Understanding the Biology of Human Interstitial Cells of Cajal in Gastrointestinal Motility

Foong, Daphne; Zhou, Jerry; Zarrouk, Ali; Ho, Vincent; O’Connor, Michael D.

doi:10.3390/ijms21124540

Cited by 127Gastrointestinal motility and disordersCongenital gastrointestinal and neural anomaliesGastrointestinal Tumor Research and Treatment

Understanding the Biology of Human Interstitial Cells of Cajal in Gastrointestinal Motility

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Foong, Daphne, Zhou, Jerry, Zarrouk, Ali, Ho, Vincent, O’Connor, Michael D.·2020·International Journal of Molecular Sciences

DOI 10.3390/ijms21124540PMC PMC7352366

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Abstract

Millions of patients worldwide suffer from gastrointestinal (GI) motility disorders such as gastroparesis. These disorders typically include debilitating symptoms, such as chronic nausea and vomiting. As no cures are currently available, clinical care is limited to symptom management, while the underlying causes of impaired GI motility remain unaddressed. The efficient movement of contents through the GI tract is facilitated by peristalsis. These rhythmic slow waves of GI muscle contraction are mediated by several cell types, including smooth muscle cells, enteric neurons, telocytes, and specialised gut pacemaker cells called interstitial cells of Cajal (ICC). As ICC dysfunction or loss has been implicated in several GI motility disorders, ICC represent a potentially valuable therapeutic target. Due to their availability, murine ICC have been extensively studied at the molecular level using both normal and diseased GI tissue. In contrast, relatively little is known about the biology of human ICC or their involvement in GI disease pathogenesis. Here, we demonstrate human gastric tissue as a source of primary human cells with ICC phenotype. Further characterisation of these cells will provide new insights into human GI biology, with the potential for developing novel therapies to address the fundamental causes of GI dysmotility.

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Interstitial cells of Cajal (ICCs) act as gastrointestinal pacemakers, coordinating the rhythmic contractions necessary for the transit of gastric contents.
“These cells act as gastrointestinal pacemakers, coordinating the rhythmic contractions necessary for the transit of gastric contents [50, 51].”
From Diabetic gastroparesis: pathophysiology and impact on insulin timing choices (2026) · cites this paper as [50]

