Interstitial cells of Cajal and human colon motility in health and disease
Open accessAbstract
Our understanding of human colonic motility, and autonomic reflexes that generate motor patterns, has increased markedly through high-resolution manometry. Details of the motor patterns are emerging related to frequency and propagation characteristics that allow linkage to interstitial cells of Cajal (ICC) networks. In studies on colonic motor dysfunction requiring surgery, ICC are almost always abnormal or significantly reduced. However, there are still gaps in our knowledge about the role of ICC in the control of colonic motility and there is little understanding of a mechanistic link between ICC abnormalities and colonic motor dysfunction. This review will outline the various ICC networks in the human colon and their proven and likely associations with the enteric and extrinsic autonomic nervous systems. Based on our extensive knowledge of the role of ICC in the control of gastrointestinal motility of animal models and the human stomach and small intestine, we propose how ICC networks are underlying the motor patterns of the human colon. The role of ICC will be reviewed in the autonomic neural reflexes that evoke essential motor patterns for transit and defecation. Mechanisms underlying ICC injury, maintenance, and repair will be discussed. Hypotheses are formulated as to how ICC dysfunction can lead to motor abnormalities in slow transit constipation, chronic idiopathic pseudo-obstruction, Hirschsprung's disease, fecal incontinence, diverticular disease, and inflammatory…
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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 [51]
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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
“204,205 SCF, a growth factor, is vital for ICC development and maintenance, while c ‐ kit serves as a receptor for SC. 206,207 SCF and c ‐ kit signaling are essential for ICC survival, differentiation, and function, which are crucial for regulating gastric motility and emptying.”
BackgroundIdiopathic Slow Transit Constipation: Pathophysiology, Diagnosis, and Management
Vlismas, L. J., Wu, W. K. K., & Ho, V. (2024) · Medicina · doi:10.3390/medicina60010108 · Cited by 55 · see citing works
“Patients may also have abnormal or reduced numbers of interstitial cells of Ca-jal [4,7,15,18], and in the majority of cases of patients who have undergone colectomy for refractory STC, histological examination shows an abnormal or reduced number of ICCs [11].”
BackgroundRevised spectral metrics for body surface measurements of gastric electrophysiology
Schamberg, G., Varghese, C., Calder, S., Waite, S., Erickson, J., O'Grady, G., & Gharibans, A. (2022) · medRxiv · doi:10.1111/nmo.14491 · Cited by 39 · see citing works
“…approach can be problematic, because normal cutaneous gastric myoelectrical recordings commonly show transient high-amplitude bursts of low frequency noise ( 2 cpm) occurring concurrently with stable gastric activity of normal frequency, 12 likely representing colonic activity, 20,21 or artifacts.”
BackgroundInterstitial cells of Cajal: clinical relevance in pediatric gastrointestinal motility disorders
Friedmacher, F., & Rolle, U. (2023) · Pediatric surgery international (Print) · doi:10.1007/s00383-023-05467-1 · Cited by 27
“Several subtypes of ICCs have been distinguished according to their distinct distribution patterns and morphological features within the anatomical layers of the gastrointestinal tract [34].”
BackgroundGastrointestinal Dysfunction in Parkinson’s Disease
Safarpour, D., Sharzehi, K., & Pfeiffer, R. F. (2022) · Drugs · doi:10.1007/s40265-021-01664-1 · Cited by 36 · see citing works
“The cause is suspected to be dysfunction within the ENS as a consequence of abnormal or reduced number of interstitial cells of Cajal in the myenteric plexus of the colon [267, 268].”
BackgroundLuteolin ameliorates loperamide-induced functional constipation in mice
Wang, Y., Jiang, H., Wang, L., Gan, H., Xiao, X., Huang, L., Li, W., & Li, Z. (2023) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x2023e12466 · Cited by 24 · see citing works
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Self-citationThe role of colonic motility in low anterior resection syndrome
Varghese, C., Wells, C., Bissett, I., O’Grady, G., & Keane, C. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.975386 · Cited by 22 · see citing works
“The anatomy and functioning of ICC in the colon have been comprehensively outlined in a recent review (34).”
