Intestinal stem cells and stem cell-based therapy for intestinal diseases

Abstract

Currently, many gastrointestinal diseases are a major reason for the increased mortality rate of children and adults every year. Additionally, these patients may cope with the high cost of the parenteral nutrition (PN), which aids in the long-term survival of the patients. Other treatment options include surgical lengthening, which is not sufficient in many cases, and intestinal transplantation. However, intestinal transplantation is still accompanied by many challenges, including immune rejection and donor availability, which may limit the transplant's success. The development of more safe and promising alternative treatments for intestinal diseases is still ongoing. Stem cell-based therapy (SCT) and tissue engineering (TE) appear to be the next promising choices for the regeneration of the damaged intestine. However, suitable stem cell source is required for the SCT and TE process. Thus, in this review we discuss how intestinal stem cells (ISCs) are a promising cell source for small intestine diseases. We will also discuss the different markers were used to identify ISCs. Moreover, we discuss the dominant Wnt signaling pathway in the ISC niche and its involvement in some intestinal diseases. Additionally, we discuss ISC culture and expansion, which are critical to providing enough cells for SCT and TE. Finally, we conclude and recommend that ISC isolation, culture and expansion should be considered when SCT is a treatment option for intestinal disorders. Therefore, we believe that ISCs should be considered a cell source for SCT for many gastrointestinal diseases and should be highlighted in future clinical applications.

Long-term renewable human intestinal epithelial stem cells as monolayers: A potential for clinical use

“…Intestinal stem cell in vitro culturing has been used to study cellular mechanisms behind many pathologic states [31]. Intestinal diseases such as congenital tufting enteropathy, celiac disease, Crohn’s disease, or ulcerative colitis can potentially be treated with intestinal stem cell therapy [31, 32].…”

“…Intestinal diseases such as congenital tufting enteropathy, celiac disease, Crohn’s disease, or ulcerative colitis can potentially be treated with intestinal stem cell therapy [31, 32]. Stem cells and stem cell derived organoids can be transfected with specific vectors and transplanted into patients with known mutations, achieving integration of proper genetic material [31, 32]. …”

Distinct Effects of Growth Hormone and Glutamine on Activation of Intestinal Stem Cells

“…The function and activity of ISCs can be studied in vitro or in vivo. Recently, isolation of the ISC‐containing crypt fraction and observation of organoid formation in an in vitro culture system have also been used for studies of intestinal biophysiology, pathology, and regeneration …”

Stem cell therapy in inflammatory bowel disease: A promising therapeutic strategy?

“…These organoids will be an important way to reach a more personalized medicine for IBD. These results highlight that those intestinal stem cells are a very promising source of stem cells for future patient-specific regeneration of the digestive tract [68] . …”

“…ISCs have proliferation and mutipotency capabilities, i.e., they are able to divide and later differentiate into all intestinal subtypes (enterocytes, globet cells, Paneth cells and neuroendocrine cells). Recently, research in the ISCs field has advanced greatly and many ISCs markers have been identified [68] . However, an exhaustive characterization of ISCs as well as the identification of specific markers still remains elusive [64] .…”