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Lee, H., Hennig, G. W., Fleming, N., Keef, K. D., Spencer, N. J., Ward, S. M., Sanders, K. M., & Smith, T. K. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.06.024 · Cited by 60 · see citing works
Regional Distribution of Interstitial Cells of Cajal (ICC) in Human Stomach
Yun, H. Y., Sung, R., Kim, Y. C., Choi, W., Kim, H. S., Kim, H., Lee, G. J., You, R. Y., Park, S.-M., Yun, S. J., et al. (2010) · Korean Journal of Physiology and Pharmacology · doi:10.4196/kjpp.2010.14.5.317 · Cited by 58 · see citing works
Gastrointestinal Motility Disorders: An Update
Lacy, B. E., & Weiser, K. (2006) · Digestive Diseases · doi:10.1159/000092876 · Cited by 57 · see citing works
Diabetic Gastroparesis: Functional/Morphologic Background, Diagnosis, and Treatment Options
Horváth, V. J., Izbéki, F., Lengyel, C., Kempler, P., & Várkonyi, T. T. (2014) · Current Diabetes Reports · doi:10.1007/s11892-014-0527-8 · Cited by 56 · see citing works
Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gastroparesis
Grover, M., Gibbons, S. J., Nair, A., Bernard, C. E., Zubair, A. S., Eisenman, S. T., Wilson, L., Miriel, L. A., Pasricha, P. J., Parkman, H. P., et al. (2018) · BMC Medical Genomics · doi:10.1186/s12920-018-0379-1 · Cited by 54 · see citing works
Immunoreactivity for Ano1 Detects Depletion of Kit-positive Interstitial Cells of Cajal in Patients with Slow Transit Constipation
Kashyap, P., Gomez-Pinilla, P. J., Pozo, M. J., Cima, R., Dozois, E., Larson, D., Ordog, T., Gibbons, S., & Farrugia, G. (2011) · Neurogastroenterology and Motility · doi:10.1111/j.1365-2982.2011.01729.x · Cited by 54 · see citing works
A mouse model of a human multiple GIST family with KIT‐Asp820Tyr mutation generated by a knock‐in strategy
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Is Interstitial Cells of Cajal‒opathy Present in Gastroparesis?
Bashashati, M., & McCallum, R. W. (2015) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm15075 · Cited by 50 · see citing works
Aging-dependent decrease in the numbers of enteric neurons, interstitial cells of Cajal and expression of connexin43 in various regions of gastrointestinal tract
Sun, T., Li, D., Hu, S., Huang, L., Sun, H., Yang, S., Wu, B., Ji, F., & Zhou, D. (2018) · Aging · doi:10.18632/aging.101677 · Cited by 50 · see citing works
Interstitial cells of Cajal and telocytes in the gut: twins, related or simply neighbor cells?
Vannucchi, M. G., & Traini, C. (2016) · BioMolecular Concepts · doi:10.1515/bmc-2015-0034 · Cited by 48 · see citing works
Proteomics in gastroparesis: unique and overlapping protein signatures in diabetic and idiopathic gastroparesis
Grover, M., Dasari, S., Bernard, C. E., Chikkamenahalli, L. L., Yates, K. P., Pasricha, P. J., Sarosiek, I., McCallum, R. W., Koch, K. L., Abell, T. L., et al. (2019) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00115.2019 · Cited by 42 · see citing works
Characterization of smooth muscle, enteric nerve, interstitial cells of Cajal, and fibroblast-like cells in the gastric musculature of patients with diabetes mellitus
Park, K. S., Cho, K. B., Hwang, I. S., Park, J. H., Jang, B. I., Kim, K. O., Jeon, S. W., Kim, E. S., Park, C. S., & Kwon, J. G. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i46.10131 · Cited by 38 · see citing works
Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression
Tang, C.-M., Lee, T. E., Syed, S. A., Burgoyne, A. M., Leonard, S. Y., Gao, F., Chan, J. C., Shi, E., Chmielecki, J., Morosini, D., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.12909 · Cited by 35 · see citing works
Interstitital cells of Cajal in the human stomach: distribution and relationship with enteric innervation.
Manneschi, L. I., Pacini, S., Corsani, L., Bechi, P., & Ms, F.-P. (2004) · PubMed · doi:10.14670/hh-19.1153 · Cited by 34 · see citing works
Purification of interstitial cells of Cajal by fluorescence-activated cell sorting
Ördög, T., Redelman, D. D., Miller, L. J., Horváth, V. J., Zhong, Q., Almeida-Porada, G. D., Zanjani, E. D., Horowitz, B., & Sanders, K. M. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00273.2003 · Cited by 32 · see citing works
Quantitative analysis by flow cytometry of interstitial cells of Cajal, pacemakers, and mediators of neurotransmission in the gastrointestinal tract
Ördög, T., Redelman, D. D., Horváth, V. J., Miller, L. J., Horowitz, B., & Sanders, K. M. (2004) · Cytometry Part A · doi:10.1002/cyto.a.20078 · Cited by 31 · see citing works
Interleukin 10 Restores Gastric Emptying, Electrical Activity, and Interstitial Cells of Cajal Networks in Diabetic Mice
Choi, K. M., Gibbons, S., Sha, L., Beyder, A., Verhulst, P.-J., Cipriani, G., Phillips, J. E., Bauer, A., Ordog, T., Camp, J., et al. (2016) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2016.04.006 · Cited by 31 · see citing works
Bioengineered intestinal muscularis complexes with long-term spontaneous and periodic contractions
Wang, Q., Wang, K., Solórzano-Vargas, R. S., Lin, P., Walthers, C. M., Thomas, A.-L. A., Martı́n, M. G., & Dunn, J. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195315 · Cited by 30 · see citing works
Smooth Muscle Transcriptome Browser: offering genome-wide references and expression profiles of transcripts expressed in intestinal SMC, ICC, and PDGFRα+ cells
Breland, A. E., Ha, S. E., Jorgensen, B. G., Jin, B., Gardner, T. A., Sanders, K. M., & Ro, S. (2019) · Scientific Reports · doi:10.1038/s41598-018-36607-6 · Cited by 27 · see citing works
Interstitial cells of Cajal in the gastrointestinal musculature of Wjic c-kit mutant mice
Iino, S., Horiguchi, S., & Horiguchi, K. (2011) · Journal of Smooth Muscle Research · doi:10.1540/jsmr.47.111 · Cited by 23 · see citing works
The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy
Zhou, J., O’Connor, M. D., & Ho, V. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102059 · Cited by 22 · see citing works
Self-citation
Immunomagnetic enrichment of interstitial cells of Cajal
Ördög, T., Redelman, D. D., Horowitz, N. N., & Sanders, K. M. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00281.2003 · Cited by 22 · see citing works
Delivery of Mesenchymal Stem Cells from Gelatin–Alginate Hydrogels to Stomach Lumen for Treatment of Gastroparesis
Joddar, B., Tasnim, N., Thakur, V., Kumar, A., McCallum, R. W., & Chattopadhyay, M. (2018) · Bioengineering · doi:10.3390/bioengineering5010012 · Cited by 22 · see citing works
Bioengineering functional smooth muscle with spontaneous rhythmic contraction in vitro
Kobayashi, M., Khalil, H. A., Lei, N., Wang, Q., Wang, K., Wu, B. M., & Dunn, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-31992-4 · Cited by 21 · see citing works
Characterization of Interstitial Cajal Progenitors Cells and Their Changes in Hirschsprung’s Disease
Chen, Z.-H., Zhang, Y., Jiang, W., Yang, C., Zou, G.-M., Kong, Y., & Cai, W. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086100 · Cited by 20 · see citing works
Restoration of gut motility in Kit-deficient mice by bone marrow transplantation
Ishii, S., Tsuji, S., Tsujii, M., Nishida, T., Watabe, K., Iijima, H., Takehara, T., Kawano, S., & Hayashi, N. (2009) · Journal of Gastroenterology · doi:10.1007/s00535-009-0077-z · Cited by 20 · see citing works
Establishment of pacemaker activity in tissues allotransplanted with interstitial cells of C ajal
McCann, C. J., Hwang, S. J., Bayguinov, Y. R., Colletti, E. J., Sanders, K. M., & Ward, S. M. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12140 · Cited by 20 · see citing works
Use of anoctamin 1 (ANO1) to evaluate interstitial cells of Cajal in Hirschsprung’s disease
Coyle, D., Kelly, D., O’Donnell, A. M., Gillick, J., & Puri, P. S. (2015) · Pediatric Surgery International · doi:10.1007/s00383-015-3822-9 · Cited by 19 · see citing works
Visualization of the Interstitial Cells of Cajal (ICC) Network in Mice
Chen, Y., Shamu, T., Chen, H., Besmer, P., Sawyers, C. L., & Chi, P. (2011) · Journal of Visualized Experiments · doi:10.3791/2802 · Cited by 17 · see citing works
Bone Marrow Derivation of Interstitial Cells of Cajal in Small Intestine Following Intestinal Injury
Liu, D., Wang, F., Zou, Z., Shiwu, D., Wang, J., Ran, X., Li, C., Shi, C., & Su, Y. (2010) · BioMed Research International · doi:10.1155/2010/164986 · Cited by 15 · see citing works
Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis
Herring, B. P., Chen, M., Mihaylov, P. V., Hoggatt, A. M., Gupta, A., Nakeeb, A., Choi, J. N., & Wo, J. M. (2019) · BMC Medical Genomics · doi:10.1186/s12920-019-0550-3 · Cited by 13 · see citing works
Bone Marrow Derived Kit-positive Cells Colonize the Gut but Fail to Restore Pacemaker Function in Intestines Lacking Interstitial Cells of Cajal
McCann, C. J., Hwang, S. J., Hennig, G. W., Ward, S. M., & Sanders, K. M. (2014) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm14026 · Cited by 9 · see citing works
Interstitial cell network volume is reduced in the terminal bowel of ageing mice
Gamage, P. P. K. M., Patel, B. A., Yeoman, M. S., Ranson, R. N., & Saffrey, M. J. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13794 · Cited by 7 · see citing works
Is there a Role for Human Pluripotent Stem Cells in Modelling Interstitial Cells of Cajal and Gut Motility Disorders?
Meng, W., Zhou, J., Elliott, R., Murphy, P., Ho, V., & O’Connor, M. D. (2014) · Current Stem Cell Research & Therapy · doi:10.2174/1574888x09666141112120040 · Cited by 6 · see citing works
Self-citation
Long-Term Repopulation Effects of Donor BMDCs on Intestinal Epithelium
Dengqun, L., Fengchao, W., Zou, Z., Shiwu, D., Chunmeng, S., Junping, W., Xinze, R., & Su, Y. (2009) · Digestive Diseases and Sciences · doi:10.1007/s10620-009-0991-1 · Cited by 6 · see citing works

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[35]Komuro T. Comparative morphology of interstitial cells of Cajal: Ultrastructural characterization Microsc. Res. Tech. 1999 47 267 285 10.1002/(SICI)1097-0029(19991115)47:4<267::AID-JEMT5>3.0.CO;2-O 10602287 · DOI

