Stem Cell Theraby in Parasitic Diseases

Stem cell theraby for some parasitic diseases Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. They are found in multicellular organisms. In mammals, 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—ectoderm, endoderm and mesoderm but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues. There are three known accessible sources of autologous adult stem cells in humans: 1.

Bone marrow, which requires extraction by harvesting, that is,

drilling into bone (typically the femur or iliac crest). 2.

Adipose tissue (lipid cells), which requires extraction by

liposuction. 3.

Blood, which requires extraction through apheresis, wherein

blood is drawn from the donor (similar to a blood donation), and

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passed through a machine that extracts the stem cells and returns other portions of the blood to the donor. Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures. Adult stem cells are frequently used in medical therapies, for example in bone marrow transplantation. Stem cells can now beartificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through Somatic-cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies.

Properties The classical definition of a stem cell requires that it possess two properties: •

Self-renewal: the ability to go through numerous cycles of cell

division while maintaining the undifferentiated state. •

Potency: the capacity to differentiate into specialized cell types.

In the strictest sense, this requires stem cells to be either totipotent or pluripotent—to be able to give rise to any mature cell type, Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]

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•

Totipotent (a.k.a. omnipotent) stem cells can differentiate into

embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism.These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent. •

Pluripotent stem cells are the descendants of totipotent cells

and can differentiate into nearly all cells, i.e. cells derived from any of the three germ layers. •

Multipotent stem cells can differentiate into a number of cell

types, but only those of a closely related family of cells. •

Oligopotent stem cells can differentiate into only a few cell

types, such as lymphoid or myeloid stem cells. •

Unipotent cells can produce only one cell type, their own, but

have the property of self-renewal, which distinguishes them from non-stem cells (e.g. progenitor cells, muscle stem cells). The patients with parasitic infections, who usually belong to the lower socioeconomic strata of our society, have limited therapeutic options. Chemotherapy is virtually the first choice for the treatment of many parasitic infections. However, there is a worry about drug resistance following long-term, repeated implementation of mass drug administration. Stem cell therapy may help these patients. Stem cell therapy is an interventional treatment that introduces new cells into damaged tissues, which help in treating many diseases and injuries. It has been proved that stem cell therapy is effective for the treatment of cancers, diabetes mellitus, Parkinson's disease, 3

Huntington's disease, cardiovascular diseases, neurological disorders, and many other diseases. Recently, stem cell therapy has been introduced to treat parasitic infections. The culture supernatant of mesenchymal stem cells (MSCs) is found to inhibit activation and proliferation of macrophages induced by the soluble egg antigen of Schistosoma japonicum, and MSC treatment relieves S. japonicuminduced liver injury and fibrosis in mouse models. In addition, transplantation of MSCs into naïve mice is able to confer host resistance against malaria, and MSCs are reported to play an important role in host protective immune responses against malaria by modulating regulatory T cells. In mouse models of Chagas disease, bone marrow mononuclear cell has been shown effective in reducing inflammation and fibrosis in mice infected with Trypanosoma cruzi, and transplantation of the bone marrow mononuclear cells prevents and reverses the right ventricular dilatation induced by T. cruzi infection in mice. Preliminary clinical trials demonstrate that transplantation of bone marrow derived-cells may become an important therapeutic modality in the management of end-stage heart diseases associated with Chagas disease. Based on these exciting results, it is considered by stating that it is firmly believed that, within the next few years, we will be able to find the best animal models and the appropriate stem cell type, stem cell number, injection route, and disease state that will result in possible benefits for the patients with parasitic infections, and stem cell therapy, although at an initial stage currently, will become a real therapeutic 4

option for parasitic diseases. The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to John B. Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. Their surprising discov- eries have provided new tools for scientists around the world and led to remarkable progress in many areas of medicine. Actually, stem cell therapy has generated a huge amount of attention during the last two decades. Stem cell therapy is a kind of intervention strategy that introduces new cells into damaged tissues, which help in treating many diseases and injuries.

Stem cell therapy for schistosomiasis Schistosomiasis, caused by blood flukes (trematodes) of the genus Schistosoma, is an infectious disease affecting over 300 million people and leading to the loss of 1.53 million disability-adjusted life years in tropical and subtropical areas of the world. The major pathologic lesions of schistosomiasis are the hepatic granuloma formation around schistosome eggs at acute stage of the infection, followed by hepatic fibrosis at chronic and advanced stages. Currently, the treatment of this neglected tropical disease still depends on praziquantel, the drug of choice for human schistosomiases. However, the potential likelihood of emergence of praziquantel resistance urges the development of novel strategies for the treatment of Schistosoma japonicum infections

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Mesenchymal stem cells (MSCs), which have potential as seed cells, can be used for the treatment of various human diseases, including pathogenic infections. Considering the previous successes in therapy of infectious diseases and their antifibrotic effects, MSC therapy was introduced with the aim to evaluate the potential of MSCs for treating S. japonicum infections. It was observed that the RAW264.7 mouse macrophages be- came round, with significantly reduced sizes and less pseudo- podia following incubation in the MSC culture supernatant plus soluble egg antigen (SEA) of S. japonicum for 12 h, as compared to those cultured in SEA, SEA plus Dulbecco’s Modified Eagle Medium (DMEM), and SEA plus the culture supernatant of the rat renal tubule epithelial cell line NRK- 52E. The TNF -α mRNA levels in the macrophages cultured in the MSC culture supernatant plus SEA for 12 and 24 h were 1.0 ± 0.4 and 1.0 ± 0.5 times greater than those in negative controls, but they were significantly lower than those cultured in SEA plus NRK-52E cell culture supernatant and SEA plus DMEM (all P values