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Updated: Aug 14, 2026
Generation, Maintenance, and Characterization of Human Pluripotent Stem Cell-derived Intestinal and Colonic Organoids
Published on: July 9, 2021
Stem cells: the intestinal stem cell as a paradigm
S P Bach1, A G Renehan, C S Potten
1CRC Department of Epithelial Biology, Paterson Institute for Cancer Research and Department of Surgery, Christie Hospital NHS Trust, Wilmslow Road, Manchester, UK.
Abstract:
Stem cell research provides a foundation for therapeutic advancement in oncology, clinical genetics and a diverse array of degenerative disorders. For example, the elucidation of pathways governing proliferative regulation and differentiation within cellular systems will result in medical strategies aimed at the root cause of cancer. At present the characterization of reliable stem cell markers is the immediate aim in this particular field. Over the past 30 years investigators have determined many of the physical and functional properties of stem cells through careful and imaginative experimentation. Intestinal stem cells reside at the crypt base and give rise to all cell types found within the crypt. They readily undergo altruistic apoptosis in response to toxic stimuli although their progeny are hardier and will regain stem cell function to repopulate the tissue compartment, giving rise to the concept of a proliferative hierarchy. Contention exists when deciding whether the full complement of cells within a crypt is derived from either a single or multiple stems. Evidence has also arisen to challenge the long held view that colorectal tumours arise from a single mutated stem cell, as early adenomas from a human XO/XY mosaic contained distinct clones. Mechanisms governing the stem cell cycle and subsequent proliferative activity largely remain obscure. The adenomatous polyposis coli gene product has, however, been shown to promote the degradation of beta-catenin, an enhancer of cell proliferation, thereby downregulating this activity in healthy individuals.
Insights
Stem cell research is key to advancing treatments for cancer and degenerative diseases. Understanding stem cell markers and their role in tissue repair and tumor development is crucial for future therapies.
Area of Science:
- * Stem cell biology
- * Cancer research
- * Regenerative medicine
Background:
- * Stem cell research is foundational for therapeutic advancements in oncology, clinical genetics, and degenerative disorders.
- * Identifying reliable stem cell markers is an immediate goal for understanding cellular systems and developing targeted medical strategies.
- * Stem cells exhibit properties like altruistic apoptosis and the ability to repopulate tissues, forming a proliferative hierarchy.
Purpose of the Study:
- * To explore the role of stem cells in tissue regeneration and disease, particularly cancer.
- * To investigate the mechanisms governing stem cell proliferation and differentiation.
- * To challenge existing paradigms regarding tumor development and stem cell origins.
Main Methods:
- * Review of experimental findings on stem cell properties over the past 30 years.
- * Examination of intestinal stem cell behavior in crypts and response to toxic stimuli.
- * Analysis of evidence challenging the single mutated stem cell theory for colorectal tumors.
Main Results:
- * Stem cells at the crypt base differentiate into all cell types within the crypt.
- * Progeny of stem cells can regain function to repopulate tissues, illustrating a proliferative hierarchy.
- * Evidence suggests colorectal tumors may arise from multiple clones, not a single mutated stem cell.
Conclusions:
- * Elucidating stem cell pathways is vital for developing effective cancer and degenerative disorder treatments.
- * Further research is needed to understand the obscure mechanisms of stem cell cycle and proliferation.
- * The adenomatous polyposis coli gene product's role in downregulating beta-catenin highlights a mechanism in healthy individuals.
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