Monthly Archives: March 2014

Using chondrocyte hypertrophy to grow taller via articular chondrocytes?

It’s been established that the fingers can grow longer after cessation of development.  One primary difference of the fingers and the bones of say the legs is that there’s periosteum covering the articular cartilage of the legs and not of the bones of the fingers.  One issue of articular chondrocyte hypertrophy is it’s correlation with osteoarthritis(and).

Chondrocyte hypertrophy in skeletal development, growth, and disease.

” Chondrocyte hypertrophy is an essential contributor to longitudinal bone growth, but recent data suggest that these cells also play fundamental roles in signaling to other skeletal cells, thus coordinating endochondral ossification. On the other hand, ectopic hypertrophy of articular chondrocytes has been implicated in the pathogenesis of osteoarthritis.”

“Chondrocytes first differentiate from mesenchymal precursor cells after these have undergone cellular condensation{we have to be sure we’re covering this step if we want to create new growth plates}. This process, termed chondrogenesis, is characterized by expression of the cartilage master transcription factor Sox9 and induction of its target genes, for example, the classical chondrocyte markers, collagen II, and aggrecan. In a subsequent step, chondrocytes increase their rate of proliferation in a directed pattern along the developing longitudinal axis of the future bone, forming characteristic columns of clonal cells. Under tight control from endogenous and exogenous factors, these cells then withdraw from the cell cycle and start differentiating further. This differentiation step is accompanied by a large increase in cell volume, for example, chondrocyte hypertrophy. The conventional view is that hypertrophic chondrocytes represent the terminal step in this maturation process which culminates in the apoptosis of cells and replacement of hypertrophic cartilage by bone tissue. However, there have been reports about “transdifferentiation” of hypertrophic chondrocytes to osteoblasts”

“Not only is the cell volume increase during hypertrophy a major contributor to longitudinal bone growth, but these cells also act as signaling centers that secrete growth factors, cytokines, and other signaling molecules that can act on other cell types involved in endochondral ossification, such as osteoclasts, osteoblasts, and endothelial cells. Thus, the differentiation to this stage, as well as the behavior of differentiated hypertrophic chondrocytes, are tightly regulated by a multitude of systemic and local factors, including growth hormone, insulin-like growth factors (IGFs), thyroid hormone, parathyroid hormone-related peptide (PTHrP), Indian hedgehog, fibroblast growth factors (FGFs), canonical and noncanonical Wnt signaling, transforming growth factor-β (TGFβ) family members, C-type natriuretic peptide, and others. Within the cell, the classical mediators of these signals, such as β-catenin in canonical Wnt signaling and Smad proteins in TGFβ/bone morphogenetic protein signaling control cartilage growth, along with common kinases (e.g., MAP and PI3K/Akt) and GTPases (e.g., Rho GTPases). In the cell nucleus, Runx and MEF2 transcription factors, along with the histone deacetylase HDAC4, have been recognized as key regulators of chondrocyte hypertrophy.”

“mice lacking both FoxA2 and FoxA3 activity in cartilage display postnatal dwarfism, a result of severely impaired chondrocyte hypertrophy and mineralization shown by markedly attenuated expression of hypertrophic markers, such as collagen X, MMP13, and alkaline phosphatase”

“induction of chondrogenesis in chicken limb-bud mesenchymal micromass cultures results in increased FoxA1 and FoxA2 expression. Electrophoretic mobility shift assays show FoxA2 to bind to conserved binding sites within the chicken collagen X enhancer. Interestingly, exogenous FoxA2 can activate expression of a Collagen X-luciferase reporter gene in both chondrocytes and fibroblasts”

“HIF-2α contributes to physiological endochondral ossification by controlling chondrocyte hypertrophy, cartilage degradation, and vascularization. In particular, HIF-2α was identified as the most potent activator of the COL10A1 promoter in vitro. The expression of HIF-2α’s encoding gene, Epas1, also increased in parallel to that of Col10a1, Mmp13, and Vegf-α during chondrocyte differentiation”

