Saturday, May 15, 2010

Grow Taller by increasing proliferation of mesenchymal stem cells?

The mesenchymal stem cells present in the red bone marrow in your epiphysis of your bones is a promising way of increasing height in your long bones.  It may be also possible to use MSCs to gain height in your short and irregular bones as after all they do draw bone marrow from your hip in bone marrow transplants.  The problem is of course that you may run out of Mesenchymal Stem Cells.  They are present in the body but there may not be enough of them.  To grow taller we want to maximize the amount of MSCs we have in our body.

Two ways of inducing stem cell proliferation are IGF-1 and Lithium.  IGF-1 is illegal and Lithium may be toxic to the kidneys(but in large quantities, even a small dose of Lithium should increase stem cell proliferation).  Of course load and strain has to have an impact:

[Response of bone marrow mesenchymal stem cells to mechanical stretch and gene expression of transforming growth factor-beta and insulin-like growth factor-II under mechanical strain]

"To study the response of rat bone marrow mesenchymal stem cells (MSCs) to a single period of mechanical strain and expression patterns of transforming growth factor-beta (TGF-beta) and insulin-like growth factor-II (IGF-II) after mechanical stretch. Bone marrow MSCs were isolated from SD rats and cultured in vitro. A four-point bending apparatus were used to perform a single period of mechanical strain (2000 microepsilon, 40 min) on MSCs. Cellular proliferation and alkaline phosphatase (ALP) activity of MSCs were examined and gene expression patterns of TGF-beta and IGF-II were detected by SYBR green quantitative real-time RT-PCR..  Cell proliferation, ALP activity and expression of TGF-beta and IGF-II were all significantly up-regulated in stretched MSCs when compared with their controls. The mRNA levels of TGF-beta and IGF-II got top increase immediately after mechanical loading and increased about 51.44 and 8.92 folds, respectively, when compared with control cells. Expression of TGF-beta and IGF-II decreased with time and returned to control level at 12 h after mechanical stimulus, despite of a small increase at 6 h. The mechanical stretch can promote MSCs proliferation, up-regulate its ALP activity and induce a time-dependent expression increase of TGF-beta and IGF-II which in turn result in osteogenic differentiation of MSCs. Mechanical stimulus is a key stimulator for osteogenic differentiation of MSCs and vital for bone formation in distraction osteogenesis."

Of course, how do we actually physically stretch the mesenchymal stem cells?  The MSCs are in the bone marrow which are in the trabecular bone in the epiphysis.  Although, a compression force like lateral synovial joint loading puts a mechanical strain on the trabecular bone which should in turn put a strain on the mesenchymal stem cells within the bone marrow.  The preference for MSCs to osteogenically differentiate shouldn't matter except in as mentioned in the study in distraction osteogenesis where new bone needs to be formed in the gap.  You definitely would not want your MSCs to differentiate into fat cells!  In the hyaline cartilage growth plate line you want them to differentiate into chondrocytes.

 Autocrine BMP4 signaling involves effect of cholesterol myristate on proliferation of mesenchymal stem cells.

 "Cholesterol myristate in traditional Chinese medicine (TCM) is the active compound that increases proliferation of mesenchymal stem cell (MSCs).  Reverse transcription-PCR, Western blot and ELISA analysis show that cholesterol myristate increases the release of bone morphogenetic protein 4 (BMP4) from MSCs and the expression in the intracellular levels of BMP4 in a time- and dose dependent manner. However, structurally related steroids such as cholesterol and cholesten presented in TCM, both lack of the myristate, did not affect the secretion and expression of BMP4 on MSCs. These finds suggest that myristate is essential for the effects of cholesterol myristate. Furthermore, cholesterol myristate significantly increase BMPRIB levels of MSCs and the number of BMPRIB positive cells in a time- and dose dependent manner, but not BMPR IA or BMPR II. Our results indicate that action of cholesterol myristate may activate the BMP4-BMPRIB autocrine. Moreover, a blocking antibody against BMP4 or the BMP4 antagonist, noggin, partially reduced the effects of cholesterol myristate on MSCs proliferation. Autocrine BMP4 signaling involves effect of cholesterol myristate on MSCs proliferation."

Unfortunately, I could only find cholesterol myristate available in China.  Bone morphogenic protein-2 also increases proliferation of mesenchymal stem cells but that's not really something you can buy in the store.  Connective tissue growth factor could also enhance proliferation of mesenchymal stem cells and it's possible that by dynamic compressive loading of the connective tissue LSJL could enhance expression of this growth factor.  Low Magnitude Mechanical Signals also increased bone marrow stem cells but I'm not sure what that is(Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity).

 This basically confirms the things we already know like exercise and LSJL are good.  We also need to find a way to bring Cholesterol Myristate to other locations besides China.  

Mesenchymal Stem Cell Mechanobiology

"intracellular tensile forces resulting from cell–extracellular matrix interactions play a critical role in MSC regulation"

This diagram shows that the scientists believe that mechanical strain and/or fluid flow can induce differentiation of MSCs into chondrocytes.

"Genes involved in regulating MSC “stemness” include Thy-1 glycan, decorin, dickkopf-2, thrombospondin 1, steroid-sensitive gene-1, and CD73"

"The cytoskeleton is naturally in a state of tension, a concept known as “tensegrity,” and these tensile forces act through focal adhesions and pull on the underlying basement membrane resulting in degradation of the extracellular matrix (ECM). ECM degradation causes cell spreading and development of tensile forces, which in turn initiates proliferation and localized tissue expansion resulting in tissue folding."

" intracellular tensile forces resulting from cell–ECM interactions are potent enough to induce differentiation and small forces may be just as critical as larger external forces in directing stem cell fate."<-so forces like from that such as LSJL may be enough to induce differentiation.

"oscillatory fluid flow enhanced expression of Runx2, Sox9, and peroxisome proliferator-activated receptor-γ, and activated RhoA in the murine multipotent C3H10T1/2 cell line. "

Although "Human MSCs subjected to FSS[fluid shear stress] exhibit increased expression of collagen 1a1, osteopontin, osteocalcin, bone sialoprotein, BMP-2, BMP-4, and BMP-7, transforming growth factor-β1, VEGF-A, and ALP. "

"Expression of Wnt5a and Ror2, both of which activate RhoA, was enhanced in response to FSS"

"[Continuous uniaxial cyclic strain on rat MSCs] of 7.5% or greater led to apoptosis through activation of L-type voltage-activated calcium channels and downstream c-Jun N-terminal kinase signaling."

Both Fluid Shear Stress and Cyclic Tensile Strain have been shown to induce MSC proliferation.

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