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

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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.

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Abbreviations

PN:

Parenteral nutrition

ISCs:

Intestinal stem cells

SCT:

Stem cell-based therapy

TE:

Tissue engineering

CBCs:

Crypt base columnar cells

DCAMKL1:

Doublecortin and Ca2+/calmodulin-dependent kinase-like 1

LRCs:

Label-retaining cells

Lgr5:

Leucin-rich repeat-containing G-protein-coupled receptor 5

mTert:

Mouse telomerase reverse transcriptase

Fz:

7-Transmembrane Frizzled

LRP:

Single-span transmembrane protein

APC:

Adenomatous polyposis coli

CKI:

Axin displace β-catenin allowing casein kinaseI

GSK3 β:

Glycogen synthase kinase3 β

PP2A:

Protein phosphatase

IBD:

Inflammatory bowel disease

NEC:

Necrotizing enterocolitis

SBS:

Short bowel syndrome

MSCs:

Mesenchymal stem cells

OU:

Organoid units

TESI:

Tissue-engineered small intestine

EGF:

Epidermal growth factor

TrCP:

Transducin repeat-containing protein

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Acknowledgments

This work was supported by National Science Council, Taiwan (101-2221-E-155-044-MY3).

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The authors declare no competing interests in relation to this manuscript.

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Authors and Affiliations

  1. Graduate School of Biotechnology and Bioengineering, Yuan Ze University, Chung-Li City, Taoyuan, Taiwan

    Mahmoud Shaaban Mohamed

  2. Department of Chemical Engineering and Materials Science, Yuan Ze University, No. 135, Yuan-Tung Road, Chung-Li City, 32003, Taoyuan, Taiwan

    Yun Chen & Chao-Ling Yao

  3. Department of Surgery, Far Eastern Memorial Hospital, Pan-Chiao, New Taipei, Taiwan

    Yun Chen

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  1. Mahmoud Shaaban Mohamed
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Correspondence to Chao-Ling Yao.

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Mahmoud Shaaban Mohamed and Yun Chen have contributed equally to this work.

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Mohamed, M.S., Chen, Y. & Yao, CL. Intestinal stem cells and stem cell-based therapy for intestinal diseases. Cytotechnology 67, 177–189 (2015). https://doi.org/10.1007/s10616-014-9753-9

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