Me: I found these three studies which gave me another idea on how to possibly lengthen the long bones. The issue with this proposed method is that even in theory, there is only a small chance that it can increase the long bone’s length and only by a little, if the gene therapy is the only thing used. If we can combine the gene therapy method involved with a form of mechanical loading or invasive surgical distraction, the chances of achieving long bone lengthening will be increased dramatically.

Description & Analysis: What we see here is that genetically engineered pluripotent human mesenchymal stem cells can be grown and implanted with certain types of vectors which mutates them completely and causes them to overexpress on certain types of genes. In the first study, the already rhBMP-2 cells are injected even further with a new type of compound I am not familiar with, a lacZ gene, that encodes for beta-galactosidase. The researchers conclude very clearly that “the ability of GEPMC to engraft, differentiate, and stimulate bone growth“. If the GEPMCs can be mutated in vitro to have certain types of characteristics, why can we not just use gene therapy to cause the cells to overexpress chondrogenetic growth factors? In the 2nd study, we see that the vector used was to encapsulate BMP-2. After that the researchers injected doxycycline to control the growth of  bone. This means that after we get the first injection of MSCs in, that does not mean that we can do nothing to control the chondrogenesis anymore. Using doxycycline, we can cause the cells to probably be even more effective in the gene expression. The 3rd study state conclusively that “they can be genetically engineered to express desired therapeutic proteins inducing specific differentiation pathways.”

Actual Method: The method is still invasive because it has to penetrate tissue and bone. Let’s assume the idea of LSJL is valid. That means that as long as we can get cell differentiation towards chondrogenesis, proliferation, and hypertrophy, then the bones can lengthen. I then proposed that we first use gene therapy to mutate at least 2 batches of a certain type of MSCs. We first extract the MSCs of the patient from their long bone to get the re-implant to be immunologically compatible. We then add one type of vector for each of the two groups. For the first batch of mutated MSCs, we use vectors to get to cause them to focus on only expressing chondrogenesis genes. Once we accomplish that, we inject this first group of cells into the epiphysis ends of the long bones through drilling. After the cells are added, we can wait for 1-4 weeks. After we are sure the differentiation is complete, we want to expand the number of chondrocytes inside. That is when we get the 2nd group of MSCS to focus on overexpressing the genes that produce the growth factors that lead to chondrocyte proliferation. This in theory should not only cause the already chondrocytes implanted to multiply, it should also get the original MCSs in the epiphysis to differentiate as wel and join with the implanted groupl. Sure, we could make the argument that only the 2nd group of implants are needed, but from what I have learned about crystal growing ,it is always  better idea to start with a seed, and have it grow bigger and bigger but getting the surrounding medium and raw material to transform into it and then layer on top of it. Once this is done, there will be a substantial amount of chondrocytes in the human epiphysis. Since LSJL theory says induced chondrogenesis proliferation will lead to bone lengthening, then this proposed method should lengthen the bone. We then can use compounds like doxycyline, to control the rate of bone growth. To help the bone growth further along by causing chondrocyte aggregation, we can then apply ESW therapy in that area to help the Chondrocytes already there to lead to hypertrophy and expand.

From PubMed study 1 link HERE…

J Gene Med. 1999 Mar-Apr;1(2):121-33.

Engineered pluripotent mesenchymal cells integrate and differentiate in regenerating bone: a novel cell-mediated gene therapy.