9.8. Cardiovascular diseases

been found in the cerebral cortex, olfactory lobe, hippocampus and brain stem, suggesting that MSCs could successfully survive and proliferate in vivo [66]. Moreover, this type of administration was observed to increase the level of tyrosine hydroxylase and decrease the toxin 6 hydroxydopamine in the ipsilateral striatum and substantia nigra lesions. This novel MSCs

Alzheimer disease (AD), one of the commonest neurodegenerative diseases, characterized by symptoms as intellectual disabilities, dementia and memory loss. Till present, no treatment was established to slow down or stop the progression of AD [67]. Researchers use stem cell therapy in AD animal model aiming to decrease the neuropathological deficits. Mostly by activating the alternate microglia, increasing the expression of Aβ-degradation enzymes and decreasing the expression of pro-inflammatory cytokines, that the human AD-MSCs modulate the inflammatory environment [68]. Furthermore, MSCs modulate the inflammatory environment of AD and inadequacy of regulatory T-cells (Tregs) and they could modulate microglia activation [69]. Shin et al. [70] demonstrated that human UCB-MSCs increase the neuronal survival and stimulate Tregs which control microglia activation in AD mice model. Most recently, it was confirmed that MSCs stimulates the cell autophagy pathway, causing increased neuronal survivability and clearing of the amyloid plaque both in vivo and in vitro [70].

MSCs have the ability of regulating immune responses, thus it can treat immune disorders. Other hMSCs can be used for autoimmune diseases treatment, after revealing that human BM-

Rheumatoid arthritis (RA), a joint inflammatory disease resulting from loss of immunological self-tolerance. The use of MSCs in animal models' studies, were successful in slowing disease progression and enhancing the disease recovery. Beside its anti-inflammatory function, IL-10 is an important factor in the activation of Tregs that controls self-reactive T-cells and motivates peripheral tolerance in vivo [72]. Similar effects were produced by human BM-MSCs in the collagen-induced arthritis model in DBA/1 mice [73]. These studies suggest that the improvement of the RA pathogenesis in DBA/1 mice model in case of using MSCs, can be caused by activating Treg cells as well as suppressing the production of inflammatory cytokines. However, MSCs were only effective when administered at the onset of disease, in case of adjuvantinduced and spontaneous arthritis model, which suggests that MSCs lost their immunoregu-

Type 1 diabetes, an autoimmune disease caused by the destruction of β-cells due the production of auto antibody directed against these cells. As a result, there is decrease in the insulin

MSCs are able to protect hematopoietic precursors from inflammatory damage [71].

latory properties when exposed to inflammatory microenvironment [74].

administration route could change the face of MSCs transplantation in future.

9.4. Alzheimer disease

14 Stromal Cells - Structure, Function, and Therapeutic Implications

9.5. Autoimmune diseases

9.6. Rheumatoid arthritis

9.7. Type 1 diabetes

Cardiac cells transplantation is a novel strategy for myocardial repair, which is currently applied in animal models. Although MSCs are a good source for cardiomyocytes differentiation, it was found that in vitro differentiation is effective only from young cell sources and in vivo differentiation of cardiomyocytes is very rare [81]. MSCs, which have differentiated into cardiomyocytes under the effect of cocktail of growth factors [82], were used in treatment of left ventricular heart failure and MI [83]. The systematic injection of BM-MSCs into the infarcted myocardium of rodent models partially produced recompensation [84]. Katritsis et al. [85] reported improvement in myocardial contractibility when autologous MSCs were transplanted with endothelial progenitor cells. Despite the fact that MSCs are proven to be effective in MI and related problems, still the ability of the heart to retain cells is low; only 10% cell retention after 4 h of cells injection and 1% after 24 h [86]. Roura et al. [87] recorded that UCB-MSCs proliferated and then differentiated into endothelial lineage, were retained for several weeks when injected in acute MI mice. Transplantation of UCB-MSCs into myocardial infarction animal model along with fibronectinimmobilized polycaprolactone nanofibers were found very effective [88].
