiple ways to treat that and restore height. I list the following articles and sources that the people who have messaged us have given us…

Source #1: New stem cell transplant holds promise for treatment of degenerative disc disease

Senior author, Wenchun Qu, MD, PhD, of the Mayo Clinic in Rochester, Minnesota – stem cell therapy for disc degenerative disease might be a potentially effective treatment…. not only did disc height increase, but stem cell transplant also increased disc water content and improved appropriate gene expression…. prepare for translation of stem cell therapy for degenerative disc disease into clinical trials….The increase in disc height was due to restoration in the transplant group of the nucleus pulposus structure, which refers to the jelly-like substance in the disc, and an increased amount of water content, which is critical for the appropriate function of the disc as a cushion for the spinal column, the researchers concluded.

Source #2: Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma

Here are excerpts of the abstract which we just copy and pasted below….

An ex vivo degenerative intervertebral disc (IVD) organ culture system… a stem cell and growth factor-based therapeutic approach for the amelioration of IVD.

…different therapeutic regimens including: (1) mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), (2) platelet-rich plasma (PRP) and (3) MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model…. Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased…

PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation…. repeated and supported by in vivo porcine degenerative system.

Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups

Source #3: Molecular and genetic advances in the regeneration of the intervertebral disc

Rapid advances… have resulted in several promising methods to facilitate the translation of laboratory-based techniques to clinical disc regeneration…. Tissue engineering strategies that employ (1) biomimetic scaffold materials, (2) differentiation-driving bioactive molecules, and (3) multipotent cells to enhance disc regeneration are being developed at a rapid pace.

The paper was not one of those papers written to say something new, but to organize all the possible ways that the current medical community knows how to restore the discs. Here was a list of the ideas that tissue engineering researchers around the world have tried…

1st Approach:  Disc Regeneration Via Morphogens and Mitogens

  1. Delivery of exogenous proteins: Growth factors and cytokines
  2. Factors with biologic activity: Mitogens, morphogens, and intracellular mediators (ex. TGF-Beta1, TGF-Beta3, IGF-1, etc)
  3. Transforming growth factor beta superfamily; morphogens and biologic mediators of intravertebral disc development
  4. In-vitro (and In-Vivo) study of BMP-2 for IVD regeneration
  5. BMP-7 (aka OP-1) induces similar in vitro effects as BMP-2 in IVD cells
  6. In vitro and in vivo studies of BMP-14 (GDF-5)
  7. More work is needed to ascertain effects of lesser known bone morphogenetic proteins family members (like BMP-4 and BMP-13)

2nd Approach: Cell-Based Regenerative Strategies

  1. MCSs
  2. MCSs from bone marrow which can differentiate into nucleus pulposus like phenotype
  3. In vivo experimentation demonstrates the promise of marrow-derived mesenchymal stem cells
  4. Multiple niches of mesenchymal stem cells display regenerative properties

3rd Approach: Intervertebral Disc-Derived Cells

  1. Cells derived from intervertebral disc… rejuvenate endogenous cells
  2. Notochordal cells

4th Approach: Advances in Gene Therapy and Delivery

  1. Altering genotype of cell population, transcription/translation sustains protein synthesis
  2. Direct in vivo gene therapy: Direct administration of infecting agent(s) to host
  3. Adenoviral vectors expressing numerous bone morphogenetic proteins
  4. Sox9 gene delivery in human IVD cells
  5. Primary human IVD cells respond favorably to adenoviral infection with growth factors
  6. Treatment of IVD cells with lim mineralization protein-1 causes increased production of proteoglycans both in vitro and in vivo

5th Approach: Multi-Faceted Approaches to Disc Regeneration

  1. In vivo performance of cell-seeded scaffolds

6th Approach: Hydrogel-Based Scaffolds: A Promising Method for Nucleus Regeneration

  1. In vivo growth factor delivery from scaffolds

7th Approach: Enhancing Disc Regeneration by Slowing The Degenerative Process

  1. Proteinase inhibitors utilized in gene therapy-based approaches
  2. Statins act as intracellular inhibitors of MMP production and enhance BMP-2 mRNA expression
  3. Lactoferricin causes increased PG accumulation and downregulated catabolic processes
  4. TNFα-stimulated gene product TSG-6 with inter-α-inhibitor downregulate MMP activation
  5. Etanercept is an approved TNF-α inhibitor
  6. The oral administration of CPA-926 an esculetin prodrug

Source #3: Duke Bioengineers Develop New Approach to Regenerate Back Discs

In a proof-of-concept study published online in the journal Biomaterials… a new biomaterial designed to deliver a booster shot of reparative cells to the nucleus pulposus, or NP — the jelly-like cushion naturally found between spinal discs. The NP tissue distributes pressure and provides spine mobility, helping to relieve back pain.

  • Primary Goal: “Our primary goal was to create a material that would be liquid at the start, gel after injection in the disc space and keep the cells in the location where they’re needed,”
  • Secondary Goal: “Our second goal was to create a material that would provide the delivered cells with the environmental cues to promote their persistence and biosynthesis.”

The most common types of problems: …re-implanting NP cells, or even stem cells, can delay disc degeneration. Several companies already offer cell delivery strategies, but the methods are poor and ineffective. (using the currently available cellular delivery strategies, 100 percent of the injected NP cells leak out of an IVD site within three to four days after injection. ) “They allow the cells to quickly migrate out of and away from the injection site,” Francisco said.

