As post-WWII baby boomer approaching age 80, Anti-Aging Regenerative Cosmetology (AARC) has been developed and patented for beautifying and strengthening the human body using live cells; to enhance the appearance and function of various bodily parts to provide health and aestheticism of human being throughout life. It is a combined cosmetic and preventive medicine to intervene with and to correct the undesirable phenotypic expression of aging. The intrinsic properties of myoblasts and foreskin fibroblasts in development and regeneration are harnessed to formulate a genetic cell therapy program which is safe and efficacious as previously been tested in FDA Phase III clinical trials. Myoblasts are selected for strength development and foreskin fibroblasts for tenacity and smooth-to-the-touch. Both cell types are highly mitotic and non-carcinogenic. In additional to providing large quantities of nuclei as regenerative gene medicine, and of mitochondria as energy generators, myoblasts secret tumor necrosis factor alpha (TNF-α) for skin whitening and melanoma prevention. Myoblasts, because of their small size, spindle shape, and resilience, grow readily on collagen and laminin within wrinkles of skin surfaces, thus enhancing the color, luster, and texture of the skin “plated” with them. Alternatively, they can be injected subcutaneously as cell filler to reduce wrinkles. Intramuscular injection of myoblasts can augment the size, shape, consistency, tone, and strength of muscle groups, improving the lines, contours, and vitality to sculpt a youthful appearance. By improving cell genetics and organ functions, the program holds promise to sustain the human subject in good health and appearance, with a good quality of life and life prolongation.

This article reviews the scientific and intellectual property development of a biotechnology platform in regenerative medicine called Human Myoblast Genome Therapy (HMGT), known previously as Myoblast Transfer Therapy (MTT). Myoblasts are the least differentiated myogenic cells capable of extensive division, natural cell fusion, nucleus transfer, cell therapy and genome therapy. Myoblasts cultured from muscle biopsy survive, develop and function, after transplantation in animal studies and clinical trials, to revitalize degenerative organs in heart failure, ischemic cardiomyopathy, Type II diabetes, muscular dystrophies, aging dysfunction and disfigurement. Myoblasts have also been used to enhance skin and muscle appearance in cosmetology. HMGT replenishes live cells and genetically repairs degenerating myofibers. It is the worlds first human gene therapy when it replenished dystrophin in Duchenne muscular dystrophy as reported in Lancet on July 14, 1990. Data from FDA- approved Phase II/III muscular dystrophy clinical trials demonstrated significant safety and efficacy to merit allowance of cost recovery in consecutive years. Data from FDA- and EMA- approved Phase II/III ischemic cardiomyopathy clinical trials demonstrated significant safety and efficacy. This review also provides in-depth analyses of key factors related to success and failure of HMGT procedures. Future development will focus on myoblasts transduced with VEGF165 using nanoparticles or liposomes that are promising biologics for angiomyogenesis. Automated cell processors, myogenic cell injection catheters and methods of use have been patented to complement the HMGT technology. Keywords: Myoblasts, biologics, muscular dystrophies, heart failure, ischemic cardiomyopathy, Type II diabetes, anti-aging cosmetics, automated cell processors, catheters, Human Myoblast Genome Therapy (HMGT), Myoblast Transfer Therapy (MTT), transplantation techniques, myogenic cells, biopsy, Duchenne muscular dystrophy (DMD), hereditary degenerative diseases, replenish live cells, Cell fusion, Genome therapy, multi-nucleated heterokaryon, vascular endothelial growth factor (VEGF165), Allograft immunogenicity, current good manufacture practices (cGMP), standard operation procedures (SOP's), Drug Master File (DMF), mycoplasmal contamination, penicillin, myoblast injection techniques, SKELETAL MUSCLE REGENERATION, dystrophic satellite cells, Mesenchymal tissue, cyclosporine-A, dystrophin, immunocytochemical localization, horseradish peroxidase (HRP), immunocytochemistry, Dulbecco's Modified Eagles Medium (DMEM), phosphatebuffered saline (PBS), sarcolemma, gel electrophoresis, Histoincompatible Transplants, Cyclosporine, Histocompatible Transplants, muscle twitch tension, tetanus tension, mechanophysiology, supramaximal nerve stimulation, Sporadic flexion, flaccid extension, hybrid isozymes, European Patent Agency (EPA), Myoblast Therapy for Mammalian Diseases, somatic cell therapies, gene therapies, double-blind study, phagocytic necrosis, sham-injected muscles, first human gene therapy, lower body treatment (LBT), ankle plantar flexors, knee flexors, knee extensors, ambulatory subjects, degenerated proximal muscles, myogenicity, neuromuscular junctions, T-lymphocyte proliferation, whole body treatment (WBT), infantile facioscapulohumeral dystrophy, isometric force, creatine kinase (CK), aspartate aminotransferase, Duchenne Muscular Dystrophy, HEART MUSCLE DEGENERATION, congestive heart failure, endomyocardial injections, electrocardiogram, Transmyocardial perforation, Myostar catheter, regenerative heart, Single-Photon Emission Computed Tomography, multinucleated heterokaryons, xenografts, reverse transcription polymerase chain reaction, angiogenesis, Polyethylenimine-25 nanoparticles, coronary artery bypass grafting (CABG), atherosclerosis, Echocardiography, fibroblast infiltration, ANTI-AGING AESTHETICA (AAA), Regenerative Medicine, Cell transplantation, Angiomyogenesis, cytogenetics

