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العنوان
Stem cells in liver diseases :
المؤلف
Borg, Asmaa Mohamed Abd El-Ghaffar.
هيئة الاعداد
باحث / Asmaa Mohamed Abd El-Ghaffar Borg
مشرف / Ekbal Mohamed Abo Hashem
مشرف / Gamal Kamel El-Ebidy
مشرف / Ziyad Mohamed Essam El-Din Tawhid
الموضوع
Stem cell-- Therapeutic use.
تاريخ النشر
2012.
عدد الصفحات
130 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الطب
تاريخ الإجازة
1/1/2012
مكان الإجازة
جامعة المنصورة - كلية الطب - Clinical Pathology
الفهرس
Only 14 pages are availabe for public view

from 159

from 159

Abstract

The ability of stem cells to self-renew and give rise to subsequent generations with variable degrees of differentiation capacities, offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects. There are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells. Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, liver diseases, metabolic diseases, Parkinson’s disease, Huntington’s disease, celiac disease, cardiac failure, muscle damage and neurological disorders, and many others. Liver pathologies affect hundreds of millions of patients worldwide. The most common causes of hepatopathy are chronic hepatitis C and B, alcoholism, nonalcoholic fatty liver disease, autoimmune, and drug-induced hepatic disorders. Many of these conditions can be prevented or treated, but if not, they can lead to progressive liver injury, liver fibrosis and ultimately cirrhosis, portal hypertension, liver failure, and, in some instances, cancer. End stage liver disease (ESLD) is an irreversible condition that leads to the eventual failure of the liver. It may be the final stage of many liver diseases, for example, viral hepatitis, autoimmune hepatic disorders, fatty liver disease, drug induced liver injury, and hepatocellular carcinoma, with extremely poor prognosis. The incidence of ESLD is increasing worldwide, and current optimal treatment for ESLD is orthotopic liver transplantation. However limited availability of donor livers and immunological incompatibilities and high cost are the major obstacles to its routine deployment. This highlights the important need for alternative therapeutic strategies. Extra-corporeal support has been proposed as a mid-term strategy, in particular bio-artificial livers, to treat human liver disease. Bio-artificial livers (BALs) are designed to filter and biotransform toxic substances, and have been used successfully to bridge patients to transplant or treat acute liver failure. Research demonstrates that BALs can reduce mortality in acute liver failure compared with traditional standard medical therapy, but the application has been severely limited by the poor availability of functional human hepatocytes. In view of these shortfalls there is clearly still an urgent need to develop alternative strategies for the treatment of advanced liver disease and cell-based hepatocyte transplantation is of particular interest and believed to hold great promise because of the simpler and less invasive procedure. A single donor could serve multiple recipients, and excess cells could be cryopreserved for future use. There are four main types of stem cell transplants depending on where the stem cells come from. This types are autologous transplants (patients receive their own stem cells), syngeneic transplants (patients receive stem cells from their identical twin), allogeneic transplants (patients receive stem cells from their brother, sister, parent or a person who is not related to the patient) and xenogenic transplants (from animal sources). The cell transplants used for liver diseases include hepatocytes, stem or progenitor cells, xenogenic hepatocytes and modified cells. The use of hepatocytes is limited by lack of donated hepatocyte sources, deterioration of their function after storage or culturing and by their limited proliferation potential. The stem or progenitor cells can overcome this shortfalls as their sources are readily available and they can be widely expanded in vitro and in vivo. Stem cell sources include liver progenitor (oval cells), embryonic stem cells, fetal liver stem cells, umbilical cord & placental stem cells and adult stem cells (present in various adult tissues as B.M., adipose tissue & others. Stem cells can be characterized by either their characteristic surface markers (CD markers) and also by their molecular definition. Isolation (separation) of stem cells can be done using conventional methods (like sedimentation, capture on solid beads or ficoll-hypaque centrifugation), flowcytometry, magnetic cell sorting and fully automated stem cell separators. Stem cells could be infused directly into the liver or the nearby vascular systems (portal vien & hepatic artery). The other sites include spleen, kidney capsule, peritoneum and fat pad. Owing to the importance of extracellular environment there was an interest to compine the stem cells with a biodegradable scaffolds that can be synthesized from natural or synthetic materials. This can maintain stability of stem cells and support their functions by facilitating cell-cell interaction and by facilitating cell growth. Especially in 3D manner of scaffolds which resmple the normal hepatic architecture which is important for hepatocytes function. There are also an interest in providing suitable culture conditions for stem cells and providing adequate vascularization for growing stem cells. The use of emberyonic stem cells has advantage over adult stem cells being having greater differentiation potential but their use is limited by its oncogenic potential as well as the ethical concerns around their use. It has been called the age of stem cells, the seemingly magic root cells of life that can be used to generate almost every other type of cell, possibly opening a door to a new world of regenerative therapy. A better understanding of liver regeneration and stem cell biology could be applied clinically to improve the treatment of liver disease. Despite the overall positive potential of stem cell therapy, some important theoretical and practical issues have to be addressed before stem cell transplantation becomes a routine procedure for the treatment of liver disease. For example, we need additional studies about: Finding additional sources of hepatocytes. Maintaining viable hepatocytes in stem cell therapeutic application. Cryopreservation, or storage of the stem cells. The route of cell application. Engraftment, or “homing” of cells to the diseased tissue.