“ectopic expression of Epas1 enhances cytokine-induced expression of catabolic genes necessary for cartilage breakdown. Similarly, both in vivo and in vitro models of Epas1 deficiency show protection against OA through suppression of cartilage degradation and catabolic and hypertrophic gene expression”

” HIF-2α [is a] functional inducer of the CEBPB promoter. As C/EBPβ is a transcription factor crucial for the transition from proliferation to hypertrophy in chondrocytes ”

“HDAC4 (histone deacetylase 4), which inhibits hypertrophy by suppressing the activity of Runx2 and MEF2C”

“kinase SIK3 (salt-inducible kinase 3) is essential to locate HDAC4 in the cytoplasm (and thereby relieve the inhibitory activity of HDAC4 on MEF2C and possibly Runx2). Correspondingly, chondrocytes from Sik3 KO mice show increased nuclear staining for HDAC4, resulting in delayed hypertrophy and dwarfism”

” Hdac3 KO mice showed accelerated chondrocyte hypertrophy but smaller cell size, which the authors attribute to increased expression of the phosphatase leucine-rich repeat phosphatase 1 (Phlpp1) in HDAC3-deficient chondrocytes. Increased Phlpp1 levels then suppress Akt signaling. Since the PI3K-Akt pathway is a major positive regulator of chondrocyte hypertrophy, these data suggest a direct pathway from epigenetic regulation of gene expression to cell size increase”

“Three different phases of hypertrophic cell enlargement, the first characterized by simultaneous increase in cell volume and dry mass, the second by preferential cell swelling without corresponding dry mass production, and the third again by proportional increases in cell volume and dry mass. Differences between slow and fast growing bones were due to changes in phase II and particularly phase III”

mice deficient for the key collagenase in OA, MMP13, still show chondrocyte hypertrophy in response to OA-inducing joint surgery, but are protected from cartilage degeneration“<-So it’s possible to grow taller via articular cartilage growth without cartilage degeneration.

We know that cartilage hypertrophy plays a very large role in how much bones grow longer.  There are supplements that could stimulate chondrocyte hypertrophy but inhibit cartilage degradation.  So this sort of method would be possible to test with suppelements only and not need mechanical methods. Cartilage degradation is vital though for longitudinal bone growth via growth plates so this would only work via adults past the developmental stage.

The chondrocytic journey in endochondral bone growth and skeletal dysplasia.

“Extracellular signals, including bone morphogenetic proteins, wingless-related MMTV integration site (WNT), fibroblast growth factor, Indian hedgehog, and parathyroid hormone-related peptide, are all indispensable for growth plate chondrocytes to align and organize into the appropriate columnar architecture and controls their maturation and transition to hypertrophy. Chondrocyte hypertrophy, marked by dramatic volume increase in phases, is controlled by transcription factors SOX9, Runt-related transcription factor, and FOXA2.”

“In vertebrates, the endochondral bones of the axial and appendicular skeleton develop from mesenchymal progenitors that form condensations of bipotential osteo-chondroprogenitors in the approximate shape of the future skeletal elements. These osteo-chondroprogenitors undergo lineage restriction toward either chondrocytes or osteoblasts. The primordial cartilage continues growing through recruitment of more mesenchymal progenitors and proliferation of chondrocytes. Once committed to the chondrocytic fate, the chondroprogenitors further differentiate into chondrocytes which proliferate, mature, exit the cell cycle, and undergo hypertrophy, forming an avascular cartilaginous template surrounded by a perichondrium. Mature hypertrophic chondrocytes secrete matrix vesicles which mediate cartilage calcification. At the same time, adjacent perichondrial cells differentiate into osteoblasts and secrete bone matrix, forming a bone collar surrounding the hypertrophic chondrocytes, then start to organize a periosteum and later become the shaft (diaphysis) of the bone. The primary ossification center begins to develop, with blood vessels penetrating the periosteum and gaining access to the calcified cartilage, bringing in osteoclasts/chondroclasts to degrade the cartilage. Subsequently, the osteoblasts lay down bone matrix to form trabecular bone. Gradually, the chondro-osseous junction forms, dividing the cartilage template into two ends, called epiphyses. These progressive steps of chondrocyte differentiation lead to the formation of a specialized structure called the growth plate ”

