Phlorotannin-incorporated Mesenchymal Stem Cells and their Promising Role in Osteogenesis Imperfecta

Article (PDF Available)inIranian Journal of Medical Hypotheses and Ideas 6(2):85–89 · July 2012with53 Reads
DOI: 10.1016/j.jmhi.2012.09.002
Abstract
Osteogenesis imperfecta as the name suggests, is a bone disorder characterised by imperfect bone mineralisation and development. The key defect lies in the osteoblast–osteoid cycle, leading to insufficient calcification and consequently weak bones. Osteogenesis imperfecta patients are prone to fractures. Till date, numerous growth hormone/synthetic analogues have been used therapeutically in osteogenesis imperfecta patients and they do provide temporary relief, but not without numerous unwanted side effects. The intervention offered by such treatments is mainly at the symptomatic level, with temporary pain relief and some degree of mineralisation of available osteoids; but the root cause of the disease remains unattended. Such treatment modalities fail to promote mesenchymal stem cell osteogenic differentiation and tackle the fundamental deficiency of osteoids. This paper suggests a unique and hitherto unimplemented approach for treatment of osteogenesis imperfecta at the cellular level through application of a natural source, ‘Brown algae isolated phlorotannins’, which promote mesenchymal stem cell differentiation by increasing alkaline phosphatase activity, calcific mineralisation and total protein and collagen synthesis. This natural extract, when integrated directly with mesenchymal stem cells, will boost cellular differentiation into healthy bone-forming cells. The modality will strengthen the bone intrinsically and without the adverse reactions of routine pharmacotherapeutic agents.

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    • "Many companies produce recombinant cytokines using Escherichia coli cells, plant cells, and other mammalian cells. Yet, the recombinant and synthetic cytokines, growth factors, and other proteins involved in the proliferation and differentiation of stem cells used in cell culture and in clinical treatment may show side effects and toxic effects [31] when used continuously and the stem cells may have the potential for rejection due to the different origins of the stimulants. Ascorbic acid used for osteogenic differentiation is unstable at 37 °C and toxic at high doses [32] . "
    [Show abstract] [Hide abstract] ABSTRACT: Stem cell therapy has revolutionized modern clinical therapy with the potential of stem cells to differentiate into many different cell types which may help to replace different cell lines of an organism. Innumerous trials are carried out to merge new scientific knowledge and techniques with traditional herbal extracts that may result in less toxic, affordable, and highly available natural alternative therapeutics. Currently, mesenchyamal stromal cell (MSC) lines are treated with individual and mixtures of crude herbal extracts, as well as with purified compounds from herbal extracts, to investigate the mechanisms and effects of these on stem cell growth and differentiation. Human MSCs (hMSCs) possess multilineage, i.e., osteogenic, neurogenic, adipogenic, chondrogenic, and myogenic, differentiation abilities. The proliferative and differentiation properties of hMSCs treated with herbal extracts have shown promise in diseases such as osteoporosis, neurodegenerative disorders, and other tissue degenerative disorders. Well characterized herbal extracts that result in increased rates of tissue regeneration may be used in both stem cell therapy and tissue engineering for replacement therapy, where the use of scaffolds and vesicles with enhanced attaching and proliferative properties could be highly advantageous in the latter. Although the clinical application of herbal extracts is still in progress due to the variability and complexity of bioactive constituents, standardized herbal preparations will strengthen their application in the clinical context. We have critically reviewed the proliferative and differentiation effects of individual herbal extracts on hMSCs mainly derived from bone marrow and elaborated on the plausible underlying mechanisms of action. To be fruitfully used in reparative and regenerative therapy, future directions in this area of study should (i) make use of hMSCs derived from different non-traditional sources, including medical waste material (umbilical cord, Wharton’s jelly, and placenta), (ii) take account of the vast numbers of herbal extracts used in traditional medicine globally, and (iii) investigate the mechanisms and pathways of their effects on hMSCs.
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    • "These compounds could also have some antidiabetic (Lee & Jeon, 2013), antimicrobial (Eom, Kim, & Kim, 2012), antioxidant, anticancer and radioprotective (Liu, Hansen, & Lin, 2011) together with anti-inflammatory effects (Kang, Eom, & Kim, 2013; Kim, Shin, et al., 2009 ). Moreover, studies have shown that phlorotannin derivatives increase alkaline phosphatase activity, mineralisation, total protein and collagen synthesis in human osteosarcoma cells (MG- 63 cells) (Ali & Hasan, 2012; Ryu, Li, Qian, Kim, & Kim, 2009; Yeo, Jung, & Kim, 2012). These results suggest that phlorotannins could stimulate the osteoblast differentiation and regulate osteosarcoma differentiation, with an implication of phenolic compounds in the mitogen-activated protein kinase pathway (Ryu et al., 2009). "
    [Show abstract] [Hide abstract] ABSTRACT: Phlorotannins are metabolites synthesised by brown algae to protect against environmental stresses. Only a few studies presented structural elucidation of native molecules extracted from macroalgae, contrary to previous published studies, which characterised acetylated phlorotannins. The present work introduces quantitative and qualitative studies to characterise phlorotannins from the eight species of Sargassaceae settled in Brittany, using a colorimetric method used for quantification of total phenolic content (TPC), and one- and two-dimensional nuclear magnetic resonance (NMR) (1H, heteronuclear multiple bond correlation) together with in vivo NMR (high-resolution magic-angle spinning (HR-MAS) NMR) analyses, with the aim to elucidate structural and fingerprint of phlorotannins signals. Halidrys siliquosa, which settles in low tide rock pools, exhibited high TPC (17.77±1.68% dry weight (DW)) while the other species showed lower TPC (ranged from 0.85±0.11% DW for Cystoseira baccata growing in low tide rock pools to 5.53±0.63% DW in Cystoseira humilis growing in high tide rock pools). No relation between TPC and the position of the algae along the shore could be highlighted. Fingerprints using NMR HR-MAS were useful to compare the eight species in terms of phenolic content and in terms of phenolic signals as the species from Brittany produced different phlorotannins. Our study demonstrated that Cystoseira tamariscifolia produced the monomer (phloroglucinol), C. humilis, phloroglucinol and a phlorethol, C. baccata and Cystoseira nodicaulis produced many compounds, i.e. traces of phloroglucinol together with fucols, phlorethols, and fucophlorethols and finally fuhalols were identified in Bifurcaria bifurcata and H. siliquosa. The putative ecophysiological roles of these phlorotannins from Sargassaceae are discussed, together with their potential bioactivities.
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    [Show abstract] [Hide abstract] ABSTRACT: This article reflects the comparison of downloads, readership and citation data for the Journal of Medical Hypotheses and Ideas. A brief analysis of the journal’s recent performance indicates that the journal articles appear to have a high rate of downloads around the world. Its published articles are from a variety of countries and the odds of accepted articles for publication is surprisingly even across regions. However, the rate of received citations to the published articles indicated a lack of considerable impact in scholarly publications. This approach has double value as it shows the overall impact of the journal in social web as well as scholarly publications and also provides future directions for the journal’s editorial boards. Altmetrics was also proposed as an alternative to the widely used citation and usage indicators in tracking the impact of individual articles.
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