Connective Tissue Of Organs Research Articles

Intravenous Injection of Muse Cells as a Potential Therapeutic Approach for Epidermolysis Bullosa

Intravenous Injection of Muse Cells as a Potential Therapeutic Approach for Epidermolysis Bullosa

Removing Barriers to Regenerative Medicine And Promoting Innovative Applications: The Discovery Of Human Endogenous Pluripotent Muse Cells

Multilineage-differentiating stress-enduring (Muse) cells are naturally existing, non-tumorigenic reparative endogenous stem cells identified by SSEA-3 expression. Muse cells are able to differentiate into nearly all cell types in the body, mobilize from the bone marrow to the peripheral blood and distribute to the connective tissue of organs, and contribute to daily minute repair of damaged/lost cells by spontaneous differentiation into tissue-compatible cells. Endogenous Muse cells express receptors for damage signaling by sphingosine-1-phosphate and are thus able to specifically home to sites of damage to regenerate healthy tissue by simultaneous differentiation into multiple tissue-constituent cells. When the number of endogenous Muse cells is not sufficient, administration of exogenous Muse cells delivers robust functional recovery. Muse cells do not need to be "induced" or genetically manipulated to exhibit pluripotency or to differentiate into various cell types for clinical use. Intravenous drip is the main method of administration, making surgery unnecessary. Furthermore, because Muse cells have an immunomodulatory system similar to the placenta, donor-derived Muse cells can be directly administered to patients without human leukocyte antigen-matching or immunosuppression therapy. Clinical trials for the treatment of myocardial infarction, stroke, and epidermolysis bullosa by intravenous delivery of donor-derived Muse cells are currently being conducted by the Life Science Institute Inc., a member of the Mitsubishi Chemical Holdings Corporation. Overall, Muse cells may safely provide clinically relevant regenerative effects compatible with the 'body's natural repair systems' by a simple, cost-effective strategy—collection of Muse cells, large-scale expansion, and intravenous administration.

Muse cells, newly found non‐tumorigenic pluripotent stem cells, reside in human mesenchymal tissues

Mesenchymal stem cells (MSCs) have been presumed to include a subpopulation of pluripotent-like cells as they differentiate not only into the same mesodermal-lineage cells but also into ectodermal- and endodermal-lineage cells and exert tissue regenerative effects in a wide variety of tissues. A novel type of pluripotent stem cell, Multilineage-differentiating stress enduring (Muse) cells, was recently discovered in mesenchymal tissues such as the bone marrow, adipose tissue, dermis and connective tissue of organs, as well as in cultured fibroblasts and bone marrow-MSCs. Muse cells are able to differentiate into all three germ layers from a single cell and to self-renew, and yet exhibit non-tumorigenic and low telomerase activities. They can migrate to and target damaged sites in vivo, spontaneously differentiate into cells compatible with the targeted tissue, and contribute to tissue repair. Thus, Muse cells may account for the wide variety of differentiation abilities and tissue repair effects that have been observed in MSCs. Muse cells are unique in that they are pluripotent stem cells that belong in the living body, and are thus assumed to play an important role in 'regenerative homeostasis' in vivo.

Abstract 536: Mesenchymal stromal cells promote tumor growth both in vitro and in vivo

