Neuropathogenesis-on-chips for neurodegenerative diseases:
Developing diagnostics and treatments for neurodegenerative diseases (NDs) is challenging due to multifactorial pathogenesis that progresses gradually. Advanced in vitro systems that recapitulate patient-like pathophysiology are emerging as alternatives to conventional animal-based models. In this review, we explore the interconnected pathogenic features of different types of ND, discuss the general strategy to modelling NDs using a microfluidic chip, and introduce the organoid-on-a-chip as the next advanced relevant model. Lastly, we overview how these models are being applied in academic and industrial drug development. The integration of microfluidic chips, stem cells, and biotechnological devices promises to provide valuable insights for biomedical research and developing diagnostic and therapeutic solutions for NDs.

Cell-based therapy to treat Type I Diabetes Mellitus has been studied and several methods are practically introduced to clinics, and transplantation of healthy allogeneic beta-cells has played reliable results, while consistency of maintaining blood-glucose level, escaping immunological problems, and oncogenesis are generally concerned topics after delivering therapeutic cells into patients. It has been recognized that applying autologous cells are ideal to avoid immunologically oriented problems. Viable multupotent mesenchymal cells are proven to be differentiated toward beta-cells releasing insulin molecules if appropriate niche was provided, while it requires delayed period to reveal biological functions until the delivered cells are properly adapted to the new niche. To reduce the manifesting time, transfecting preproinsulin gene into mesenchymal cell has been studied, but possibility of oncogenesis after transplantation is an unsolved intrinsic problem by using growth factors which also propel differentiation of the mutated cells. To resolve this problem, preparation of mesenchymal cells to release insulin in a culture media by providing controlled niche without using growth factors, and compared them with preproinsulin gene transfected cells in vitro and in vivo.

We have developed a new technique for direct isolation of human placenta stromal cells from tissues of fetal origin (fPSC) by a unique process which allows the direct migration of the desired cells from tissue fragments to culture dishes for further expansion. The resultant selected placental stromal cell population was found to indirectly enhance the regeneration of failing bone marrow and to mitigate of acute radiation syndrome (ARS) following total body irradiation. IM treatment by fPSC showed that these stromal cells were more immunocompetent and could reside longer in the injected muscle with no apparent adverse effects associated with IV delivery of MSC of different origin. In studies on mitigation of radiation effects these cells enabled to repopulate the failing bone marrow lineages with subsequent regeneration of the peripheral blood cells. This saved the treated animals from the lethal effects of ARS with dramatic significant raise of the survival in ~8Gy irradiated mice from less than a third to almost 100% with a fast recovery of the bone marrow and the peripheral blood cell lineages. Detailed cytokines analyses showed that the injected xenogeneic cells respond to the stress of the high dose irradiation by the secretion of a wide range of related pro-regenerative cytokines and growth factors including GM-CSF, GCSF, IL-6, GRO, MCP-1, all associated with the regeneration of the hematopoietic systems and other regenerative processes. The IM based fPSC treatments have also been investigated as cell therapy for bone marrow failure due to different other causes. Other indications are tested for the PSC treatment, to help the regeneration of various tissues and organs affected by autoimmune diseases. These include inflammatory bowel disease (IBD) and autoimmune inflammatory processes in the brain, such as an EAE model of multiple sclerosis. Further detailed studies are in progress to better understand the indirect mechanism of action of the PSC by stress induced activation of relevant family of genes.

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MiR-206 inhibits estrogen signaling and ovarian cancer cell migration without affecting GPER