Sorted by citations

Overabundance of Veillonella parvula promotes intestinal inflammation by activating macrophages via LPS-TLR4 pathway
Zhan, Z., Liu, W., Pan, L., Bao, Y., Yan, Z., & Li, H. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01015-3 · Cited by 105 · see citing works
“Interstitial cells of Cajal (ICCs) are pacemaker cells that promote intestinal motility [14].”
Background
Simulating human gastrointestinal motility in dynamic in vitro models
Li, Y. H., & Kong, F. (2022) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.13007 · Cited by 78 · see citing works
NF‐κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation
Zamanian, M., Alsaab, H., Golmohammadi, M., Yumashev, A., Jabba, A. M., Abid, M. K., Joshi, A., Alawadi, A., Jafer, N. S., Kianifar, F., et al. (2024) · Cell Biochemistry and Function · doi:10.1002/cbf.4030 · Cited by 81 · see citing works
“202 They generate and propagate electrical slow waves, which are crucial for rhythmic contractions and the movement of food through the digestive tract.”
Background
Notoginsenoside R1 promotes Lgr5+ stem cell and epithelium renovation in colitis mice via activating Wnt/β-Catenin signaling
Yu, Z., Gao, R., Lv, C., Geng, X., Ren, Y., Zhang, J., Ren, J., Wang, H., Ai, F., Wang, Z.-Y., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01250-7 · Cited by 60 · see citing works
“However, disruptions in the process of ISC proliferation and differentiation can impede the coordinated restoration of damaged intestinal tissues, leading to signi ﬁ cant barrier defects [10].”
Background
Nitric Oxide: From Gastric Motility to Gastric Dysmotility
Idrizaj, E., Traini, C., Vannucchi, M. G., & Baccari, M. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22189990 · Cited by 58 · see citing works
Campylobacter jejuni virulence factors: update on emerging issues and trends
Tikhomirova, A., McNabb, E. R., Petterlin, L., Bellamy, G. L., Lin, K. H., Santoso, C. A., Daye, E. S., Alhaddad, F. M., Lee, K. P., & Roujeinikova, A. (2024) · Journal of Biomedical Science · doi:10.1186/s12929-024-01033-6 · Cited by 54 · see citing works
“…and cleared of CdtB-positive C. jejuni , rats continued to show IBS-like symptoms, including chronic altered bowel pattern, rectal inflammation and reduced deep muscular plexus interstitial cells of Cajal (ICC-DMP) - “intestinal pacemakers” that are required for normal intestinal motility [163].”
Background
Ameliorating effects of transcutaneous auricular vagus nerve stimulation on a mouse model of constipation-predominant irritable bowel syndrome
Liu, J., Dai, Q., Qu, T., Ma, J., Lv, C., Wang, H., & Yu, Y. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106440 · Cited by 53 · see citing works
“ICC dysfunction or loss has been implicated in several gastrointestinal (GI) motility disorders such as gastroparesis, intestinal obstruction, and constipation (Foong et al., 2020).”
Background
Review article: Functional dyspepsia—a gastric disorder, a duodenal disorder or a combination of both?
Broeders, B., Carbone, F., Balsiger, L. M., Schol, J., Raymenants, K., Huang, I., Verheyden, A., Vanuytsel, T., & Tack, J. F. (2023) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17414 · Cited by 38 · see citing works
The role of mechanosensitive ion channels in the gastrointestinal tract
Yang, H., Hou, C., Xiao, W., & Qiu, Y. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.904203 · Cited by 35 · see citing works
“SpanishNobel Laureate physician Santiago Ramon y Cajal first described cells that are located between SMCs and the nerve endings in the GI tract (Foong et al., 2020).”
Background
Banxia Xiexin decoction: A review on phytochemical, pharmacological, clinical and pharmacokinetic investigations
Zhou, Z., An, R., You, L., Liang, K., & Wang, X. (2023) · Medicine · doi:10.1097/md.0000000000034891 · Cited by 30 · see citing works
“[75] Furthermore, recent studies have shown that interstitial cells of Cajal (ICCs) are gastrointestinal pacing cells, and the changes in their structure and number may be an important cause of gastrointestinal motility disorders.[103] As a specific marker of ICCs, stem cell factor (SCF) plays a crucial role in the gr…”
Result
Recent advances in understanding the roles of the enteric nervous system
Chanpong, A., Borrelli, O., & Thapar, N. (2022) · Faculty Reviews · doi:10.12703/r/11-7 · Cited by 27 · see citing works
Tissue engineering of the gastrointestinal tract: the historic path to translation
Collier, C. A., Mendiondo, C., & Raghavan, S. A. (2022) · Journal of Biological Engineering · doi:10.1186/s13036-022-00289-6 · Cited by 27 · see citing works
“SMCs and enteric neurons are also in close proximity to interstitial cells of Cajal (ICCs), which act as the “pacemakers of the gut” [47].”
Background
Advancements in Esophageal Stricture Treatment: The Role of Stents in Benign and Malignant Conditions
Noor, H., Sabău, D., Coțe, A., Mihetiu, A. F., Pirvut, V., Mălinescu, B., & Bratu, D. G. (2024) · Journal of Medical Sciences and Interdisciplinary Research · doi:10.51847/ltuxazrl0m · Cited by 25 · see citing works
Gut dysmotility in children with neurological impairment: the nutritional management
Corsello, A., Scatigno, L., Govoni, A., Zuccotti, G., Gottrand, F., Romano, C., & Verduci, E. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1200101 · Cited by 23 · see citing works
“Abnormalities in ICC number and structure have also been associated with other GI motility disorders such as gastroparesis (91, 92).”
Background
Effects of dietary fibre on enteral feeding intolerance and clinical outcomes in critically ill patients: A meta-analysis
Liu, T., Feng, P., Wang, C., Ojo, O., Wang, Y., & Wang, X. (2022) · Intensive and Critical Care Nursing · doi:10.1016/j.iccn.2022.103326 · Cited by 22 · see citing works
Therapeutic role of Wuda granule in gastrointestinal motility disorder through promoting gastrointestinal motility and decreasing inflammatory level
Jiang, Z. D., Zou, Q., Chen, Q., Zhang, J., Tang, H., Chen, J., Qin, Y., Yang, L., Chen, Z., & Cao, L. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1237686 · Cited by 20 · see citing works
“Especially for the majority of patients undergoing gastrointestinal surgery, GMD may directly lead to bowel failure (Foong et al., 2020).”
Background
Nobiletin, an active component of Wenyang Yiqi formula, alleviates constipation associated depression through targeting MAPT to inhibit the MAPK signaling pathway
Zhou, Q., He, Z., Yan, S., Wang, X., & Wu, B. (2023) · Phytomedicine · doi:10.1016/j.phymed.2023.155203 · Cited by 19 · see citing works
Biomaterials for inflammatory bowel disease: treatment, diagnosis and organoids
Wang, J., Shi, Y., Mao, B., Zhang, B., Yang, J., Hu, Z., & Liao, W. (2024) · Applied Materials Today · doi:10.1016/j.apmt.2024.102078 · Cited by 19 · see citing works
Telocytes and Other Interstitial Cells: From Structure to Function
Creţoiu, S. M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105271 · Cited by 18 · see citing works
“The importance of interstitial cells of Cajal is also debated in many gastrointestinal motility disorders, and the main issue is that most studies were carried out on animal models, and one needs to elucidate if the findings can be extended to humans [3].”
BackgroundInfluential
