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Myogenic Differentiation Strategies And Related Mechanisms Of Bone Marrow Derived-mesenchymal Stem Cells

Posted on:2004-07-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:J WangFull Text:PDF
GTID:1104360095461236Subject:Military Preventive Medicine
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Skeletal muscle represents the largest tissue mass in the body, constituting 40% to 45% of total body weight. It is a composite structure consisting of muscle cells, organized networks of nerves and blood vessels. There always companion muscle damages in serious injuries such as traffic accident injuries, shooting injuries and burn injuries, so do in some of internal diseases such as diabetes, tumor and paralysis. Serious muscle injuries can directly induce the losing of the exercise function and effect on the function of the nerve and blood vessel systems. Satellite cells (SC) are in charge of the muscle regeneration, but the number of SC is low and goes on to descend with the age. So, SC can not repair serious and mass muscle injuries, damaged tissues are substituted by the fiber tissues and form scars at last, howerer, this results should lead to serious injuries. It's an important task to select suit seed cells to adhere on the biology materials so as to promote the repair of muscle injuries. Some scholars seeded SC on polyglycolic acid (PGA) and transplanted into the abdominal cavity omentum,it could form the functional muscle tissues with blood vessels in PGA 30-40d later. But the shortages of SC such as the damnification on the body in the course of collecting, difficulty in acquirement and low number will limit their application. Mesenchymal stem cells (MSCs), derived from the mesoderm, are capable of multi-differentiating, potential to differentiation into marrow stromal cells, osteoblasts, chondrocytes, lipocytes, myoblasts and neurocytes, are easy to be isolated and cultured in vitro. Wakitani first reported that 5-azacytidine (5-Aza-CR) could induce MSCs to differentiate into myoblasts in 1995 which is the base to research the myogenic differentiation, but the related mechanisms are not reported.The differentiation process of myoblasts is regulated by myogenic regulatory factors (MRFs), which is a kind of transcription factors called as myogenic basic helix-loop-helix (bHLH) including Myf5,MyoD,myogenin and MRF4, MRFs genes can activate the non-myoblasts to differentiate into myoblasts when they are expressed in these cells, so, maybe it is the differentiation premise when MRFs are induced to express in MSCs effected by 5-Aza-CR.The differentiation process of stem cells is actually the process that cells answer the stimulating signals, start up and carry up the signal transduction. The transduction processin cells stimulated by activated signals is too the proliferation and differentiation premise, however, we think it should be very significance to realize signal transduction pathways in the course of cells' differentiating, and it will help us to illustrate the gene regulated mechanisms, promote the directional differentiation via promoting these pathways. Mitogen activated protein kinase (MAPK) is very important in the course of transducting the signals from the cells surface to the internal, which includes extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), stress-activated protein kinase p38 and ERK5. It has been confirmed phosphatidylinositol 3-OH kinase (PI3K) is a positive signal transduction pathway in the course of maturation and differentiation of SC. PI3K can activate the down transcription factor Akt and promote the differentiation of SC, but there are no related reports on the myogenic differentiation of MSCs. Many factors have important effect on the proliferation and differentiation, insulin-like factor-I (IGF-I) can obviously enhance the signal transduction in the myogenic differentiation course of SC and promote the differentiation process, how about in that of MSCs is not known, however, it should be very important to understand these mechanisms in investigating the theory about myogenic differentiation of MSCs and applying these cells in muscle injury repair.SC is quiescence in normal but activated in stress, express MRFs and begin to myogenic differentiation. SC expresses MyoD or Myf5 after 3-12h when stimulated, but what is the virtually...
Keywords/Search Tags:Bone marrow, Mesenchymal stem cells, Myoblast, Muscle injury, Myogenic regulatory factors, Myogenic regulatory factor 5, Myogenin, Inducement, Proliferation, Differentiation, Insulin-like growth factor-I, Singal transduction
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