الفهرس 
Adult Stem Cells ASCs)Only 14 pages are availabe for public view
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Abstract
Gastrointestinal disorders such as inflammatory bowel disease (IBD), Celiac disease, necrotizing enterocolitis (NEC) and Hirschsprung disease (HSCR) are concerning sources of patient morbidity and mortality within the pediatric community. Medical management of these diseases is often suboptimal, and surgical resection of the diseased intestine may be warranted. In many cases, however, surgical resection leaves the patient with an inadequate length of small intestine that precludes normal nutrient and fluid absorption. These patients may therefore suffer short bowel syndrome (SBS) and require long term parenteral nutritional support.
So, studies continue with the hopes of finding means to replace or supplement the absorptive properties of the native intestine. In this regard, stem cell therapy represents a novel treatment modality with increasing therapeutic potential. This new therapy based on stem cell transplantation or endogenous stem cells. Haematopoietic stem cell transplantation is the oldest stem cell therapy and is the treatment that is most widely available.
Stem cells are one of most fascinating areas of biology today and the recent progress in this promising area has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human.
Stem cells have two important characters that distinguish them from other types of cells. First, they are unspecialized or undifferentiated precursor cells with the capacity to renew themselves for long periods through cell division. The second is under certain physiological or experimental conditions, they can be induced to differentiate to become cells with special functions such as functional epithelial cells of gastrointestinal mucosa and neurons and glial cells of enteric nervous system.
In this literature we focused on the sources of the stem cells that may be applicable to the treatment of pediatric gastrointestinal disorders and how to isolate and purify it. In addition, we reviewed some pediatric gastrointestinal disorders where stem cells and tissue engineering show promise and reviewed the studies suggesting that stem cells may work for these conditions.
Stem cells can be derived from embryonic, fetal, neonatal, and adult tissues. Each has advantages and disadvantages regarding potential use for cell based regenerative therapies. As they differ in the number and types of differentiated cells types that they can become. Embryonic stem cells are pluripotent and can become all cell types of the body, whilst the other types of stem cells are generally limited to be differentiated into different specialized cells.
The identification of a rare population of multipotent stem cells of the gastrointestinal tract which are localized within the niches in the intestinal crypts and gastric glands in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering.
In addition, differentiated somatic adult cells can be epigenetically reprogrammed to produce pluripotent stem cells that would be isogenic to the donor individual and could be used as delivery system for expressing the therapeutic molecules in specific damaged areas of different tissues.
There are several studies that have been shown tremendous potential exists in the treatment of gastrointestinal disorders, such as IBD, Celiac disease, NEC, HSCR and SBS with stem cells and give hopes to treat or even cure them.
Stem cell therapy has recently been found to benefit patients suffering from IBD. As positive effects were noted in several studies which examined IBD patients undergoing allogenic stem cell transplantation usually for hematological diseases. Also, a remission of IBD has been reported after autologus stem cell transplantation for different pathologies. A potential mechanism of action is the elimination of immunological active cell populations. Moreover, cellular therapy for the treatment of inflammatory bowel diseases has already been initiated, and has been met with modest success.
In a recent published trial, the applicability of autologous stem cells transplantation in a selected group of refractory coeliacs with aberrant T cells was tested. On follow up, the patients showed improvement in the small intestinal histology, together with impressive clinical improvement and normalization of hematologic and biochemical markers with no major non-hematologic toxicity or transplantation-related mortality observed. These preliminary results showed that high-dose chemotherapy followed by autologous HSCs transplantation seems feasible and safe and might result in long-term improvement of patients with RCD type II.
Stem cell therapy for the treatment of necrotizing enterocolitis has not yet been addressed. But, there are published medical peer reviewed literatures supports that stem cell therapy could be a future potential option for the treatment of ischemic and inflammatory gut diseases. Particularly, necrotizing enterocolitis a condition that might benefit of cell therapy, given its ischemic and inflammatory nature.
Although it had long been believed that the CNS in mammals is incapable of regenerating after birth, adult neurogenesis is now well established, including in humans. So, stem cell therapy has engendered some enthusiasm as a potential treatment for HSCR. There are several studies have been shown that function of the aganglionic bowel might be restored by neurons that differentiate from autologous or heterologous neural stem cells. These neural stem cells can be generated from embryologic or postnatal gut.
Intestinal tissue engineering studies, which are an attractive therapeutic alternative to intestinal transplantation avoiding its risks, to counter SBS have already been initiated, and have been met with modest success. The principal of tissue engineering involves using a scaffold that provides both the initial mechanical structure and template for the engineered tissue. Cells are seeded onto the scaffold, which organize into the desired tissue either before or after implantation. The scaffold may be a permanent implant or tailored to degrade after extracellular matrix has been deposited and the tissue has become mechanically self-supporting. The cells should possess the ability to differentiate into all aspects of the intestine, including absorptive and secretory cells, as well as cells to supply the nearby vasculature and physical support. In this regard, stem cells, with their multilineage capabilities, are probably most ideal to differentiate into all the necessary cells of the bowel.
Therefore, Although Stem cell research has made tremendous advancements over the past decade through multiple studies, and it has become clear that stem cells possess tremendous therapeutic potential. Stem cell therapy has not yet been adopted for routine use in the treatment of pediatric gastrointestinal disorders. But, a few disorders, such as IBD, Celiac disease, NEC, HSCR and SBS, may be amenable to stem cell therapy, and the application of stem cell therapies for these disorders require further insight into the mechanisms of stem cells which may provide better ways of utilizing progenitor cell therapy for maximizing therapeutic potential during the treatment.