Identification of evodiamine and rutecarpine as novel TMEM16A inhibitors and their inhibitory effects on peristalsis in isolated Guinea-pig ileum
Zhao, Z., Xue, Y., Zhang, G., Jia, J., Xiu, R., Jia, Y., Wang, Y., Wang, X.-C., Li, H., Chen, P., et al. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174340 · Cited by 17 · see citing works
Studies of ultrastructure, gene expression, and marker analysis reveal that mouse bladder PDGFRA+ interstitial cells are fibroblasts
Clayton, D. R., Ruiz, W. G., Dalghi, M. G., Montalbetti, N., Carattino, M. D., & Apodaca, G. L. (2022) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00135.2022 · Cited by 17 · see citing works
Comprehensive landscape-style investigation of the molecular mechanism of acupuncture at ST36 single acupoint on different systemic diseases
Fan, X., Liu, Y., Li, S., Yang, Y., Zhao, Y., Li, W., Hao, J., Xu, Z., Zhang, B., Liu, W., et al. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26270 · Cited by 17 · see citing works
The importance of food quality, gut motility, and microbiome in SIBO development and treatment
Knez, E., Kadac-Czapska, K., & Grembecka, M. (2024) · Nutrition · doi:10.1016/j.nut.2024.112464 · Cited by 20 · see citing works
Telocytes’ Role in Modulating Gut Motility Function and Development: Medical Hypotheses and Literature Review
Banciu, D. D., Crețoiu, D., Creţoiu, S. M., Banciu, A., Popa, D., David, R., Berghea-Neamtu, C. S., Cipăian, C. R., Negrea, M. O., Gheonea, M., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137017 · Cited by 16 · see citing works
Intestinal microbiota: a new perspective on delaying aging?
Zhang, Y., Wang, X., Li, W., Yang, Y., Wu, Z., Lyu, Y., & Yue, C. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1268142 · Cited by 20 · see citing works
Contribution of Interstitial Cells of Cajal to Gastrointestinal Stromal Tumor Risk
Wang, Q., Huang, Z., Zhu, Y., Fu, F., & Lin, T. (2021) · Medical Science Monitor · doi:10.12659/msm.929575 · Cited by 16 · see citing works
“Reduction, injury, or loss of function of gastrointestinal tract ICCs may be associated with impaired gastrointestinal motility [20].”
Background
The Autonomic Nervous System in Acupuncture for Gastrointestinal Dysmotility: From Anatomical Insights to Clinical Medicine
Yang, N., Xie, X., Yan, W., Liu, Y.-D., Wang, H.-X., Yang, L.-X., & Liu, C. (2025) · International Journal of Medical Sciences · doi:10.7150/ijms.107643 · Cited by 15 · see citing works
“Gastrointestinal dysmotility originate throughout the entire length of the gut, from the esophagus to the colon, and are characterized by symptoms such as early satiation, nausea, vomiting, abdominal pain, bloating, and other [11].”
The regulatory effects of fucoidan and laminarin on functional dyspepsia mice induced by loperamide
Liu, T., Zhang, M., Asif, I. M., Wu, Y., Li, B., & Wang, L. (2023) · Food & Function · doi:10.1039/d3fo00936j · Cited by 15 · see citing works
New Role of the Serotonin as a Biomarker of Gut–Brain Interaction
Liu, H. N., Nakamura, M., & Kawashima, H. (2024) · Life · doi:10.3390/life14101280 · Cited by 15 · see citing works
The Key Ingredient Acacetin in Weishu Decoction Alleviates Gastrointestinal Motility Disorder Based on Network Pharmacology Analysis
Guo, X., Xu, Y., Hua-liang, T., Wang, X.-J., & Xiao, L. (2021) · Mediators of Inflammation · doi:10.1155/2021/5265444 · Cited by 15 · see citing works
“Millions of patients worldwide su ﬀ er from gastrointestinal motility disorders, which include debilitating symptoms such as chronic nausea and vomiting [3].”
Electroacupuncture at ST36 ameliorates gastric dysmotility in rats with diabetic gastroparesis via the nucleus tractus solitarius-vagal axis
Zhang, Y., Tang, Y., Zhou, J., Wei, Y., Peng, Y.-T., Yan, Z., & Yue, Z.-H. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i21.107395 · Cited by 16 · see citing works
“Beyond nNOS, ICCs dysfunction has been shown to be strongly associated with DGP. ICCs are essential for generating gastric slow waves and setting smooth muscle membrane potentials[21].”
Self-citation
Long non-coding RNA MEG3 promotes tumor necrosis factor-alpha induced oxidative stress and apoptosis in interstitial cells of cajal via targeting the microRNA-21 /I-kappa-B-kinase beta axis
Li, J., Bai, J., Tuerdi, N., & Liu, K. (2022) · Bioengineered · doi:10.1080/21655979.2022.2054501 · Cited by 14 · see citing works
Comparative effects of different enzymatic hydrolysates of konjac glucomannan on gut flora and constipation in rats
Chang, X., Liu, Y., Hu, M., Liu, Y., Jiang, C., Wang, Q., Jin, Q., Zhang, D., Yin, Z., & Zhang, J. (2022) · Food & Function · doi:10.1039/d2fo01144a · Cited by 15 · see citing works
Lactobacillus rhamnosus LRa05 Alleviates Constipation via Triaxial Modulation of Gut Motility, Microbiota Dynamics, and SCFA Metabolism
Zhang, J., Li, Q., Liu, S., Wang, N., Song, Y., Wu, T., & Zhang, M. (2025) · Foods · doi:10.3390/foods14132293 · Cited by 13 · see citing works
“The SCF/C-kit pathway imbalance impairs interstitial cells of Cajal (ICC), the intestinal “pacemakers”, slowing transit [6].”
Conceptualizing Epigenetics and the Environmental Landscape of Autism Spectrum Disorders
Torres, G., Mourad, M., Iqbal, S., Moses‐Fynn, E., Pandita, A., Siddhartha, S. S., Sood, R. A., Srinivasan, K., Subbaiah, R. T., Tiwari, A., et al. (2023) · Genes · doi:10.3390/genes14091734 · Cited by 13 · see citing works
Common Pathophysiological Mechanisms and Treatment of Diabetic Gastroparesis
Zhang, Y., Zhang, Y., Li, M., Tian, J., & Tong, X. (2024) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm23100 · Cited by 13 · see citing works
A comparative study of vestibular improvement and gastrointestinal effect of betahistine and gastrodin in mice
Zhang, Y.-X., Wang, H.-X., Li, Q.-X., Chen, A.-X., Wang, X., Zhou, S., Xie, S.-T., Li, H., Wang, J., Zhang, Q., et al. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.113344 · Cited by 13 · see citing works
Wei-Tong-Xin ameliorated cisplatin-induced mitophagy and apoptosis in gastric antral mucosa by activating the Nrf2/HO-1 pathway
Zhang, X., Wang, S., Jin, Y., Wang, J., Wang, R., Yang, X., Zhang, S., Yan, T., & Jia, Y. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116253 · Cited by 13 · see citing works
Tongbian decoction restores intestinal microbiota and activates 5-hydroxytryptamine signaling: implication in slow transit constipation
Li, H., Lv, N., Li, D., Qian, Y., Si, X., Hua, Y., Wang, Y., Han, X., & Xu, T. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1296163 · Cited by 12 · see citing works
“…immune factors, endocrine factors, laxatives, psychological factors, diet, and exercise habits have been implicated in the onset and exacerbation of STC (He et al., 2000; Lyford et al., 2002; Wedel et al., 2002; Foong et al., 2020; Serra et al., 2020; Wang H. et al., 2022; Kaji and Hori, 2023).”
Background
Bifidobacterium bifidum CCFM1163 alleviates cathartic colon by activating the BDNF-TrkB-PLC/IP 3 pathway to reconstruct the intestinal nerve and barrier
Zhu, S., Yu, Q., Xue, Y., Li, J., Huang, Y. C., Liu, W., Wang, G., Wang, L., Zhai, Q., Zhao, J., et al. (2025) · Food & Function · doi:10.1039/d4fo05835f · Cited by 12 · see citing works
Risk stratification of clinically relevant delayed gastric emptying after pancreaticoduodenectomy