“The round chondrocytes of the RZ serve as a pool of progenitor-like cells for subsequent proliferation and differentiation. In the PZ, the round cells divide, become flattened, and organize into columns in the direction of longitudinal growth while proliferating. In the PHZ, the chondrocytes exit the cell cycle and initiate hypertrophic differentiation, characterized by the expression of Ihh (encoding the paracrine factor Indian hedgehog) and Col10a1 (encoding collagen type X). In the HZ, the size of the chondrocytes increases dramatically in the upper hypertrophic zone, and then these hypertrophic chondrocytes terminally differentiate in the lower hypertrophic zone, where the cartilage becomes calcified and is replaced with bone. The fate of hypertrophic chondrocytes at the chondro-osseous junction is controversial, with both cell death and survival being indicated”

Absence of Sox9, BMP2, BMP4, Smad4, Hif1a, and hoxd13 in MSCs all result in reduced height.  In proliferating chondrocytes loss of IHH+Gli3, Wnt5a, Wnt5b, Smad1, Smad5, Col2a1, and Acan result in reduced height.  In hypertrophic chondrocytes loss of Runx2 and Col10a1 results in reduced height.

“after cell aggregation and cluster formation, BMP signaling promotes cell–cell association through compaction of the aggregate.”

” the growth plates of different bones within the same animal grow at different rates. In part, the difference may be due to the differential duration of the G1 phase in proliferating chondrocytes, suggesting that cell cycle genes regulating G1 progression are of special importance in regulating endochondral bone growth. Progression through the different phases of the cell cycle is controlled by cyclin-dependent kinases (CDKs). The activities of CDKs are in turn regulated in many ways: (1) through the concentrations of their partner proteins, the cyclins; (2) through the concentrations of inhibitory proteins of the CIP/KIP and INK families (CDK inhibitors or CKIs); and (3) through inhibitory and stimulatory phosphorylation of various CDK residues. The principal targets of the CDKs are the pocket proteins RB, RBL1 (also known as p107), and RBL2 (also known as p130). Hypophosphorylated pocket proteins form complexes with transcription factors of the E2F family. Active CDKs phosphorylate the pocket proteins, causing them to dissociate from E2F, freeing the latter to activate target genes involved in cell-cycle progression and DNA replication. Cyclins D1, D2, and D3 are implicated in chondrocyte proliferation. The Cyclin D1 gene is a target of several paracrine factors, including parathyroid hormone-related peptide (PTHrP), IHH, and WNT5b. Mice lacking only cyclin D1 are viable but small, with a smaller PZ in the growth plate. Mouse embryos lacking all three cyclin Ds survive until about E13.5—15.5, suggesting that redundancy exists between the cyclin Ds in proliferation, and that they are regulated by different factors. RB, p107 and p130, regulate cell cycle exit and differentiation of growth plate chondrocytes. The CKI p57Kip2 is strongly expressed in terminally differentiated cells and can mediate cell cycle exit. Mice lacking this gene have short limbs and display endochondral ossification defects, as illustrated by delayed cell cycle exit and incomplete differentiation of hypertrophic chondrocytes. PTHrP and insulin-like growth factor-2 (IGF2) are reported to suppress p57Kip2 gene expression to mediate proliferation. Both IGF2 and CDKN1C (p57Kip2) are located in an imprinted locus and associated with Beckwith-Wiedemann syndrome, an overgrowth syndrome in human.”