Objectives: Allogeneic myoblast transplantation (AMT), cyclosporine immunosuppression and coronary artery bypass grafting (CABG) were used to treat end-stage heart failure (HF) subjects without hope of obtaining a heart transplant. Background: Severe myocardial infarction conveys serious complications such as ventricular aneurysm, wall thinning and rupture with fatal consequences. Methods: After meeting Inclusion/Exclusion criteria and signing Patient Informed Consents, 10 HF subjects having mean thinnest wall thickness of 2.21 ± 0.55 mm and ventricular aneurysms were admitted under intensive care. Each subject took daily cyclosporine for three weeks. On the third day of cyclosporine administration, approximately 1 billion myoblasts were implanted through 20 injections into the infarcted myocardium following CABG. Results: Safety No subject suffered death, viral infection, malignant arrhythmia, reduction in cardiac output, immune rejection, or aneurysm growth. No significant difference was found before versus after treatment in the mean levels of blood routine, liver and kidney enzymes, electrolytes and fibrinogen. Efficacy Emission computed tomography (ECT) and magnetic resonance (MR) demonstrated significant increases in viability and perfusion. Mean left ventricular ejection fraction (LVEF) significantly increased (P Conclusions: For the first time, AMT in adjunct use with CABG and cyclosporine demonstrated that cell survived and engrafted in patients with ischemic cardiomyopathy; in this small study the cell transplant was safe. The improvement in heart function and quality of life could be secondary to combined effect of bypass and cell transplant. A larger randomized clinical trial is required to confirm the efficacy.

Life-saving procedures of an emergency protocol to combat fatal ambushes of viral or bacterial pathogens are listed below for immediate dissemination and implementation. This unique protocol of serum therapy commands the highest benefits-versus-risks ratio, and is safe, efficacious, user-friendly and inexpensive to implement. A formal evaluation is presented to support upgrading convalescent plasma therapy to serum therapy in the context of presenting fewer donor antigens, thus evoking less lethal sensitization to obtain greater safety and efficacy in treatment.

This is a succinct and current review of pertinent literature to guide developing serum therapy as an emergent treatment to save human lives at times of natural or genetically engineered viral/bacterial pandemics. The origin of 2019-nCoV and implications of COVID-19 are discussed using direct quotes of published scientific literature to avoid misinterpretation on this very important event that has caused great loss of human lives and international social economy. It is the goal of this review to warn against and to correct international misunderstanding created by deliberate falsification of scientific documentations and events. This misunderstanding may lead to further destruction of life, economy, and political relations. People should not be blind-sighted when making life decisions.

The science behind two life-saving protocols to combat COVID-19 and future pathogenic epidemics is presented for immediate implementation.