Li, T., Qin, C., Zhao, B., Yang, X., Li, Z., Wang, Y., Guo, J., Han, X., Dai, M., & Wang, W. (2023) · BMC Surgery · doi:10.1186/s12893-023-02110-7 · Cited by 12 · see citing works
“…and hormonal disorders [2]; remnant stomach cannot generate effective basic electrical rhythm and contraction waves due to the lack of interstitial cells of Cajal (ICC) [10, 26, 27]; lack of migrating motor complexes (MMC) originating from the antrum and duodenum [28]; psychological factors [29].”
Background
Electroacupuncture Improves Intestinal Motility through Exosomal miR-34c-5p Targeting SCF/c-Kit Signaling Pathway in Slow Transit Constipation Model Rats
Kuang, H., Zhang, C.-S., Zhang, W., Cai, H., Yang, L., Yuan, N., Yuan, Y., Yang, Y., Zuo, C.-Y., & Zhong, F. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/8043841 · Cited by 10 · see citing works
“ICC is closely related to gastrointestinal motility and can emit pacemaker potential [8].”
Background
Effects of weaning on intestinal longitudinal muscle-myenteric plexus function in piglets
Li, J., Liu, F., Mo, K., Ni, H., & Yin, Y. (2023) · Science China Life Sciences · doi:10.1007/s11427-022-2391-x · Cited by 10 · see citing works
“Intestinal motility is regulated by the cooperation of different kinds of cells in the MP, such as enteric neurons, smooth muscle cells, enteric glial cells, and interstitial cells of Cajal (ICCs) (Foong et al., 2020).”
The traditional medicine bojungikki-tang increases intestinal motility
Kim, B., Kwon, H., Kim, J., Kwon, M., Lee, J. R., Kim, S. C., & Nam, J. (2021) · Pharmacognosy Magazine · doi:10.4103/pm.pm_507_20 · Cited by 10 · see citing works
Clinical applications and mechanisms of vagus nerve stimulation in the treatment of immune diseases: a review
Liu, J., Zheng, K., Dong, L., Lin, J., Zhang, C., Xie, Y., & Wang, Y. (2025) · International Journal of Surgery · doi:10.1097/js9.0000000000003160 · Cited by 11 · see citing works
“Cajal cells are key interstitial cells that regulate the electrophysiological activity of gastrointestinal smooth muscles [ 87 ] .”
Loureirin C extracted from Dracaena cochinchinensis S.C. Chen prevents rotaviral diarrhea in mice by inhibiting the intestinal Ca2+-activated Cl− channels
Guo, S., Yu, B., Jia, Q., Yan, H.-Y., Wang, L., Sun, F., Ma, T., & Yang, H. Y. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.117077 · Cited by 9 · see citing works
Glucose Stimulates Gut Motility in Fasted and Fed Conditions: Potential Involvement of a Nitric Oxide Pathway
Wemelle, E., Carneiro, L., Abot, A., Lésage, J., Cani, P. D., & Knauf, C. (2022) · Nutrients · doi:10.3390/nu14102176 · Cited by 10 · see citing works
Characteristics of the Cajal interstitial cells and intestinal microbiota in children with refractory constipation
Yuan, Y., Lü, Y., Zhang, Z., Cheng, W., Yan, K., Zheng, Y., Jin, Y., & Liu, Z. (2023) · Microbial Pathogenesis · doi:10.1016/j.micpath.2023.106373 · Cited by 8 · see citing works
Neuropathic Gastroduodenal Disorders Can Be Diagnosed by Non‐Invasive Body Surface Gastric Mapping: A Comparison With Antroduodenal Manometry
Sadaka, C., Xu, B., Benitez, A., Orians, C. M., Bowerman, C., Dourlain, J., Skaggs, B., Konka, K. G., Roshkovan, L., Humphrey, G., et al. (2025) · Neurogastroenterology & Motility · doi:10.1111/nmo.70087 · Cited by 8 · see citing works
“Gastric physiology depends on an intact gastric pacemaker, enteric nervous system (ENS), autonomic system, and bidirectional communication between the ENS and central nervous system (CNS), encompassed within the gut-brain axis [6, 7].”
Effects of Saikosaponin D on Apoptosis, Autophagy, and Morphological Structure of Intestinal Cells of Cajal with Functional Dyspepsia
Zeng, Y., Li, Z., Wan, Y., Fu, T., Xu, P.-D., Zhang, H., & Guan, Y. (2023) · Combinatorial Chemistry & High Throughput Screening · doi:10.2174/0113862073262404231004053116 · Cited by 8 · see citing works
“Drugs regulate gastrointestinal motility by altering the frequency and structure of slow waves [25, 26].”
Background
Neurogastroenterology: Current insights into gastrointestinal innervation in health and disease
Chmelir, T., Jarkovská, D., Pandey, S., & Dvorakova, M. C. (2025) · Autonomic Neuroscience · doi:10.1016/j.autneu.2025.103339 · Cited by 7 · see citing works
Single‐cell RNA sequencing predicts motility networks in purified human gastric interstitial cells of Cajal
Foong, D., Liyanage, L. H., Zhou, J., Zarrouk, A., Ho, V., & O’Connor, M. D. (2021) · Neurogastroenterology & Motility · doi:10.1111/nmo.14303 · Cited by 7 · see citing works
Self-citation
Fenchone Ameliorates Constipation-Predominant Irritable Bowel Syndrome via Modulation of SCF/c-Kit Pathway and Gut Microbiota
Cui, L., Zhang, B., Zou, S., Liu, J., Wang, P., Li, H., & Zhang, Z. (2023) · Journal of Microbiology and Biotechnology · doi:10.4014/jmb.2308.08011 · Cited by 6 · see citing works
“Interstitial cells of Cajal (ICCs) are the main component of the GI tract and are closely correlated with bowel movements [15].”
Background
The Enteric Neuronal Circuitry: A Key Ignored Player in Nutrient Sensing Along the Gut–Brain Axis
Nikolla, E., Grandberry, A., Jamerson, D., Flynn, C. R., & Sundaresan, S. (2025) · The FASEB Journal · doi:10.1096/fj.202500220rr · Cited by 6 · see citing works
Naringenin attenuates slow-transit constipation by regulating the AMPK/mTOR/ULK1 signalling pathway: in vivo and in vitro studies
Wang, Y., Wang, X.-P., Qian, Y.-F., Sun, M., Yang, H.-J., Su, L.-L., & Yan, S. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1550458 · Cited by 10 · see citing works
Bibliometric analysis of nutrition in gastric cancer from 2013 to 2023
Li, R., Zhao, Z., Huang, H., & Yu, J. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1402307 · Cited by 5 · see citing works
Progresses in Questing for the Truth of Opioid‐Related Constipation in Cancer Patients
Liu, M., Sheng, Y., He, Y., Wu, S., Jin, C., & Shen, L. (2025) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.70553 · Cited by 5 · see citing works
“ICC is closely associated with intestinal motility [24].”
An Innovative Model of ISS ‐Based Multiple Fractures and Gastrointestinal Dysfunction Related to c‐Kit Protein Expression on Interstitial Cells of Cajal
Meng, S., Fan, M., Qian, J., Zhang, J., Xu, H., Zheng, Y., Zhao, W., Shan, L., & Huang, J. (2023) · Orthopaedic Surgery · doi:10.1111/os.13599 · Cited by 5 · see citing works
“Gastrointestinal Dysfunction Modeling As the gastrointestinal tract is responsible for digesting food, absorbing nutrients, and releasing waste, its normal functioning is fundamental for maintaining a healthy body.(20,21) Patients with clinically relevant multiple injuries typically suffer gastrointestinal dysfunction…”
Background
Therapeutic effects of three-strain probiotic combination on slow transit constipation: mechanistic insights into MAPK signaling pathway and gut microbiota restoration
Liu, L.-Y., Li, P., Chen, Y., Yang, G.-Y., Cheng, Y., Liu, S., Zhang, X.-R., Wu, Y., Liu, Q.-H., Zhao, P., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1684442 · Cited by 2 · see citing works
Laxative effect of Zengye granule by modulating the SCF/c-Kit pathway and gut microbiota in constipated mice
Lv, F., Li, P., Wang, B., Zhao, M., Ji, P., & Dong, S. (2025) · Frontiers in Veterinary Science · doi:10.3389/fvets.2025.1628570 · Cited by 4 · see citing works