“IHH promotes the differentiation of round proliferative chondrocytes in the resting zone into flat column-forming chondrocytes in a Gli3-dependent manner in mice”

“While IHH promotes proliferation, PTHrP delays exit from the cell cycle and initiation of hypertrophic differentiation. PTHrP represses the expression of the cell cycle inhibitor p57Kip2, and promotes the expression of the transcriptional coregulator ZFP521 and cyclin D1 to maintain chondrocyte proliferation”

“PP2A, when activated by PTHrP, dephosphorylates HDAC4, which is then translocated into the nucleus, where it inhibits the function of RUNX2 and MEF2C, and thus inhibits chondrocyte hypertrophy. Conversely, SIK3 can bind to HDAC4 and anchor it in the cytoplasm, leaving MEF2C and RUNX2 free to activate downstream targets to promote chondrocyte hypertrophy”

“Borderline chondrocytes adjacent to the bone collar may differentiate into osteoblasts{It is good for our purposes if chondrocytes transdifferentiate into osteoblasts because that means that they retain some of the chondrocyte genetic coding}. In chick explant culture, surviving hypertrophic chondrocytes undergo asymmetric cell division: one behaves as an osteoblast and may undergo further division while the other undergoes programmed cell death, leaving cell debris in the lacuna. The newly formed osteoblasts in the cartilage lacuna will be released into the chondro-osseous junction and contribute to endochondral bone formation .  Some of the hypertrophic chondrocytes look darker under electron microscopy. They are referred to as dark chondrocytes and are proposed to undergo programmed cell death inside the cartilage lacuna”

“[Hypertrophic chondrocytes] have been shown to undergo osteoblastic differentiation in situ when Sox9 is eliminated from prehypertrophic chondrocytes, displaying up-regulation of Runx2, Osx, Alpl, and Col1a1”

“In vitro, isolated chick hypertrophic chondrocytes can differentiate into osteoblasts in the presence of retinoic acid”

“[H1fa] induces collagen prolyl 4-hydroxylase expression in chondrocytes, which is necessary for generating 4-hydroxyprolines for the stability of newly synthesized collagen molecules”

Why You Need To Take Omega-3 Containing Docosahexaenoic Acid With Your Glucosamine Sulfate

Why You Need To Take Omega-3 Containing Docosahexaenoic Acid With Your Glucosamine Sulfate

In a very popular post I did last month, I had shown with very clear evidence in a randomized, double-blind study that Glucosamine Sulfate did indeed increase the height in adults with fully fused growth plates. However, the increase is not really that much. On average, the subjects (only a few dozen) averaged about 3-4 mm of height increase. My claim at the end is that for some people who combine the supplement with stretching, they can go as high as 3 cm.

Now I have found evidence that shows that for the Glucosamine Sulfate to work effectively, or even work synergistically and have an improved effectiveness, it is a good idea to mix it with another type of supplement that is easily found in any local drug store (or you buy it online).

That supplement is Omega-3.

We have already started to get emails from people saying that after taking the Glucosamine Sulphate for 8 weeks consistently, they did not notice any results. That is to be expected for most people.

For most people, the Glucosamine Sulphate, which is the closest thing we have ever found to being a magic pill, will not work. If the supplement did work, it won’t work as well as most of us hoped for. Let’s remember that the original study I showed the readers, “Effects of Glucosamine Sulphate on Spinal Height: A Randomized, Double-Blinded, Placebo Controlled Pilot Study” had been referenced in a very popular well known UK based website, TheDaily.UK

The source is valid, but the average gain was just 3 mm. That was how much I gained as well, but it took 2 weeks. 3 mm is extremely hard to notice, unless you shave your hair, and perfect your measuring practice, which I did. Yes, some people noticed gains of even 3 cms, but those cases are very, very rare. however, they do happen.

When it doesn’t work, don’t be too disappointed, since the most likely outcome is that it won’t work, for the majority of people who try it. For some people (I am guessing most likely females) there will be noticeable results.

Here is where I am going to suggest adding something with the Glucosamine Sulphate to create a much more effective oral supplement mixture. Add it with the Omega-3 Supplement.

The studies I will reference are “Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis” & “Effects of Glucosamine and Chondroitin Sulfate on Cartilage Metabolism in OA: Outlook on Other Nutrient Partners Especially Omega-3 Fatty Acids” (Did not link to them but you can google the terms to get the full study)

In the studies, the researchers noticed that the combination of Glucosamine with Omega-3 worked much better at treating the pain of osteoarthritic than just Glucosamine. There is a unique synergistic mechanism that causes the two common supplements to work together.

