| 摘要 |
An apparatus and method to modify the genetic regulation of mammalian tissue, bone, or any combination. The method may be comprised of the steps of tuning at least one predetermined profile associated with at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of predetermined tuned figures of merit is comprised of a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination to said at least one tuned time-varying stimulation field comprised of said at least one tuned predetermined profile for a predetermined tuned exposure time or plurality of tuned exposure time sequences. |
| 主权项 |
1. A method to modulate an increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family comprising the steps of:
tuning at least one predetermined profile of at least one time-varying stimulation field thereby resulting in at least one tuned time-varying stimulation field comprised of at least one tuned predetermined profile, wherein said step of tuning is comprised of,
providing at least one set of cellular samples in at least one rotating wall vessel;exposing said at least one set of cellular samples to at least one experimental time-varying stimulation field comprising at least one experimental predetermined profile;conducting at least one gene expression analyses of said at least one set of cellular samples;examining and determining an anabolic effect, catabolic effect, or no effect from the results of said at least one gene expression analyses;generating at least one conclusion from said step of examining and determining;comparing said at least one conclusion with predetermined criteria;if said at least one conclusion does not meet said predetermined criteria, adjusting said at least one experimental predetermined profile based on said at least one conclusion and repeating said steps of providing, exposing, conducting, examining and determining, generating, and comparing; andif said at least one conclusion does meet said predetermined criteria, selecting said at least one tuned time-varying stimulation field comprised of said at least one tuned predetermined profile for a predetermined tuned exposure time or a plurality of tuned exposure time sequences,wherein said at least one tuned predetermined profile is comprised of a plurality of tuned predetermined figures of merit and is controllable through manipulation of at least one of said plurality of tuned predetermined figures of merit, wherein said plurality of tuned predetermined figures of merit is comprised of two or more of the following: a tuned B-Field magnitude, tuned rising slew rate, tuned rise time, tuned falling slew rate, tuned fall time, tuned frequency, tuned wavelength, and tuned duty cycle;
controlling said at least one tuned predetermined profile comprised of manipulating said tuned B-Field magnitude to a first value between about 0.6 G to about 200 G and said tuned falling slew rate to a second value between about 2.0 kG/s and about 500.0 kG/s thereby resulting in a controlled at least one tuned time-varying stimulation field comprised of a controlled at least one tuned predetermined profile; and exposing mammalian chondrocytes, osteoblasts, osteocytes, osteoclasts, nucleus pulposus, associated tissue, or any combination thereof to said controlled at least one tuned time-varying stimulation field comprised of said controlled at least one tuned predetermined profile for said predetermined tuned exposure time or said plurality of tuned exposure time sequences thereby resulting in said increase, decrease, or both increase and decrease in the expression level of at least one gene or gene family selected from the group consisting of Wnt signaling family, WSP family, forkhead box (FOX) family, sex determining region Y (SRY) SOX family, parathyroid hormone (PTH) family, transforming growth factor (TGF) beta (TGF-β) super family, latent TGF family (ECM), integrin family (Cell Sulfur-Based (SUR): ECM), interleukin (IL) family (cellular cytokine response), thrombospodin family (COMPs), laminin family, proteoglycan family, osteoglycin, collagen family, insulin family, a disintegrin and metalloproteinase (ADAM) family, ADAM with thrombospondin motifs (ADAMTS) family, matrix metallopeptidase (MMP) family, actin family, catenin family, cadherin super family, B-cell lymphoma (BCL) family, calmodulin calcium-modulated gene, calumenin, cathepsin family, clusterin, cytochrome P 450 super family, endoglin, fibrillin family, fibroblast growth factor (FGF) family, leptin, MAP kinase activated protein kinases (MAPKAP) family, MSX homeobox family, NOTCH family, myotilin-myopalladin-palladin family, peroxisome proliferator-activated receptors (PPARA), Platelet Derived Growth Factor (PDGF) family, reticulocalbin, RUNX runt related transcription factors, signal transducer and activator of transcription (STAT) family, SMAD family, stanniocalcin family, SOD super oxide dismutase family, syndecan family, tumor necrosis factor (TNF) super family, AKT/PKB signaling family, and importin family. |