“The proliferation of interstitial cells of Cajal (ICC) is regulated by c-Kit and SCF, which are closely related to gastrointestinal motility (46, 47).”
Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency
Chueh, K., Juan, T.-J., Lu, J., Wu, B., Lin, R., Mao, J.-W., Lin, H., Chuang, S., Chang, C.-Y., Shen, M.-C., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25094927 · Cited by 4 · see citing works
“Sanders et al. described that ICs could be a pacemaker region in the gastrointestinal tract [97] located between nerve endings and smooth muscle cells [98].”
Background
Qi Lang formula relieves constipation via targeting SCF/c-kit signaling pathway: An integrated study of network pharmacology and experimental validation
Li, J., Fu, Y., Wang, Y., Zheng, Y., Zhang, K., & Li, Y. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e31860 · Cited by 4 · see citing works
“Rhythmic slow waves of gastrointestinal muscle contraction are mediated by a variety of cell types, including smooth muscle cells, enteric neurons, telocytes, and ICC [29].”
Background
Gastrale Elektrostimulation bei therapierefraktärer Gastroparese: Ergebnisse einer explorativen Beobachtungsstudie
Iesalnieks, I., von Rebay, N., Patejdl, R., Tiller, M., Müller, T., Schertl, F., Seidl, H., Patejdl, S., Motschmann, M., Roggenbrod, S., et al. (2024) · Zeitschrift für Gastroenterologie - German Journal of Gastroenterology · doi:10.1055/a-2451-0116 · Cited by 4 · see citing works
Quantified motility in Crohn’s disease to evaluate stricture composition using cine-MRI
Beek, K. J., van Rijn, K. L., de Jonge, C. S., de Voogd, F. A. E., Buskens, C. J., van der Bilt, J. D. W., Bemelman, W. A., D’Haens, G., Mookhoek, A., Neefjes‐Borst, A., et al. (2025) · British Journal of Radiology · doi:10.1093/bjr/tqaf120 · Cited by 4 · see citing works
“A possible explanation for the lack of difference in stricture motility among different histopathological subtypes could be a decrease of as well interstitial cells of Cajal 22 as telocytes 23 (involved in gastrointestinal motility 24 ).”
Transcriptome and Proteome Profiling of Primary Human Gastric Interstitial Cells of Cajal Predicts Pacemaker Networks
Foong, D., Mikhael, M., Zhou, J., Zarrouk, A., Liu, X., Schröder, J., Polo, J. M., Ho, V., & O’Connor, M. D. (2023) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm22078 · Cited by 4 · see citing works
“2 April, 2023 (238-249) treatments for GI motility disorders, with the potential to improve the quality of life for millions of patients worldwide.(13) Here, primary human gastric muscle tissues––containing”
BackgroundMethodSelf-citation
Prognostic Significance of Circulating Tumor DNA Mutations in Gastrointestinal Stromal Tumors: A Systematic Review and Meta-analysis Based on Time-To-Event Data
Matheus, G. T. F. U., Ribeiro, D. M., Menegat, A. L. R. S., Menegat, B. L. R. S., Aguiar, I. J. M., Wagner, P. H. D. S., Burbano, R. M. R., & de Moraes, F. C. A. (2025) · Journal of Gastrointestinal Cancer · doi:10.1007/s12029-025-01271-3 · Cited by 3 · see citing works
“These tumors originate from interstitial cells of Cajal (ICCs), which are present throughout the GI tract and play a crucial role in gastrointestinal motility by coordinating peristaltic movements, functioning as specialized pacemaker cells of the GI system [2, 4].”
Effects of Three Microbiome-Based Therapies on Loperamide-Induced Constipation in Mice by Restoring Intestinal Motility and Modulating the Intestinal Microbiota.
Bai, X.-F., Xu, L., Wang, K., Chen, L., Bai, T.-Y., Li, P., Chu, W.-H., & Song, C. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10732-x · Cited by 3 · see citing works
Non-invasive biomagnetic assessment of gastrointestinal motility in a loperamide-induced constipation model
Stoppa, E., Soares, G., Buranello, L. P., Portela, L. M. F., Justulin, L. A., Américo, M., Stasi, L. D. D., & Miranda, J. R. D. A. (2024) · Brazilian Journal of Pharmaceutical Sciences · doi:10.1590/s2175-97902024e23717 · Cited by 3 · see citing works
Predictive value of preoperative ultrasonographic measurement of gastric morphology for the occurrence of postoperative nausea and vomiting among patients undergoing gynecological laparoscopic surgery
Qiu, W., Yin, J., Liang, H., Shi, Q., Liu, C., Zhang, L., Bai, G., Chen, G., & Xiong, L. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1296445 · Cited by 3 · see citing works
Transmembrane protein 16A in the digestive diseases: A review of its physiology, pharmacology, and therapeutic opportunities
Zhang, S., Luo, S., Zhang, H., & Xiao, Q. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.143598 · Cited by 3 · see citing works
Structural Relationships Between Interstitial Cells of Cajal and Smooth Muscle Cells/Nerve Fibers in the Gastric Muscularis Mucosae of Chinese Giant Salamander
Yu, H., Liu, Y., Chu, M., Si, Y., Ye, Y., Ge, T., Zhao, H., & Zhang, H. (2020) · Microscopy and Microanalysis · doi:10.1017/s1431927620024861 · Cited by 3 · see citing works
“It has also been demonstrated that c-Kit/SCF signaling is necessary for the development, differentiation, and phenotype maintenance of ICC (Foong et al., 2020).”
Background
Low-frequency electrical stimulation promotes the recovery of gastrointestinal motility following gynecological laparoscopy (Review)
Wu, Y., Tian, X., Gao, L., & Gao, L. (2022) · Medicine International · doi:10.3892/mi.2022.38 · Cited by 3 · see citing works
Knockdown of miR‐19a suppresses gastrointestinal dysmotility diarrhea after TBI by regulating VIP expression
An, Y., Hu, S. S., Zhang, Y., Song, Z., Li, R., Li, Y., Li, Y., Ren, W., & Wan, P. (2023) · Brain and Behavior · doi:10.1002/brb3.3071 · Cited by 3 · see citing works
“…of gastrointestinal slow-wave potentials, and they are mainly involved in the regulation of basic gastrointestinal electrical rhythms and neurotransmitter signaling, regulating gastrointestinal motility patterns (Daniel, 2010; Foong et al., 2020; Singh et al., 2021; Yadak et al., 2019).”
Background
Trastornos de la interacción cerebro-intestino (trastornos funcionales digestivos), racionalidad para el uso de la neuromodulación
Hernández, D. B. P., Ovalle, L. F. P., Valenzuela, L. M. M., & Mejía, A. C. (2023) · Revista Colombiana de Gastroenterología · doi:10.22516/25007440.997 · Cited by 3 · see citing works
Emodin repairs interstitial cells of Cajal damaged by cholelithiasis in the gallbladder
Huang, Z., & Qiu, H. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1424400 · Cited by 3 · see citing works
Advances in the study of polysaccharides from Anemarrhena asphodeloides Bge.: A review.
An, H., Lin, B.-F., Huang, F., & Wang, N.-N. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.136999 · Cited by 5 · see citing works
GIST and Ghrelin: To Be or Not to Be?
Spiridon, I. A., Ciobanu, D. G. A., Giuşcă, S. E., Ferariu, D., Pleşcă, I., & Căruntu, I.-D. (2021) · Diagnostics · doi:10.3390/diagnostics11081361 · Cited by 3 · see citing works
Opioid-Induced Constipation: Mechanistic Insights, Experimental Models, and Future Perspectives
Lin, Y.-J., Lu, P.-P., Ding, Q., Tao, X., Tan, Q., & Liu, M. (2026) · Biomedicines · doi:10.3390/biomedicines14050995 · Cited by 1 · see citing works
“Beyond peripheral intestinal mechanisms, both the central nervous system (CNS) and interstitial cells of Cajal (ICCs), which serve as the intestinal pacemakers, participate in opioid-mediated inhibition of gut function [11,12].”
