CAM and cell fate targeting: molecular and energetic insights into cell growth and differentiation

Abstract

Evidence-based medicine is switching from the analysis of single diseases at a time toward an integrated assessment of a diseased person. Complementary and alternative medicine (CAM) offers multiple holistic approaches, including osteopathy, homeopathy, chiropractic, acupuncture, herbal and energy medicine and meditation, all potentially impacting on major human diseases. It is now becoming evident that acupuncture can modify the expression of different endorphin genes and the expression of genes encoding for crucial transcription factors in cellular homeostasis. Extremely low frequency magnetic fields have been found to prime the commitment to a myocardial lineage in mouse embryonic stem cells, suggesting that magnetic energy may direct stem cell differentiation into specific cellular phenotypes without the aid of gene transfer technologies. This finding may pave the way to novel approaches in tissue engineering and regeneration. Different ginseng extracts have been shown to modulate growth and differentiation in pluripotent cells and to exert wound-healing and antitumor effects through opposing activities on the vascular system, prompting the hypothesis that ancient compounds may be the target for new logics in cell therapy. These observations and the subtle entanglement among different CAM systems suggest that CAM modalities may deeply affect both the signaling and transcriptional level of cellular homeostasis. Such a perception holds promises for a new era in CAM, prompting reproducible documentation of biological responses to CAM-related strategies and compounds. To this end, functional genomics and proteomics and the comprehension of the cell signaling networks may substantially contribute to the development of a molecular evidence-based CAM.

Figure 1

Putative signaling networks encompassed by CAM strategies. Increasing evidence indicates that acupuncture leads to the expression ofc-fos and c-jun genes and their related protein products, which act as growth regulatory transcription factors. Concerted activation of Fos/Jun expression by electroacupuncture has emerged as a molecular mechanism underlying the increase in the expression of targeted endorphin genes. Additionally, old nutraceuticals commonly used in Chinese traditional medicine have been found to have the potential for differentiating logics, acting on cell renewal and lineage commitment in pluripotent cells. Exposure to magnetic energy may ultimately result in the activation of signaling network(s) previously believed to be activated solely in the presence of a growth factor. Future directions may involve the analysis of CAM-related approaches within the context of the molecular examination of a number of signal-transduction mechanisms, including the activation of selected G-protein coupled receptors and the interplay between the subcellular redistribution patterning of defined kinaseisozymes and the activation of tissue-restricted transcription factors (a representative scheme of a tyrosine receptor kinase signaling is shown). The analysis of long-lived signals, involving the establishment of autocrine feedforward circuits, should also be envisioned.

Figure 2

Stem cell exposure to magnetic energy leads to targeted lineage specification. As shown in the diagram, exposure of undifferentiated mouse embryonic stem cells (GTR1 cell line) to extremely low frequency magnetic fields primes the transcription of cardiac lineage promoting genes and the synthesis and secretion of dynorphin B, acting as an orchestrator of signaling and gene expression patterning required for the appearance of a myocardial phenotype (for details see the section ‘Magnetic fields and stem cell differentiation: a novel frontier in phenotyping design’). Cardiomyocytes (lower panel) express cardiac-specific markers, including α-myosin heavy chain (α-MHC) and myosin light chain-2V (MLC). (α-MHC is stained green with the MF 20 mouse antimyosin monoclonal antibody; DNA is visualized with prospidium iodide. Bio-Rad Microradians confocal microscope, ×20 objective.)