From a completely logical point of view, It would be wrong of me to assume that any compound that can reduce the symptoms of osteoarthritis will have potentially height increasing effects. However, it wouldn’t hurt to take at least one more supplement with the original supplement. Omega-3 supposedly is good for cognitive function as well.

I am not sure I am willing to say that orally ingesting the Omega-3 will finally give the height increase people are hoping with, but it seems to have some type of effect on the Glucosamine Sulphate which makes the effects stronger and more pronounced.

New study provides more evidence that Lithium could have height growth applications

Lithium inhibits GSK-3Beta and this next study provides evidence that inhibition of GSK-3Beta can enhance height growth.

Inactivation of glycogen synthase kinase-3β up-regulates β-catenin and promotes chondrogenesis.

“This study aimed to investigate whether inhibition of glycogen synthase kinase-3β (GSK-3β) could promote chondrocytes proliferation. The expression pattern of GSK-3β was firstly determined by immunohistochemistry (IHC) in normal mouse. Tibias were then isolated and cultured for 6 days. The tibias were treated with dimethylsulfoxide (control) or GSK-3 inhibitor SB415286 (SB86). Length of tibias was measured until 6 days after treatment. These bones were either stained with alcian blue/alizarin red or analyzed by IHC. In addition, GSK-3β and β-catenin were analyzed by Western blot. Finally, cartilage-specific GSK-3β deletion mice (KO) were generated. Efficiency of GSK-3β deletion was determined through Western blot and IHC. After treated by inhibitor SB86[the GSK-3B inhibitor], the overall length of growth plate was not changed. However, growth of tibia in SB86 group was increased by 31 %, the length of resting and proliferating was increased 13 %, whereas the length of hypertrophic was decreased by 57 %. Besides, the mineralized length was found to be significant longer than the control group. In KO mice, growth plate and calvaria tissue both exhibit significant reduction of GSK-3β whereas the lengths of tibias in KO were almost same compared with control mice. Finally, an increase amount of β-catenin protein was observed in SB86 (P < 0.05). In addition, significantly increased β-catenin was also found in the growth plate of KO mice (P < 0.05). Inhibition of GSK-3 could promote longitudinal growth of bone through increasing bone formation. Besides, the inactivation of GSK-3β could lead to enhancing β-catenin, therefore promote chondrocytes proliferation.”

It’s important to remember that growth rate does not always equal height attained due to natural development.  They also note that GSK-3B cartilage specific knock-out mice have almost the same tibia length as the control mice whereas mice that takes the GSK-3Beta inhibitor have longer tibias.  This is much more promising in regards to a supplement enhancing longitudinal bone growth as it’s much easier to ingest a GSK-3Beta inhibitor than to alter the genes on a molecular level.

Unfortunately I couldn’t get this full study.

Mechanical loading’s affect on stem cells

Previously, we learned that despite the demand for stem cells, the body did not produce more stem cells to complicate and demand greater than supply could lead to cancerous changes in the body.

Mechanical strain downregulates C/EBPβ in MSC and decreases endoplasmic reticulum stress.