In the 500 million years of vertebrate evolution, the skeletal muscle, being externally located in the body, has developed specific characteristics for frontline defense against predation, including diseases. Myoblast implantation is a unique, patented technology of muscle regeneration having been tested in phase III clinical trials of muscular dystrophy and ischemic cardiomyopathy, phase II trial of cancer, and phase I trial of type 2 diabetes. Differentiated and committed, myoblasts are not stem cells. They fuse spontaneously and develop to form "new" myofibers, replenishing skeletal myofibers in muscular dystrophy. They develop to become cardiomyocytes in the infracted myocardium. They also fuse with degenerative myofibers of muscular dystrophy or type 2 diabetes, transferring their nuclei containing the normal human genome to provide stable, long-term expression of the missing gene products. When billions of myoblasts are injected into a solid tumor, membrane breakage prior to cell fusion releases high concentration of tumor necrosis factor-a to inhibit cancer growth and metastasis by inducing apoptosis and cell cycle arrest of cancer cells. Newly formed myotubes use up most of the nutrients and oxygen within the tumor and starve the cancer cells. They wrap around cancer cells and prevent them from metastasis. Furthermore, myoblast allograft generates antibodies and triggers localized immune attack on the cancer cells nearby. Myoblasts, because of their small size, spindle shape, and resilience, grow readily within wrinkles and on skin surfaces, thus enhancing the color, luster, and texture of the skin "plated" with them. They can be injected subcutaneously as a cellular filler to reduce wrinkles. Intramuscular injection of myoblasts can augment the size, shape, consistency, tone, and strength of muscle groups, improving the lines, contours, and vitality from the sculpture for a youthful appearance. This highly promising technology has great social economic values in treating hereditary, fatal, and debilitating disease conditions.

Evolution of placental mammals over the past 160 million years witnesses the relative sparing of muscles from cancer attacks. In 1) nude mice with human gastrointestinal or lung tumors, and 2) human subjects with liver, lung or gastrointestinal tumors, intra-tumor implantation of allogeneic human myoblasts induced cancer apoptosis, inhibiting metastasis and tumor growth. We postulate four mechanisms of cancer apoptosis: a) myoblasts releasing tumor necrosis factor-α (TNF-α); b) deprivation of nutrients and oxygen; c) local inflammatory and immunologic attacks; and d) prevention from metastasis. These basic and clinical studies demonstrated preliminary safety and efficacy of intra-tumor myoblast implantation in the development of prevention and treatment for cancer, now the number one disease killer of mankind.

This article discusses existing catheter systems and proposes a conceptual design and procedure for an autonomous cell injection catheter for the purpose of transferring committed myogenic or undifferentiated stem cells into the infarct boundary zones of the left ventricle. Operation of existing catheters used for cell delivery is far from optimal. Commercial injection catheters available are handheld devices operated manually by means of tip deflection and torque capabilities. Interventionists require a hefty learning curve and often encounter difficulties in catheter stabilization and infarct detection, resulting in lengthy operation times and nonprecise injections. We examined current technologies and proposed a design incorporating robotic positional control, feedback signals, and an adaptable operational sequence to overcome these problems. The design provides the basis for robotic catheter construction that is able to autonomously assist the physician in transferring myogenic cells to the left ventricle infarct boundary zones.

Remote and robotically actuated catheters are the stepping-stones toward autonomous catheters, where complex intravascular procedures may be performed with minimal intervention from a physician. This article proposes a concept for the positional, feedforward control of a robotically actuated cell injection catheter used for the injection of myogenic or undifferentiated stem cells into the myocardial infarct boundary zones of the left ventricle. The prototype for the catheter system was built upon a needle-based catheter with a single degree of deflection, a 3-D printed handle combined with actuators, and the Arduino microcontroller platform. A bench setup was used to mimic a left ventricle catheter procedure starting from the femoral artery. Using Matlab and the open-source video modeling tool Tracker, the planar coordinates ( y, z) of the catheter position were analyzed, and a feedforward control system was developed based on empirical models. Using the Student's t test with a sample size of 26, it was determined that for both the y- and z-axes, the mean discrepancy between the calibrated and theoretical coordinate values had no significant difference compared to the hypothetical value of µ = 0. The root mean square error of the calibrated coordinates also showed an 88% improvement in the z-axis and 31% improvement in the y-axis compared to the unmodified trial run. This proof of concept investigation leads to the possibility of further developing a feedfoward control system in vivo using catheters with omnidirectional deflection. Feedforward positional control allows for more flexibility in the design of an automated catheter system where problems such as systemic time delay may be a hindrance in instances requiring an immediate reaction.