BackgroundInfluentialWang, Y.-H., Wang, L., Ni, X., Jiang, M., & Zhao, L.-Z. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1291524 · Cited by 21 · see citing works
The Crucial Role of the Interstitial Cells of Cajal in Neurointestinal Diseases
Choi, E. L., Taheri, N., Tan, E., Matsumoto, K., & Hayashi, Y. (2023) · Biomolecules · doi:10.3390/biom13091358 · Cited by 22 · see citing works
“…Biomolecules 2023 , 13 , 1358 2 of 18 smooth muscle contractions, and mediating nitrergic and cholinergic neuromuscular neurotransmission; and other regulatory interstitial cells and muscularis macrophages (MMs), a specialized type of immune cell found in the muscular layer of the GI tract [4,5].”
BackgroundPatejdl, R. (2024) · Visceral Medicine · doi:10.1159/000542156 · Cited by 18
Myths and misconceptions about childhood constipation
Rajindrajith, S., Devanarayana, N., Thapar, N., & Benninga, M. (2023) · European Journal of Pediatrics · doi:10.1007/s00431-023-04821-8 · Cited by 16 · see citing works
“It has, indeed, been shown that both adults and children with slow transit constipation may have significant microstructural abnormalities [20, 21, 95].”
BackgroundLin, A., Varghese, C., Paskaranandavadivel, N., Seo, S., Du, P., Dinning, P., Bissett, I., & O'Grady, G. (2021) · medRxiv · doi:10.1111/codi.16249 · Cited by 16
“While, the role of cyclic motor patterns in constipation is incompletely understood [18], some studies have demonstrated that increased retrograde rectosigmoid motility and pressure may impair bowel motions [53– 55].”
BackgroundImmune niches orchestrated by intestinal mesenchymal stromal cells lining the crypt-villus
Sun, H., Tan, J., Chen, H., Wu, N., & Su, B. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1057932 · Cited by 18 · see citing works
Tang, X., Huang, Y., Jiang, T., Wu, J., Wang, K., & Wu, W. (2025) · BMC Gastroenterology · doi:10.1186/s12876-025-04387-9 · Cited by 14 · see citing works
The human colon: Evidence for degenerative changes during aging and the physiological consequences
Baidoo, N., & Sanger, G. J. (2024) · Neurogastroenterology & Motility · doi:10.1111/nmo.14848 · Cited by 12 · see citing works
Li, J., Bai, J., Tuerdi, N., & Liu, K. (2022) · Bioengineered · doi:10.1080/21655979.2022.2054501 · Cited by 14 · see citing works
“ICC plays a critical role in the peristaltic contractions of the gastrointestinal and urinary tract by generating a rhythmic depolarization and transmitting it to the musculature [1,4].”
BackgroundLiu, J., Ji, L., Wang, Y., Chen, X., Wan, Y., Qian, H., & Zhang, D. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.119139 · Cited by 13 · see citing works
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Telocytes and Other Interstitial Cells 2.0: From Structure to Function
Crețoiu, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232416221 · Cited by 11
“In the diverse landscape of cellular components found in the interstitial space, there are distinct populations that can be grouped according to the functions they perform in: (a) cells with a supporting role, also acting as immune regulators, e.g., fibroblastic reticular cells [2]; (b) cells with a role in the synthe…”
BackgroundInfluentialGrape seed powder increases gastrointestinal motility
Choi, N.-R., Kim, J., Kwon, M., Lee, J.-R., Kim, S. C., Lee, M. J., Choi, W., & Kim, B. (2022) · International Journal of Medical Sciences · doi:10.7150/ijms.72529 · Cited by 11 · see citing works
“Abnormalities in ICCs have been implicated in GI motility disorders [12,30,31].”
BackgroundWang, 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
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
“+e density, structure, and distribution of ICC are related to the initiation and conduction of gastrointestinal slow waves, which govern the motility of the gastrointestinal tract [32].”