“Exercise prevents marrow mesenchymal stem cell (MSC) adipogenesis, reversing trends that accompany aging and osteoporosis. Mechanical input, the in-vitro analogue to exercise, limits PPARγ expression and adipogenesis in MSC. We considered whether C/EBPβ might be mechanoresponsive as it is upstream to PPARγ, and also is known to upregulate endoplasmic reticulum (ER) stress. MSC (C3H10T1/2 pluripotent cells as well as mouse marrow-derived MSC) were cultured in adipogenic media and a daily mechanical strain regimen was applied. We demonstrate herein that mechanical strain represses C/EBPβ mRNA (0.6-fold ±0.07,) and protein (0.4-fold ±0.1) in MSC. SiRNA silencing of β-catenin prevented mechanical repression of C/EBPβ. C/EBPβ overexpression did not override strain’s inhibition of adipogenesis, which suggests that mechanical control of C/EBPβ is not the primary site at which adipogenesis is regulated. Mechanical inhibition of C/EBPβ, however, might be critical for further processes that regulate MSC health. Indeed, overexpression of C/EBPβ in MSC induced ER stress evidenced by a dose-dependent increase in the pro-apoptotic CHOP (protein 4-fold ±0.5) and a threshold reduction in the chaperone BiP (protein 0.6-fold ±0.1; mRNA 0.3-fold ±0.1).  ChIP-seq demonstrated a significant association between C/EBPβ and both CHOP and BiP genes. The strain regimen, in addition to decreasing C/EBPβ mRNA (0.5-fold ±0.09), expanded ER capacity as measured by an increase in BiP mRNA (2-fold ±0.2,) and protein. Finally, ER stress induced by tunicamycin was ameliorated by mechanical strain as demonstrated by decreased C/EBPβ, increased BiP and decreased CHOP protein expression. Thus, C/EBPβ is a mechanically responsive transcription factor and its repression should counter increases in marrow fat as well as improve skeletal resistance to ER stress.”

“The positive effect of exercise on the skeleton depends, at least partially, on the ability of mechanical input to regulate output of osteoblasts from progenitor mesenchymal stem cells (MSC){and the ability to regulate output of chondrocytes from progenitor mesenchymal stem cells}. Decreased adipocytes and increased pre-osteoblasts have been demonstrated in the marrow of running rats ”

“mechanical input applied to MSC slows adipogenesis in a process marked by downregulation of PPARγ as well as activation of β-catenin “

Review On The P3 Portable Back Stretcher From Teeter Hang Ups

Review On The P3 Portable Back Stretcher From Teeter Hang Ups

P3 Portable Back Stretcher

About a year ago I started to search online to find if there were any devices sold on Amazon or Walmart which would have the ability to stretch out the back and decompress the spine. This idea of just stretching out the back, or most specifically the lower back area, was one way which I believed would be effective in treating certain types of back pain as well as increase height. For years the idea of using something like a simple traction machine was promoted by many people in the community as effective.

Product Specifications

  • It is constructed of aircraft-grade aluminum making it lighter and easy to transport
  • It realigns your spine and improve your posture by stretching the entire skeleton from the shoulder blades to the ankles
  • Relieves back pain & increase the flexibility of the joints too.
  • Contoured foot supports secure the ankles into position
  • Commonly lengthens skeleton by 1 to 1-1/2 inches to increase flexibility
  • Folds to 20 x 11.5 x 3.5 inches (W x H x D)
  • Total weight: 5.5 pounds
  • You adjust it by pushing firmly with hands on the leverage handles
  • Entire kit includes a DVD instructional video with five 10-15 minute healthy back exercises.
  • Decompresses the discs to re-hydrate for better shock absorption and reduced back pain.

The P3 Portable Back Stretcher is Available From Here

Full Review

As a person who is now in my late 20s and almost 30, I have noticed certain types of muscle soreness in my lower back area. In fact, about 5 years ago when I was actively swimming a lot and stretching to gain height, I bought myself another type of product by Teeter Hang Ups, an inversion table, from the local Dick’s Sporting Goods Store. It was great since I had some success. Now, I wanted to look back at these devices, for both back pain relief and effectiveness in increasing height.

This product was the first one that we found. This product which is sold as the “Teeter Hang Ups P3 Portable Back Stretcher” is probably the first product which we found which blatantly states that it can increase the height of a person who uses the machine by a certain limit.

So does it make you taller from stretching out your bones?

The exact phrase that the sellers use in the product specifications states the following “Commonly lengthens skeleton by 1-1.5 Inches…”. If it works on the skeleton, it is stretching the person who plans to use it slightly past which is considered possible if they just did stretching of the back themselves. We’ve seen only a small handful cases of people who have managed to stretch themselves past even half an inch. The maximum I’ve heard of from any case was 3 cms, but that is only 1.25 Inches. This product is claiming to be able to do even more, upwards of 4 cms.