Evolution of Esophageal Stricture Treatment by Use of Stents in Benign and Malignant Conditions
Noor, H., Sabău, D., Coțe, A., Mihetiu, A. F., Pirvut, V., Mălinescu, B., & Bratu, D. G. (2024) · Pharmacophore · doi:10.51847/ah7qo6lmzd · Cited by 2 · see citing works
Intracystic gastrointestinal stromal tumor developed in the round ligament of the liver
Kataoka, N., Oura, S., & Furuta, A. (2024) · Radiology Case Reports · doi:10.1016/j.radcr.2024.04.067 · Cited by 2 · see citing works
“ICCs are regarded as the pacemakers of the GI tract [6] , being consistent with the fact that GISTs often occur in organs with high https://doi.org/10.1016/j.radcr. motility in the gastrointestinal tract, e.g., stomach and duodenum.”
BackgroundInfluential
Gastroparesis and Cancer-Related Gastroparesis in Palliative Care Patients
Davis, M. P., Soni, K., & Strobel, S. D. (2024) · Springer eBooks · doi:10.1007/978-3-319-31738-0_114-2 · Cited by 2 · see citing works
Perioperative Gastrointestinal Myoelectric Activity Measurement Using Wireless External Patches
Salimi‐Jazi, F., Thomas, A.-L. A., Wood, L. S. Y., Rafeeqi, T. A., Axelrod, S., Navalgund, A. R., Axelrod, L. A., & Dunn, J. (2024) · Journal of Surgical Research · doi:10.1016/j.jss.2024.07.037 · Cited by 2 · see citing works
Effects and mechanisms of nuciferine on constipation through regulation of the SCF/c-Kit/NF-κB/TLR4 signaling pathway in STC model mice
Zikela, L., Li, X., Zhou, H., Xu, H., Zhu, H., Yu, Z., Wang, D., Gao, J., Ma, Z., Gao, Y., et al. (2025) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2025.110045 · Cited by 2 · see citing works
Vomiting and Gastric Motility in Early Brain Damaged Children With Congenital Zika Syndrome
de Paula, G. L., da Silva, G. A. P., Silva, E. J. D. C. E., Lins, M. D. G. M., Martins, O. S. D. S., Oliveira, D. M. D. S., Ferreira, E. D. S., & Antunes, M. M. D. C. (2022) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0000000000003504 · Cited by 2 · see citing works
“Thus, the absence, decrease, or dysfunction of ICCs can lead to dysrhythmias and gastroparesis (45,46).”
BackgroundMethod
Poor Gastric Emptying in Patients with Paraesophageal Hernias: Pyloroplasty, Per-Oral Pyloromyotomy, BoTox, or Wait and See?
Varvoglis, D. N., & Farrell, T. M. (2022) · Journal of Laparoendoscopic & Advanced Surgical Techniques · doi:10.1089/lap.2022.0342 · Cited by 2 · see citing works
WITHDRAWN: Naringenin attenuates slow-transit constipation by regulating the AMPK/mTOR/ULK1 signaling pathway: In vivo and in vitro studies
Wang, Y., Wang, X., Qian, Y., Sun, M., Yang, H., Su, L., & Yan, S. (2025) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2025.110013 · Cited by 2 · see citing works
Retracted
ИНТЕРСТИЦИАЛЬНЫЕ КЛЕТКИ КАХАЛЯ: КАЛЬЦИЙ-ОПОСРЕДОВАННЫЕ МЕХАНИЗМЫ РЕГУЛЯЦИИ ФУНКЦИЙ
Енгенов, Н. М. (2021) · Университетская клиника · doi:10.26435/uc.v0i1(38).679 · Cited by 1 · see citing works
Utilisation of Deep Neural Networks for Estimation of Cajal Cells in the Anal Canal Wall of Patients with Advanced Haemorrhoidal Disease Treated by LigaSure Surgery
Fišere, I., Edelmers, E., Svirskis, Š., & Groma, V. (2025) · Cells · doi:10.3390/cells14070550
Research progress on the regulation of interstitial cell of Cajal autophagy and apoptosis crosstalk by traditional Chinese medicine in gastrointestinal motility disorders
Zhang, L., Song, Z., Huang, X., Jiang, B., Shen, Y., Li, X., Jiang, X., Wan, J., Xu, Q., Liu, Q., et al. (2025) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2025.120128 · Cited by 1 · see citing works
miR-365-3p Regulates Gastrointestinal Dysfunction in Diabetes Mellitus Rats via the TLR4/MyD88/NF-κB Pathway
Xiao, J., Gao, B., Xiao, Y.-P., & Liu, X. (2025) · Molecular and Cellular Biology · doi:10.1080/10985549.2025.2532581 · Cited by 1 · see citing works
“47 Additionally, it has been shown that hyperglycemia in DM patients leads to changes in the internal and external environments of the ICC, inducing cellular dysfunction and disrupting its function in relation to intestinal smooth muscle.”
SOP: Gastrale Elektrostimulation
Gundling, F., & Pehl, C. (2025) · Gastroenterologie up2date · doi:10.1055/a-2398-7095 · Cited by 1 · see citing works
Therapeutic effects of Poncirus fructus on colonic dysfunction and visceral pain in a zymosan-induced irritable bowel syndrome mouse model through interstitial cells of Cajal and ion channel modulation
Choi, N. R., Ko, S., Choi, W.-G., Jung, D.-H., Kim, S. C., Lim, D. W., Kim, Y. T., Woo, J., Park, J.-W., & Kim, B. J. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1639592 · Cited by 1 · see citing works
Impact of interstitial cells of Cajal on slow wave and gallbladder contractility in a guinea pig model of acute cholecystitis
Ding, F., Guo, R., Chen, F., Liu, L., Cui, Z.-Y., Wang, Y., Zhao, G., & HU, H. X. (2023) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v15.i6.1068 · Cited by 1 · see citing works
Pathogenetic Mechanisms of Peristalsis Disorders in Chronic Constipation
Шевченко, Т. І., Сергеевич, Ш. Д., Abramyan, A. A., & Grekov, I. S. (2024) · I P Pavlov Russian Medical Biological Herald · doi:10.17816/pavlovj321316 · Cited by 1 · see citing works
Exploring the heterogeneity of interstitial cells of Cajal and their properties in gastrointestinal mesenchymal tumors applying single-cell RNA sequencing analysis
Zhu, Y., Zhang, R., Zhang, S., & Hu, H.-J. (2024) · Discover Oncology · doi:10.1007/s12672-024-01372-8 · Cited by 1 · see citing works
DNA methylation of POU5F1 by DNMT1 and DNMT3B triggers apoptosis in interstitial Cajal-like cells via c-kit/SCF inhibition during cholesterol gallstone formation
Liu, Y., Fu, B., He, Q., Bai, X., & Fan, Y. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.167689 · Cited by 1 · see citing works
Distribution of interstitial cells of Cajal in the Esophagus and change in distribution after thoracic trauma
Huang, Z.-P., Wang, K., Qiu, H., He, J.-W., Kong, L.-W., Bai, M., & Cheng, Y.-X. (2022) · Journal of Molecular Histology · doi:10.1007/s10735-022-10074-w · Cited by 1 · see citing works
“ICCs generate and propagate low waves in the alimentary tract (Foong et al. 2020).”
Background
Relieving Effect of Naringenin on Constipation in Mice and Its Effect on Intestinal Flora in Mice
Zhu, X., Liu, X., & Liu, Z. (2023) · Indian Journal of Pharmaceutical Sciences · doi:10.36468/pharmaceutical-sciences.1066 · Cited by 1 · see citing works
“Tryptophan Hydroxylase 1 (TPH1) is a rate-limiting enzyme in 5-HT synthesis[13-15].”
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scRNA-Seq and Network Pharmacology Analysis Reveal SCF/C-kit as the Targeting Mechanism of Qi Lang Formula Relieving ConstipationPreprint
Li, J., Fu, Y., Wang, Y., Zheng, Y., & Li, Y. (2024) · Preprints.org · doi:10.20944/preprints202401.0014.v1 · Cited by 1 · see citing works
Diabetic gastroparesis: pathophysiology and impact on insulin timing choices
Galeano, F., Tumminia, A., Oteri, V., Le Moli, R., Piticchio, T., Scilletta, S., Di Marco, M., Di Pino, A., & Frasca, F. (2026) · Endocrine · doi:10.1007/s12020-026-04693-6
“These cells act as gastrointestinal pacemakers, coordinating the rhythmic contractions necessary for the transit of gastric contents [50, 51].”