The Duke team’s delivery strategy keeps the cells in place and provides cues that mimic laminin, a protein in native nucleus pulposus tissue. Laminin is normally found in juvenile but not degenerated discs and allows injected cells to attach and remain in place with the delivered biomaterial. Laminin may also enable the cells to survive longer and produce more of the appropriate extracellular matrix or structural underpinning of the discs that help stop degeneration, Setton said.

The researchers… developed a gel mix designed to reintroduce NP cells to the intervertebral disc (IVD) site. The gel mixes together three components:

  1. the protein laminin-111 that has been chemically modified
  2. two polyethylene glycol (PEG) hydrogels that can attach to the modified laminin.

Separately, these substances remain in a liquid state. The gel, however, holds the cells in place upon injection.

What they did: ….injected the gel into rats’ tails… puncturing the tail’s thin outer layer, they held the needle in place for one minute, delivered the injection to the rat’s IVD site, and closed the injection spot. The solution began to solidify after five minutes and was completely set at 20 minutes.

The Result: …more than 14 days after injection significantly more cells remained in place when delivered within the biomaterial carrier compared to cells delivered in a liquid suspension.

“The concept is that these cells will be promoted to produce matrix that can support tissue regeneration or arrest degeneration,” Setton said….

The exact study that the article above refers to is “Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.“

Source #4: NOVOCART® DISC

is a high-quality autologous cell compound in an innovative hydrogel for the biological reconstruction of partially damaged discs following disc prolapse

Biological disc reconstruction

…biological reconstruction of partially damaged disc tissue before massive degeneration… transplantation of in vitro cultivated chondrocytes from autologous disc tissue,or ADCT (Autologous Disc Cell Transplantation).

ADCT is comparable to joint ACT (Autologous Chondrocyte Transplantation)… In both cases, isolated from the biopsy material, the cultivated cartilage cells induced the desired reconstruction.

One further special feature…is the hydrogel used, which fixes the cells in the damaged disc… also anti-inflammatory.

Description of ADCT with NOVOCART® DISC

Transplantation of the cultivated disc cells can take place three months after extraction by way of operation of the prolapsed disc. The relatively long period between tissue extraction and cell transplantation must be adhered to, to ensure that the protective fiber ring (annulus fibrosus) is fully healed following the intervention.

So what do these 4 sources which was sent to us suggest?

We know that there are at least 2 different research teams at universities which are doing research to figure out how to restore the function and shape of IVDs after they have suffered through discs degeneration, whether due to just normal old age or some type of degenerative disease.

Since these teams are able using whatever technique to restore the shape of the IVD, they have also increased the thickness, which translates to mean that the person regained lost height.

Whether it is a scaffold implant, or cells like MSCs, or growth factors, the discs can be saved and given new life.

The first point is this – We now have multiple options on how to restore lost height from the collapse of the IVDs.

However, can we do anything if the discs are healthy and we want to increase our height?

I suspect that for most people, we are not fully maximized on how tall we can be. The majority of people would be able to gain upwards of even 1.25 inches in extra height, if we can correct our posture, and then our IVD structural integrity. If we wanted to, we could use these developing technologies to make sure that our nucleus pulposus matrix is strong and rich in the right collagen material.

However, there are a small group of people who have the discs already full. Maybe we are 18-20, with a completely healthy body but our only problem is that we suffer from familial short stature. For these people, who have already done all the stretching, the disc decompressions, and maybe tried even certain traction machines, I would suggest that we would no longer focus on the discs, but to focus on the material next to the discs.

However, the problem is probably going to have more to do with medical ethics than a technical problem. Most doctors would never agree to sticky a needle into the spinal area of a healthy young adult. There is a great fear that a needle stuck in the wrong area would cause a disc to become punctured or even slight paralysis.

In a rather old post I did, it was shown that for young adults, around the 17-23 range, many of them have a very thin layer of articular cartilage that does run between the bone tissue of the vertebrate bone and the nucleus pulposus of the discs. That layer of cartilage however is so thin that it is very hard to see. It was guessed that the layer is most likely about 1-2 mm thick. However, we can work with that.

If might be possible to stimulate that layer of articular cartilage to go through hypertrophy using a small injection of IGF-1 directly into the cartilage tissue. We know that a local injection of IGF-1 into the bone layer under the periosteum would increase the rate of long bone longitudinal growth, as we had revealed in a previous post “Increase Height And Grow Taller Using Local Subperiosteal Injection Of Growth Factors IGF-1 And TGF-Beta Percutaneously” as long as the epiphyseal growth plate cartilage was intact.

Since the young adult who wants to grow taller, but has full discs, still has maybe 1-2 milimeter of cartilage in every connecting segment between the discs and the vertebrate bone, it should be reasonable to inject the IGF-1 (or TGF-Beta) locally next to the layer of thin articular cartilage. Since there is 33 vertebrate bones in the human skeletal system, we probably have 20 or so thin layer of cartilage we can try to stimulate using small needles.

If we can use an X-ray to double check the location of the needle injections, to make sure that we don’t puncture a disc or hit a nerve ending, it could work. The hypertrophic effect of injections of the growth factor into 20 of these thin layers can add up to maybe 2-3 extra inches, but that is a very wildly optimistic situation.