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.

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….

• Engineering cartilage and bone using human mesenchymal stem cells
• Engineering custom-designed osteochondral tissue grafts
• Tissue Engineered Bone Grafts: Biological Requirements, Tissue Culture and Clinical Relevance

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.