الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Mesenchymal stem cells are nonhaematopoietic stem cells, which are able to differentiate into a variety of cell types, including osteocytes, chondrocytes and adipocytes.
MSCs can be isolated from bone marrow, adipose tissue, skeletal muscle, synovium, the circulatory system, peripheral blood, dental pulp, liver, lung, amniotic fluid, placenta and umbilical cord.
MSCs have multiple criteria as Adhesion properties to plastic under standard tissue, Expression of certain cell surface markers and differentiation capacity into osteoblasts, adipocytes, and chondroblasts.
Immunomodulatory property of MSCs. MSCs can target lymphocytes, regulatory T-lymphocytes (Tregs), B-lymphocytes, Plasma cells, Natural killer (NK) cells, neutrophils, mast cells, monocytes, and dendritic cells. These effects may be mediated by cell contacts, soluble factors and MSC-derived EVs.
MSCs can be isolated through procedures involving tissue mincing, enzymatic digestion, and cell growth on a plastic surface. The two main procedures are the enzymatic and explant protocols.
MSC selection is the first consideration, it was needed to investigate whether infused MSCs could occur systemic or local immune responses. MSCs were proved to avoid recipients’ immune surveillance. other factors that affect the therapeutic potential, including the age of the donor. The infusion of aged MSC would rather deteriorate the disease severity. Another strongly suggested problem is the individual difference between MSCs based on the variable backgrounds from donor to donor.
Trying to fine-tune the features of the cells to be suited for the targeted diseases before cell application. Manipulating the features of MSCs include cytokines/chemokines, growth factors, receptor agonists, hormones, drugs, and hypoxic environment.
The pretreatment of bioactive molecules and hypoxia, modification of cell culture such as 3-dimensional (3D) method holds the great possibility to improve the stemness and therapeutic potential of MSCs.
Genetic modification of MSCs can be employed to improve the therapeutic potency of MSCs independently with exogenous stimuli.
Co-administrative assistant substances to increase the therapeutic function of MSCs as immunosuppressants and genetic manipulation.
Co-application of MSCs with immunosuppressants including rapamycin and tacrolimus showed improved therapeutic outcomes through the synergism of each remedy, by which improving the survival time in the transplantation of MSCs and reducing the adverse effects of medicines.
Potential mechanism of neoplastic transformation in some cases of MSC transplantation.
MSCs exert significant effects on immunosuppression by refraining immune cells in both the innate and adaptive immune systems.
MSCs exert therapeutic effects in numerous diseases such as graft versus host disease (GVHD), liver failure, acute myocardial infarction, liver cirrhosis and autoimmune diseases such as SLE, rheumatoid arthritis, crohn’s disease, type 1 DM and MS.
The clinical trials based on MSC-mediated therapies is outstripping the progress in its basic research, presenting a great challenge of establishing guidance but also creating an opportunity to deepen our understanding of therapeutic MSCs. To achieve optimal stability, tolerability, and performance of next-generation MSCs therapies.