BackgroundGao, Z., Fu, L.-W., Bai, W., & Liang, J.-W. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1598806 · Cited by 6
Zhang, P., Zhu, Y., Chen, P., Zhou, T., Han, Z.-Y., Xiao, J., Ma, J.-F., Ma, W., Zang, P., & Chen, Y. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i1.96199 · Cited by 6 · see citing works
Understanding the potential causes of gastrointestinal dysfunctions in multiple system atrophy
Craig, C. F., Finkelstein, D. I., McQuade, R. M., & Diwakarla, S. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106296 · Cited by 8 · see citing works
Laxative effect of Wenyang Yiqi Decoction on loperamide-induced astriction model mice
Su, Y., Zhu, R., Pang, C.-X., He, Z., Wu, B.-S., & Wang, X.-P. (2023) · Annals of Translational Medicine · doi:10.21037/atm-23-6 · Cited by 6 · see citing works
“ICCs partake in the GI elementary electrical rhythm governance and neurotransmitter signaling, which are main factors in the elementary functions of the GI meshwork (31).”
Sun, M., Zhao, M., Du, L., Hou, J., Dong, J., & Zhang, B. (2025) · Food Bioscience · doi:10.1016/j.fbio.2025.106711 · Cited by 5 · see citing works
Zou, S., Xie, B., An, Z., Li, F., Cui, L., Zhang, Z.-H., Bu, W., & He, D.-D. (2025) · Drug Design, Development and Therapy · doi:10.2147/dddt.s517114 · Cited by 5 · see citing works
“39 Gas stimulates gastric acid secretion and enhances peristalsis in the gastrointestinal tract, promoting the .”
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
“The ICCs function as both a “metronome” and “pacemaker” for intestinal smooth muscle cells or a “bridge” connecting intestinal neurons with intestinal smooth muscle cells [14].”
Mo, L.-Y., Ma, K.-Y., Li, Y., Song, J.-F., Song, Q., & Wang, L. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1550880 · Cited by 5 · 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
Colonic Electrical Stimulation for Chronic Constipation: A Perspective Review
Ortego-Isasa, I., Ortega-Morán, J., Lozano, H. E., Stieglitz, T., Sánchez-Margallo, F., Usón-Gargallo, J., Pagador, J., & Ramos-Murguialday, A. (2024) · Biomedicines · doi:10.3390/biomedicines12030481 · Cited by 5 · see citing works
“Furthermore, intra-muscular ICCs are present in longitudinal and circular muscles that mediate neural stimuli while other ICCs located in the subserosa may influence the activity of the longitudinal muscle layer [28].”
BackgroundLiu, S.-F., Zhao, Y., Li, S., Li, Y.-N., Liu, L., Sheng, J., Tian, Y., & Gao, X.-Y. (2023) · Gene · doi:10.1016/j.gene.2023.148064 · Cited by 5 · see citing works
Plasticity of colonic enteric nervous system following spinal cord injury in male and female rats
Werner, C. M., Willing, L. B., Goudsward, H. J., McBride, A. R., Stella, S., & Holmes, G. M. (2023) · Neurogastroenterology and Motility · doi:10.1111/nmo.14646 · Cited by 5 · see citing works
“53 Modeling studies propose that network oscillations are resistant to some degree of ICC loss, 54 while other studies have identified diabetic gain- of-function accompanied by ICC expansion.”
BackgroundTian, G., Wang, B., Kong, B., Yuan, Z., Yang, Y., Wang, Z., Liu, D., & Zhao, S.-P. (2025) · Neurogastroenterology and Motility · doi:10.1111/nmo.70128 · Cited by 4 · see citing works
The Ageing of the Human Lower Bowel
Baidoo, N., & Sanger, G. J. (2025) · British Journal of Hospital Medicine · doi:10.12968/hmed.2024.0734 · Cited by 3 · see citing works
miR-10a-5p and miR-10b-5p restore colonic motility in aged mice
Baek, G., Singh, R., Ha, S., Cho, H., Padmanabhan, S., Vishwanath, V., Kim, M., Seon, D., You, J., Lee, M.-Y., et al. (2025) · World Journal of Gastroenterology · doi:10.3748/wjg.v31.i24.104437 · Cited by 4 · see citing works
Pathogenesis of Disorders of the Motor Function of the Large Intestine in Functional Constipation
Galagudza, M. M., Uspensky, Y. P., Fominykh, Y. A., & Butko, D. Y. (2024) · Russian Journal of Gastroenterology Hepatology Coloproctology · doi:10.22416/1382-4376-2024-34-3-24-37 · Cited by 4 · see citing works
Rodriguez, G. M., Kirshblum, S., Thao, M., Mcarthur, M., & Camilleri, M. (2024) · Journal of Clinical Medicine · doi:10.3390/jcm13061527 · Cited by 4 · see citing works
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Zhao, S., & Tong, W. (2023) · Journal of Neurogastroenterology and Motility · doi:10.5056/jnm22181 · Cited by 4
“The interstitial cells of Cajal (ICC) are well known for their pacemaker activity in the gastrointestinal (GI) tract.(1-3) ICC generate spontaneous rhythmic depolarizations that are passively conducted to adjacent smooth muscle cells (SMCs) through gap junctions.”