The problem is not that it doesn’t work, or that it give us what they promise. Based on what we’ve seen with rolfing, it is most likely work in giving at least 1 cm of increase in height if an adult uses it consistently for over 3 months.

What about back pain? Does it help treat back pain?

As for the back pain, it probably would have more success. However, with almost all traction devices, the pain it relieves could mean that it might cause a physiological change which would mean that the back can be adjusted so that the pain could be much worst if the problem is aggravated over again in a later time. We do believe that this product can treat back pain, but realigning the spine/vertebrate.

However, we have to be very careful on what type of pain we are trying to treat. There are some back pain where using a traction device would have no effect. Make sure that one understands that tensile loading the IVDs (intervertebral discs) would have a beneficial effect of pain relief and consult a medical specialist, or at least a chiropractor.

So whether you are trying to treat back pain through disc decompression or looking for other benefits, this type of portable back stretcher called the P3 from Teeter Hang Ups has a good chance that it would work.

So what do other people think of this back stretching device?

Check out what other people are saying about it here

Note: There are two purposes to start doing product reviews like this, one of which is to see how effective and viable are the devices in stretching out the skeleton to increase height, and the other is to get some extra income from the website. I plan to now start doing a reviews on maybe a few dozen back stretching and IVD decompression products I’ve found on Walmart, Amazon, and other Health Related major websites to get some extra affiliate income stream going.

Why Warren Grayson’s Research Will Be Revolutionary For Height Increasing Using Stem Cells For Tissue Reconstructive Engineering – Breakthrough!

Why Warren Grayson’s Research Will Be Revolutionary For Height Increasing Using Stem Cells For Tissue Reconstructive Engineering – Breakthrough!

For a long time me (and maybe Tyler also) have been keeping track of the research done by Robert Tracy Ballock and Cory Xian since the research they’ve been doing have been very close to what we are hoping to accomplish as well. I have read over Ballock’s work and he definitely has some brilliant insights, and since 2001 he even got an award for succeeding in growing a growth plate!

Tyler had found a grant that Ballock had done in the Cleveland Clinic “GROWTH PLATE REGENERATION” (Project #:1R21AR061265-01A1) at the US Department of Health and Human Services. Ballock has been working on both repairing growth plates that are damaged as well as growth epiphyseal cartilage in vitro which can in implanted into into damaged growth plate areas. However, I am not sure at this time if he has been doing research to grow a completely whole growth plate to be implanted into a bone which has no cartilage left to work with.

Xian has also been doing amazing work and the paper “POTENTIALS AND CHALLENGES OF GROWTH PLATE REGENERATION USING EX VIVO EXPANDED MESENCHYMAL STEM CELLS OR MOBOLISING ENDOGENOUS PROGENITOR CELLS” shows that he was trying to do the same thing as Ballock for the same types of application.

Of course, their goals have never been for cosmetic reasons but for medical reasons. The main goal has always been to help young children with active growth plates who have suffered injuries. In that particular paper, Xian revealed that for large animals, it seems that using MSCs taken from the marrow, and then using TGF-Beta1 to differentiate the MSCs into chondrocytes to form cartilage that can work with the injured epiphyseal plate was not successful.

As is written in the abstract… “To date, no large animal studies have reported successful regeneration of injured growth plate cartilage using MSC…” There are however at least two successes, one of which might have proven the study by XIan wrong

Case #1: In one of my biggest posts, I had shown that this researcher in Oregon named Alsberg had been able to use RGB injected into scaffolds to get a bone-cartilage tissue to grow volumetrically. His research group was the first back in 2002 to succeed in getting a growth plate to grow.

Case #2: Then there was Lee with his team back in 2002 who showed that adeno-virus mediated gene of the IGF-1 into an autologous muscle scaffold did have a favorable effect on repairing injured growth plates. (From the study entitled “Muscle-based gene therapy and tissue engineering for treatment of growth plate injuries“) My guess is that Xian was referring to large animals, and Lee was looking at much smaller lab animals. We here understand fully the difficulty in getting any type of explant to work properly.