Abstract [Background] Mesenchymal stromal cells (MSCs), also referred as mesenchymal stem cells are pluripotent progenitor cells that differentiate into chondrocytes, adipocytes, osteoblasts and other types of cell. Although MSCs are resident mainly in bone marrow, MSCs are found in adipose tissue, lung, and many other organs where MSCs maintain and regenerate the connective tissues of organs. Recent report proposed that MSCs also migrate and function as stromal cells in the tumor tissues. Effects of MSCs on tumor growth in vitro and in vivo are still unclear. In this study, we verified tumor promotion by MSCs and analyzed mechanisms. [Method] B16-LacZ, a melanoma cell line expressing β-galactosidase protein, was tested for their growth rate by X-gal colorizing assay in the presence or absence of mouse bone marrow MSCs in vitro. Growth of B16-LacZ was also examined in the detached condition using cell disk or conditioned medium from MSCs. Next, B16-LacZ and Lewis Lung Carcinoma (LLC) cells were mixed with MSCs at 1/1 and 1/5 ratios and subcutaneously inoculated into mice. Tumor sizes were measured and immunostaining of CD31 was performed to evaluate angiogenesis. We also determine the secretion of soluble factors associated with angiogenesis in cultured medium from B16-LacZ alone, MSCs alone, or B16-LacZ and MSCs ELISA. [Result] Proliferation of B16-LacZ co-cultured with MSCs exhibited 5.8 times greater than that of B16-LacZ alone in vitro (P<0.01). In detached condition, using cell disk or conditioned medium from MSCs, the growth rate was only 1.6 times (P<0.01) in cell disk, and 1.4 times (P<0.05) in conditioned medium at 60-hour incubation. Mixed group of B16-LacZ and MSCs at 1/1 and 1/5 ratios developed 2.3 times (P<0.05) and 4.3 times (P<0.01) grater tumor compared to B16-LacZ alone in vivo. MSCs alone did not develop a tumor. Results of LLC experiments were similar to B16-LacZ experiments. Tumor vessel area of mixture of B16-LacZ and MSCs was 2.4 times (P<0.05) at 1/1 and 4.2 times (P<0.01) at 1/5 ratio lager than B16-LacZ alone. The amount of the secretion of LIF, M-CSF, MIP-2 and VEGF factors from MSCs were significantly larger compared with B16-LacZ. The amount of the secretion from co-culture of B16-LacZ and MSCs was almost the same as the MSCs alone group. [Conclusion] MSCs promoted tumor growth both in vitro and in vivo, and promotion of tumor growth by MSCs can be at least in part attributed to the tumor angiogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 536.

Functions of optic nerve glia: axoglial signalling in physiology and pathology

An early concept of glial function envisaged them as passive and unexcitable structural elements, much like the connective tissues of organs in the periphery. It is now known that glia have a widespread range of physiological roles and react to all forms of pathological insult. This paper reviews the major functions of oligodendrocytes and astrocytes, the main types of glia in the optic nerve, and examines novel NG2-glia, otherwise known as oligodendrocyte progenitor cells (OPCs). The major function of oligodendrocytes is to produce the myelin sheaths that insulate CNS axons, but they also have important roles in the establishment of nodes of Ranvier, the sites of action potential propagation, and axonal integrity. Astrocytes have multiple physiological and pathological functions, including potassium homeostasis and metabolism, and reactive astrogliosis in response to CNS insults. The bulk of NG2-glia are postmitotic complex cells, distinct from OPCs, and respond to any insult to the CNS by a rapid and stereotypic injury response. This may be their primary unction, but NG2-glia, or a subpopulation of NG2-expressing adult OPCs, also provide remyelinating oligodendrocytes following demyelination. Oligodendrocytes, astrocytes, and NG2-glia all contact axons at nodes of Ranvier and respond to glutamate, ATP, and potassium released during axonal electrical activity. Glutamate and ATP evoke calcium signalling in optic nerve glia and have dual roles in physiology and pathology, coupling glial functions to axonal activity during normal activity, but enhanced activation induces an injury response, as seen following injury, demyelination, and ischaemia.

Perisinusoidal stellate cells of the liver: important roles in retinol metabolism and fibrosis

In mammals, liver perisinusoidal stellate cells play an important role as a main store of body retinol (vitamin A). This fat-soluble vitamin is essential for vision, and regulates differentiation and growth of many cell types during embryonal development as well as in adult tissues. Thus, many cell types require a continuous supply of retinol. The storage of retinol (as retinyl esters) in stellate cells ascertains ample access of retinol to such cells also during periods with a low dietary intake. In lower vertebrates such as fish, vitamin A-storing stellate cells are found not only in the hepatic lobule, but also in the connective tissues of organs like intestine, kidney, ovaries, testes, and gills. Extrahepatic vitamin A-storing stellate cells are found in higher vertebrates when excessive doses of vitamin A are administered. It is not clear at present whether these cells also play a role in retinol metabolism under normal conditions. Stellate cells proliferate in a fibrotic liver, and they have been found to synthesize connective tissue compounds such as collagen. It was recently demonstrated that stellate cells are the principal cellular source of collagen and other extracellular substances in normal as well as fibrotic livers. Therefore, stellate cells, which seem to be a specialized type of pericyte, have a central role in the pathological changes observed during the development of liver fibrosis.