The world needs to know the facts as to how the FDA "protects" the public health by assuring the safety, effectiveness, and security of human drugs and biological products for human use.Recent uproar has surfaced over the FDA's approval process on the unproven Duchenne Muscular Dystrophy (DMD) drug, Exondys 51 (Sarepta Therapeutics, Cambridge, MA, USA), but what many people do not know are the unlawful events that occurred nearly two decades ago on a proven and promising treatment for DMD.

Myoblast implantation is a unique, patented technology of muscle regeneration being tested in Phase III clinical trials of muscular dystrophy, ischemic cardiomyopathy, Phase II trial of cancer, and Phase I trial of Type II diabetes. Differentiated and committed, myoblasts are not stem cells. Implanted myoblasts fuse spontaneously among themselves, replenishing genetically normal myofibers. They also fuse with genetically abnormal myofibers of muscular dystrophy, cardiomyopathy, or Type II diabetes, transferring their nuclei containing the normal human genome to provide stable, long-term expression of the missing gene products. They develop to become cardiomyocytes in the infracted myocardium. Myoblasts transduced with VEGF165 allow concomitant regeneration of blood capillaries and myofibers. They are potent biologics for treating heart failure, ischemic cardiomyopathy, diabetic ischemia, erectile dysfunction, and baldness. Myoblasts, because of their small size, spindle shape, and resilience, can grow within wrinkles and on skin surfaces, thus enhancing the color, luster and texture of the skin “plated” with them. They can be injected subcutaneously as a cellular filler to reduce wrinkles. Intramuscular injection of myoblasts can augment the size, shape, consistency, tone and strength of muscle groups, improving the lines, contours and vitality to sculpt a youthful appearance. This highly promising technology has great social economic values in treating hereditary, fatal and debilitating disease conditions.

This paper provides an overview of the conventional therapeutic stimulation methodologies and proposes a more effective stimulation approach based on a consideration of the inherently fractal nature of normal biological dynamics. There are varying forms of physiological stimulations including the use of electrical currents, electromagnetic fields, temperature change, ultrasound, light and so forth. These stimulation therapies can be categorized into three main modalities: electrical stimulation modalities, thermal modalities, and non-thermal modalities. Electrical stimulation modalities include therapeutic techniques where electrical current is directly applied to the body of treated subject. Direct application of electrical current to the brain also falls under this category. Thermal modalities consist of stimulations that induce temperature change on the body for therapeutic effects without the direct transfer of electrical current. Non-thermal modalities functions through energy transfer without directly applying electrical current and without the effects of temperature change. A fourth miscellaneous category for stimulation techniques consists of the stimulation effects of music along with physical stimulation as in massage therapy. Common to most of these therapeutic strategies is that the stimulation is delivered at certain fixed periods or frequencies. We introduce some rudiments of fractal dynamics, and the notions of self-similarity, scale-invariance, and long-range correlation or memory in the dynamics of a system. We present evidence that fractal dynamics is commonly observed in healthy physiological systems while unhealthy systems are shown to veer away from fractal dynamics towards periodic or random motion. This difference in dynamics can be observed in many biological signals such as in neural activity, heart rate variations, and breathing patterns. We propose that an optimal stimulation technique should thus be one that encourages an unhealthy, non-fractal pathological system towards a healthy, fractal dynamic. Given the ubiquity of fractality in healthy biological dynamics, we argue that a fractal pattern of stimulation is a more optimal approach to functional restoration than the widely used conventional periodic stimulation, which may further consolidate the existing pathological dynamics.

