Sunday, June 13, 2010

Becoming Taller with Mesenchymal Precursor Cells?

We know that increasing stem cell proliferation could lead to us becoming taller.  There are also precursor cells to stem cells and if we encourage them to differentiate into stem cells that could lead to a greater number of stem cells and thus again becoming taller.

G-CSF increases mesenchymal precursor cell numbers in the bone marrow via an indirect mechanism involving osteoclast-mediated bone resorption.

"During the course of studies to investigate whether MPC[Mesenchymal precursor cells] circulate in response to G-CSF[G-CSF is involved in causing the bone marrow to produce stem cells], the agent most frequently used to induce mobilization of hematopoietic progenitors, we observed that while G-CSF failed to increase the number of MPC in circulation (assayed in vitro as fibroblast colony-forming cells, CFU-F[CFU-F is the precursor cell to Mesenchymal Stem Cells]), G-CSF administration nevertheless resulted in a time-dependent increase in the absolute number of CFU-F within the BM, peaking at Day 7. Treatment of BM cells from G-CSF-treated mice with hydroxyurea did not alter CFU-F numbers, suggesting that the increase in their numbers in response to G-CSF administration is not due to proliferation of existing CFU-F. Given previous studies demonstrating that G-CSF potently induces bone turnover in mice, we hypothesized that the increase in CFU-F may be triggered by the bone resorption that occurs following G-CSF administration. In accord with this hypothesis, administration of an inhibitor of osteoclast differentiation, osteoprotegerin (OPG), prevented the increase of CFU-F numbers induced by G-CSF. In conclusion, these data indicate that the cytokine treatment routinely used to mobilize hematopoietic stem cells could provide a readily applicable method to induce in vivo expansion of MPC for clinical applications."

We know that osteoclasts are important in increasing height. According to this study, osteoclasts increase CFU-F(Mesenchymal Stem Cell precursors) thereby potentially increasing height.

Regulation of Mesenchymal Stem Cell Activity by Endothelial Cells.

"Emerging data suggest that mesenchymal stem cells (MSCs) are part of a periendothelial niche, suggesting the existence of heterotypic cell-cell cross-talk between endothelial cells and MSCs that regulate MSCs in their local microenvironment. We determined the effects of paracrine factors secreted by human umbilical vein endothelial cells (HUVEC) on MSC survival, proliferation and differentiation by using an optimised, serum-free HUVEC-conditioned medium (CM). HUVEC-CM induced a significant increase in the size and number of colony forming units-fibroblastic (CFU-F) and CFU-osteoblastic (CFU-O) and stimulated the proliferation of MSCs as determined by BrdU incorporation, compared to non-conditioned medium. We also demonstrated that CM significantly enhanced the osteogenic differentiation of MSCs as shown by alkaline phosphatase enzyme histochemistry and von Kossa staining of mineralised nodules as well as by qRT-PCR analysis of osteogenic markers. In contrast, there was no effect on the adipogenic differentiation of MSCs. Bioinformatic integration of HUVEC and MSC gene expression datasets identified several candidate signalling pathways responsible for mediating these effects including FGF, Wnt, BMP and Notch. These data suggest strongly that endothelial cells secrete a soluble factor (or factors) that stimulates progenitor cell activity and, selectively, the osteogenic differentiation of MSCs that could contribute to niche exit."

Endothelial cells line blood vessels and organs. Human Umbilicol Cords don't grow on trees.  Endothelial cell numbers are likely to increase in response to exercise however.

Large-scale extraction and characterisation of CD271(+) multipotential stromal cells (MSCs) from trabecular bone in health and osteoarthritis: Implications for bone regeneration strategies based on minimally-cultured MSCs.

"To test a hypothesis that CD45(low)CD271(+) bone marrow (BM) multipotential stromal cells (MSCs) are abundant in the trabecular bone niche and to explore their functional 'fitness' in health and osteoarthritis (OA). METHODS.: Following enzymatic extraction, MSC release was evaluated using colony-forming unit-fibroblast and osteoblast (CFU-F/CFU-O) assays, flow cytometry and confocal microscopy. FACS-isolated CD45(low)CD271(+) cells were enumerated and expanded in standard and clonal conditions. Their proliferative and osteogenic potencies were assessed in relation to donor age and compared to aspirated CD45(low)CD271(+) cells. In vitro and in vivo MSC 'ageing' was measured using qPCR-based telomere length analysis and standard differentiation assays were employed to demonstrate multipotentiality. RESULTS.: Cellular isolates from trabecular bone cavities contained approximately 65-fold more CD45(low)CD271(+) cells compared to aspirates (p<0.0001, medians 1.89%, n=39 and 0.029%, n=46, respectively), concordant with increased CFU-F release. Aspirated and enzymatically-released CD45(low)CD271(+) cells had identical MSC phenotypes ( approximately 100% CD73(+)CD105(+)CD13(+), approximately 50-60% CD146(+)CD106(+)CD166(+)) and contained large proportions of highly-clonogenic multipotential cells. In vitro osteogenic potency of freshly-isolated CD45(low)CD271(+) cells was comparable to early-passage MSCs (8-14%). Their frequency and in vivo telomere status in OA bone were similar to age-matched controls. CONCLUSIONS.: Our findings show that CD45(low)CD271(+) MSCs are abundant in the trabecular bone cavity and indistinguishable from aspirated CD45(low)CD271(+) MSCs. In OA they display ageing-related loss of proliferation but no gross osteogenic abnormality. These findings offer new opportunities for direct study of MSCs in musculoskeletal diseases without the requirement for culture-expansion. They are also relevant for direct therapeutic exploitation of prospectively-isolated, minimally-cultured MSCs in trauma and osteoarthritis."

The proliferative capacity of mesenchymal stem cells lowers with age.  There is an abundant amount of MSCs in the trabecular bone cavity(good news for LSJL) as shown by CFU-F numbers.

CFU-F is a precursor to Mesenchymal Stem Cells undergoing the chondrocyte lineage(which is what induces long bone growth).  Thus, it could result in us becoming taller through the usage of G-CSF, osteoclast released factors, and endotheliel cells.

According to Mobilization of endogenous stem cells: A new strategy for bone healing, AMD3100 and IGF-1 can increase stem cell mobilization.  "stromal cell-derived factor-1α (SDF-1α)/CXCR4" plays a role in stem cell migration.  AMD3100 disrupts the SDF/CXCR bond with anchors stem cells.  5mg/kg is the recommended dose of AMD3100.

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