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The Role Of Human Umbilical Cord Mesenchymal Stem Cells In The Treatment Of Alzheimer 's Disease Cell Model And Its Mechanism

Posted on:2017-05-11Degree:MasterType:Thesis
Country:ChinaCandidate:J L ZhaiFull Text:PDF
GTID:2174330488957965Subject:Pathology and pathophysiology
Abstract/Summary:PDF Full Text Request
Alzheimer’s Disease (AD) is a neurodegenerative disorder as we known as a intractable disease, which is the main reason of dementia in aging. Until now, there is no definitely straightforward pathogen to this disease, but 30 kinds of hypothesis including inherence, gender, brain trauma, lower degree of education, thyroid disease, childbearing age, and virus infection. AD is characterized by amyloid β plaques and neurofibrillary tangles (NFTs). The latter feature is caused by hyperphosphorylated Tau, which also results in the disposition of plaques and occurrence of inflammation of neurons. The main clinical syndromes of AD are dysfunction of cognition, decreased memory and object cognitive capability which all rescue the living quality of patients and their relatives. There have been 18,000,000 patients about AD, and this number will increase by the longevity of population. So the discovery of therapeutic method of AD is extremely urgent. From now on, there have been many kinds of drugs to alleviate the syndromes of AD, but no one can be sure to have the function to control the progress of diseases, improve the cognitive capability of patients and even guarantee a better prognosis. The current situation not only provide perplex to AD patients but also to scientists. But it’s also a favorable chance to find out some new approaches.Many kinds of stem cells treatment provide much good news to diseases with aging progress. Stem cells therapy is an advantage medicine technique whose main method is the transplantation of stem cells into the body of patients by some way, and following the transplantation, stem cells can replace the injury cells or organs by different mechanism. Meanwhile, stem cells have the characteristic about aboard source, so that these can be and have been used in different range of diseases like neural diseases, immune system diseases and blood cells diseases. Stem cells are called "almighty cells" in medicine, that means the knowledge of potential ability of stem cells can be discovered and move forward a big stride.Should the stem cells therapy be used in AD? As the current situation of studies, this method is feasible. Several researches and clinic trails have improved that stem cells have the therapeutic effects to many neural diseases including AD. Targeting to AD, many kinds of stem cells are candidates, like mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs). Although the NSCs, ESCs and iPSCs have the effects to AD model in vivo and vitro, the disadvantages about which include the limited sources, the difficulty to isolate, the low rate of proliferation, immune rejection and limitation from ethic, make the clinic trail of those hard to progress. But the studies about MSCs are abundant and the current researches not only include experiments in lab but also clinic trails. MSCs may be the candidate as they have functions like regulation of immune, multi-directional differentiation, micro-environment regulation, neurotrophy, and so on. All of these functions may be the mechanism of MSCs to cure or prevent neural diseases like AD by regulating the microenvironment of neurons and immune response or differentiating towards neural cells. Many sources of MSCs like dental pulp, umbilical cord and its blood, adipose tissue, bone marrow, placenta and so on, have the capacity to cure AD. These researches affirm the therapeutic effects and discover the advantages of MSCs to neural diseases whose mechanisms may be rely on the regulation of immune, multi-differentiation, modulation of micro-environment and so on. All these mechanisms are associated to paracrine and secretion of MSCs, and also the potential mechanisms to neural diseases treatment.In all sources of MSCs, human umbilical cord deprived MSCs (hUC-MSCs) has been identified to have effect to treat the neural diseases including AD. hUC-MSCs are deprived from discarded tissue after delivery. Compared with other sources of MSCs, hUC-MSCs have more advantages like the easy way to obtain and isolate, the high rate of propagation, and the more capable ability to differentiate. Meanwhile, there have been two registrations on clinic trail webnet. That confirms the superiority and feasibility of hUC-MSCs.But, the mechanism of treatment is without understanding. Researchers suspect that it may be via the secretion of hUC-MSCs, because it take part in the regulation of immune, nutrition support, improvement of differentiation and angiogenesis, modulation of microenvironment and so on. Here come the questions:what can be secreted by hUC-MSCs? Which is the key one in the treatment of AD?Here, we modeled the AD cell model by OA and cell line of neuroblastoma SH-SY5Y as OA has the injury function to SH-SY5Y. Then we used the condition medium of hUC-MSCs (hUC-MSCs-CM) to treat the impaired cells. With the assurance of this remedy, we screened the secreted factors of hUC-MSCs, and discussed the key factors which play the key role in the treatment method. By understanding of the high value factors and some experiments based on the cell model, we understood the IL-6 and HGF are the super factors of hUC-MSCs and via the treatment function to AD.The meanings of our study are including the following two aspects. Firstly, we improve the therapeutic effect of the secretion of hUC-MSCs in AD ex vivo. Secondly, we affirm the therapeutic effect is via the secretion of IL-6 and HGF.The application prospect of our study is very wide. As AD, we can develop special kinds of hUC-MSCs with IL-6 or HGF overexpression to treat AD. We can also combine the two factors to treat AD with proper dose and scale. As hUC-MSCs, based on the secretion spectrum of hUC-MSCs, we can discover other mechanisms of treatment effect of diseases, and make the feasible of hUC-MSCs treatment more extended.
Keywords/Search Tags:Alzheimer’s disease, hUC-MSCs, cell model, IL-6, HGF, hyperphosphorylated Tau, cytoskeleton
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