Characterising primary human gastric interstitial cells of Cajal
Foong, D. (2026) · Western Sydney University ResearchDirect · doi:10.26183/w7rg-x910
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Interstitial Cells of Cajal: The Pace Maker of the Gastrointestinal Tract
Ramadan, O. I. (2022) · Jordan Journal of Applied Science - Natural Science Series · doi:10.35192/jjoas-n.v16i1.2023
Is there a Role for Human Pluripotent Stem Cells in Modelling Interstitial Cells of Cajal and Gut Motility Disorders?
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Role of the interstitial cells of Cajal in the control of gut motility
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The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy
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Self-citation

Authors: Foong, D., Zhou, J., Zarrouk, A., Ho, V., & O’Connor, M. D.
Affiliations: Western Sydney University (AU)
Campbelltown Private Hospital, Campbelltown, NSW 2560, Australia
Corresponding author: O’Connor, Michael D.
ORCID: Foong, Daphne
Zhou, Jerry
Ho, Vincent
O’Connor, Michael D.
Venue: International Journal of Molecular Sciences
Publisher: MDPI AG
Published: 2020-06-25
Volume: 21
Issue: 12
Pages: 4540
ISSN: 1422-0067 (ISSN-L)
DOI: 10.3390/ijms21124540
PMC: PMC7352366
OpenAlex: W3037610538
Cited by: 127
References: 112
Citations by year: 2026: 14 · 2025: 30 · 2024: 30 · 2023: 22 · 2022: 20 · 2021: 10 · 2020: 1
FWCI: 2.30
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: International Journal of Molecular Sciences (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: University of Western Sydney (N/A)
Australian Rotary Health (N/A)
Topics: Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
Health Sciences › Medicine › Gastroenterology › Gastrointestinal Tumor Research and Treatment
Keywords: interstitial cells of Cajal, gastrointestinal motility, gastroparesis, peristalsis, slow waves, gastric smooth muscle, primary human cells, gastrointestinal motility disorders, therapeutic target
MeSH terms: Gastrointestinal Diseases, Gastrointestinal Motility, Humans, Intestine, Small, Peristalsis, Stomach, Myocytes, Smooth Muscle, Gastrointestinal Tract, Interstitial Cells of Cajal

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Understanding the Biology of Human Interstitial Cells of Cajal in Gastrointestinal Motility

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