Aim: The study aims to investigate the gene expression profiling of insulin signaling pathway and mitochondrial biogenesis and function in the skeletal muscle of KK mice.Methods: KK mice were divided into the following groups: KK control group, basal medium (M199) only; KK fibroblast group, with human fibroblast transplantation; KK myoblast group, with human skeletal myoblast transplantation. C57BL mice received hSkM transplantation as a normal control. Cells were transplanted into mice hind limb skeletal muscle. All animals were treated with cyclosporine for 6 weeks only. The mice were sacrificed in a fasting state at 12 weeks after treatment. Hind limb skeletal muscle was harvested and used for study of gene expression profiling.Results: hSkMs survived extensively in mice skeletal muscle at 12 weeks after cell transplantation. Glucose tolerance test showed a significant decrease of blood glucose in the mice of KK myoblast group compared to the KK control and fibroblast groups. Transcriptional patterns of insulin signaling pathway showed alterations in KK myoblast as compared with KK control group (23 genes), KK fibroblast group (7 genes), and C57BL group (8 genes). Transcriptional patterns of mitochondrial biogenesis and function also had alterations in KK myoblast as compared with KK control group (27 genes), KK fibroblast group (9 genes), and C57BL group (6 genes).Conclusions: These data demonstrated for the first time that hSKM transplantation resulted in a change of gene transcript in multiple genes involved in insulin signaling pathway and mitochondrial biogenesis and function. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

Massive cell death associated with poor donor cell survival was a limiting factor in the success of myoblast transfer therapy (MTT). The current study is aimed to determine the effects of thymosin & β 4 on human skeletal myoblast (hSkM) migration, proliferation and survival under hypoxia. hSkM was cultured in basal medium (BM, M199 medium with 10% fetal bovine serum) supplemented with various concentrations of thymosin & β 4. Supernatant was collected to test the toxicity of thymosin & β 4 towards hSkM. Cell number was quantified using CyQuant cell proliferation assay kit. Cell viability was determined by calculating the lactate dehydrogenase (LDH) in the supernatant. hSkM migration was determined using cell culture insert. No significant toxicity of thymosin & β 4 towards hSkM was found when thymosin & β 4 was increased up to 600ng/ml. Thymosin & β increased hSkM proliferation rate by 35.4+13.4% at 600ng/ml. It enhanced hSkM viability (cell injury =10.9±1.7%) as compared with control (cell injury = 24.6%, p < 0.05) under hypoxia (5% CO2+ 94% N2+1% O2) for 48 hours (hrs). Increased migration rate (164.5+15/well, p < 0.05 vs control) was achieved with thymosin & β 4 at 100ng/ml concentration. Thymosin & β 4 increased the activities of PI3K and AKT, and reduced the activities of caspases 3 and 8. We conclude that thymosin & β 4 increased hSkM migration and proliferation. It enhanced hSkM viability under hypoxia, providing a new strategy to improve hSkM survival in MTT. Furthermore, recent patents on thymosin & β 4 and skeletal myoblasts as therapeutic agents will be discussed. Keywords: Cell viability, migration, proliferation, skeletal myoblasts

This article reviews the scientific development of angiomyogenesis using VEGF165-myoblasts, a patented biotechnology platform in regenerative medicine associated with Human Myoblast Genome Therapy (HMGT), also known as Myoblast Transfer Therapy (MTT). VEGF165-myoblasts are the leading biologics for angiomyogenesis. This review also compares the safety and efficacy of VEGF165-myoblasts transduced using adenoviral vectors, nanoparticles or liposomes, in anticipation of their application in clinical trials in the near future. VEGF165-myoblasts are differentiated myogenic cells capable of extensive division, natural cell fusion, nucleus transfer, cell therapy and genome therapy. Following transplantation they survive, develop and function to revitalize degenerative myocardium in heart failure and ischemic cardiomyopathy animal studies. VEGF165-myoblasts are second generation products of HMGT/MTT which replenishes live cells and genetically repairs degenerating myofibers in Type II diabetes, muscular dystrophies, aging dysfunction and disfigurement. Myoblasts have also been used to enhance skin and muscle appearance in cosmetology. We envision that VEGF165-myoblasts will provide better outcome than their non-tranduced counterparts. Myoblasts are not stem cells. Their competitive advantages over stem cells are presented.