Both of them are working on similar projects, but I feel that the person who probably is further along in the research than both of them is Warren Grayson who is currently at the John’s Hopkins University School of Medicine (Click Here to see his Lab’s Research) .

I looked at Grayson’s research and his Ph. D. Thesis entitled “Reconstructing the In Vivo Environment for the Development of Tissue-Engineered Constructs from Human Mesenchymal Stem Cells” (Available from Clicking Here) and noted that his work at Florida State University is when he was working for his Ph. D. Is almost exactly what I’ve been hoping to do this coming year.

From my personal research, it seems that the primary problem with trying to re-implant excised growth plates into a new bone defect/area is vascularization. When Thomas/Hakker did research on this issue a few years ago looking at surgeons trying to transfer growth plate cartilage into areas where bone bridges were resected into young kids which stunted growth due to bone bridges, he has found that all the studies he had found had said the results were not good. Again and again the problem seems to go towards vascularization.

From what we remember about the cartilage, unlike almost all other tissues, the cartilages in general have an environment which makes the cells inside them have great difficulty in getting the right types of nutrients. To get the necessary nutrients, the chondrocytes require that the nutrients diffuse through to the cells. This means that the nutrients don’t have a clear pathway to get to the cells. Most other cells have capillaries which run right by them which supplies them with the nutrients in the blood. We know that there is at least three major groups of blood vessels that go to the long bones. You have two groups of blood vessels which supplies to the epiphysis or the ends of the bone but you also have one large group of vessels reaching the middle of the long bones, the metaphysis. The general held belief on how the growth plates get their nutrients currently is that the blood vessels going into the ends of the bone contribute to the overall longitudinal growth. There was even a study which showed that if a surgeon took an awl and disrupted the blood vessels in that are going into the metaphysis, there was a noticeable increase in the longitudinal growth. And that is where the problem lies. If you are going to be trying to explant a piece of cartilage you grew in the lab, and implant it in the defect area to the growth plate cartilage that is still left, there is very little guarantee that the blood vessels will ever get to this new foreign area. If there is no vascularization, then the cartilage won’t survive. It will turn into bone matter, which forms a bony bridge.

This is where I feel Grayson’s research is most likely to work out. Grayson’s research is completely skipping over the idea of trying to push two cartilage pieces together to make them work and hope that the blood vessels start to seep into the new implant. It might just be smarter to try to build up one entire cartilage part, which will be implanted next to bone tissue instead. It was shown that back in 2007 Grayson was given a grant to build a tissue engineered model of the growth plate. Tissue Reconstructive Engineering

Notice the last phrase about him above….. There have been at least 3 papers he has published which shows that he is closer to a real solution that both Ballock and Xian since he has been creating a epiphyseal cartilage like scaffold which can be re-implanted back into the bone defects. They are….

I have personally downloaded all of the following studies above in PDF form and placed them in a private folder for me to later go through. There was however one study which I wasn’t able to get for free, which is “Engineering anatomically shaped vascularized bone grafts with hASCs and 3D-printed PCL scaffolds“.

I have emailed Dr. Grayson to ask whether he can give me a copy of this particular article.

Update 3/25/2014: After asking him politely and telling Dr Grayson of my intent to do tissue engineering research, he was kind enough to send me a copy of the PDF for free after just a short time. I want to thank him greatly for that gesture.

The one about how he is using a 3-D Printer to print out bio tissue, specifically cartilage is extremely promising. I will need to go over his 4 main articles to see whether he has succeeded or not. I am guessing that after the 6-7 years since he go the grant, he has managed to succeed in getting at least half there.

So what does this all mean for the average person hoping to increase height as an adult? 

Grayson’s research may find ways to grow large sized epiphyseal cartilage which would work as an implant. He might have been able to figure out how to get around the vascularization problem. It suggest that as early as just 15-20 years, there will be doctors who can in a clinical setting make adults increase in height using the tissue engineering method.

You can see a video of him explain the research he is doing below. I will also be doing a complete summary on his research in a future post.