Aims/hypothesis We aimed to demonstrate the feasibility and efficacy of intra-muscular transplantation of human skeletal myoblasts (hSkMs) for attenuation of hyperglycaemia and improvement of insulin sensitivity using a mouse model of type 2 diabetes mellitus. Methods KK Cg-Ay/J mice, aged 12 to 14 weeks, underwent an initial intraperitoneal glucose tolerance test (GTT) and were divided into the following groups: KK control group, basal medium (M199) only; KK myoblast group, with hSkM transplantation; KK fibroblast group, with human fibroblast transplantation. Non-diabetic C57BL mice were used as an additional normal control and also had hSkM transplantation. Cells were transplanted intra-muscularly into the skeletal muscles of the mice. All animals were treated with ciclosporin for 6 weeks only. HbA 1c and fasting GTT, as well as serum adiponectin, cholesterol, insulin and triacylglycerol were studied. Results Immunohistochemistry studies showed extensive survival of the transplanted hSkMs in the skeletal muscles at 12 weeks, with nuclei of the hSkMs integrated into the host muscle fibres. Repeat GTT showed a significant decrease in glucose concentrations in the KK myoblast group compared with the KK control and KK fibroblast groups. The KK myoblast group also had reduced mean HbA 1c , cholesterol, insulin and triacylglycerol, and increased adiponectin compared with the KK control and KK fibroblast groups. C57BL mice showed no change in glucose homeostasis after hSkM transplant. Conclusions/interpretation Human skeletal myoblast transplantation attenuated hyperglycaemia and hyperinsulinaemia and improved glucose tolerance in the KK mouse. This novel approach of improving muscle insulin resistance may be a potential alternative treatment for type 2 diabetes mellitus.

Human Myoblast Gcnomc Thcrapy(HMGT)is a p1atfom tcchnology of ccll transplantation,nudcar transfcr,and tissue engi11ccring Un1i1ζe stem cells,myoblasts are dlfferentiated,immamrc celk dcsti11cd to become muscles,Myoblasts culmred iom satc11itc cclls of adu11. musde bops始 s survive,develop,and nInct。 nt。 rcvital讫 e dcgcncrativc musdes upon transplantation I刂 ection 硒 ury activates regencration ofhost myoII bcrs that血se with thc cngraRed myoblasts,sh舶 ng their nuclei in a∞ mnon gene poolof伍 e syncytlum Thus,through nuClear transfcr and complementaton,the norlnal human gcnome can be transfeII ed into muscles ofpat始 nts with gcnetic disordcrs to achicvc phcnotypc rcpair or discasc prcvcntion.Myoblasts arc safc and cfflcicnt gcnc transfcr Vchiclcs endogenous to musdcs that constitutc50%ofbody wcight Rcsults ofovcr280HMGT proccdurcs on Duchcnnc Muscular Dystrophy (DMD)su历 ccts in thc past15years demonstratcd abso1ute safety Myob1ast-i犭 edCd DMD musdes showed improved histology, strcngth increase at18months post-opcrativc1y avcragcd123% In anothcr apphcation of HMGT on ischen1ic cardiomyopathy,thc flrst human myob1ast transfer into porcine myocardium revealed that it、 vas safc and cffective Clinical trials on approximately220 scvcre Cardiomyopathy patients in15∞ untries showed a(10%mortaliy Most su旬 ccts received autologous cells implantcd on伍 c epicardial surfacc during coronory artery bypass graa,or i犭 cctCd on thc endomyocardial surfacc pcrcutancOusly through guiding cathctcrs signiflcant incrcascs in lcR vcntr16. ular苟 Cctlon fraCtlon,wall伍 忆kncss,and wa11mot16.n havc bccn rcportcd,wi伍 rcducton in pcrfusion defective areas,angina,and shortness of brcath As a ncw modahty oftreatmcnt for discasc in thc skclctal muscle or myocardium,IIMGT cmcrgcd as safe and cffcctivc.Largc randomizcd multi-center trials arc undcr、 Vay to conflm these preII minary results,The血 turc ofHMGT is bright and cxciting('Cε F洳rr CJ′′%′′@J2006;3:135-51讠