BackgroundChoi, N.-R., Jeong, H.-R., Choi, W., Park, J.-W., Ko, S.-J., & Kim, B. (2023) · International Journal of Medical Sciences · doi:10.7150/ijms.83986 · Cited by 4 · see citing works
“, mice, guinea pigs, and dogs) has revealed that ICCs act as pacemakers in the stomach, small intestine, and large intestine [7,8].”
Veličkov, A., Djordjevic, B., Lazarević, M., Veličkov, A., Petrovič, V., Jović, M., Denčić, T., & Radenković, G. (2023) · Medicina · doi:10.3390/medicina59020308 · Cited by 6 · see citing works
“Immunohistochemical labeling of PDGFRα enables identification of IPC, PDGFRα-positive interstitial “fibroblast-like” cells [10].”
BackgroundInfluentialAi, L.-L., Zhang, L.-L., Liang, Q., Tian, Y., Chen, T., & Wu, C. (2022) · Frontiers in Sustainable Food Systems · doi:10.3389/fsufs.2022.1010556 · Cited by 4 · see citing works
“Although they make up only 5% of the cells in the muscle tissue of the gastrointestinal tract, they play a key role in regulating smooth muscle function and gastrointestinal movement in harmony with the enteric nervous system (Huizinga et al., 2021).”
BackgroundGut motility as a driver of microbial community architecture and host-microbe evolution.
Schwalbe, M., Bosch, T., & Aidy, S. E. (2026) · Trends in Microbiology · doi:10.1016/j.tim.2025.12.016 · Cited by 3 · see citing works
Bai, X., Xu, L., Wang, K., Chen, L., Bai, T., Li, P., Chu, W., & Song, C. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10732-x · Cited by 3 · see citing works
Sung, T., Ko, S.-J., Choi, W., Park, J.-W., & Kim, B. (2025) · International Journal of Medical Sciences · doi:10.7150/ijms.116169 · Cited by 3
“The regulation of gastrointestinal (GI) motility involves a finely tuned interplay among enteric neurons, smooth muscle cells, PDGFRα + cells, and interstitial cells of Cajal (ICCs), which serve as pacemakers responsible for initiating peristaltic and segmental movements [1-3].”
Study on the Effect and Mechanism of Weichang'an Pill and Its Extract on Slow Transit Constipation
Wang, N., Lu, X., Gao, P., Zhang, P., Wang, Y., Miao, L., Zhang, H., & Chai, L. (2025) · Neurogastroenterology and Motility · doi:10.1111/nmo.70052 · Cited by 3 · see citing works
Doguet, M., Oster, J., Malka-Mahieu, H., Doyen, M., & Odille, F. (2023) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society · doi:10.1109/embc40787.2023.10340911 · Cited by 3
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
Crippa, J., Achilli, P., Origi, M., Roufael, F., Sassun, R., del Re, L., Montroni, I., Belotti, D., Sivieri, F., Magistro, C., et al. (2025) · Journal of Minimal Access Surgery · doi:10.4103/jmas.jmas_284_24 · Cited by 2
“[15] Furthermore, peristalsis and colonic motility could be better preserved through the maintenance of proximal nerve fibres originating from the SHA.”
Xiong, H., He, T., Tang, J., Chu, J., & He, P. (2025) · Digestive Diseases and Sciences · doi:10.1007/s10620-025-09559-x · Cited by 2 · see citing works
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
DREADDs‐Based Chemogenetics Induced Slow Transit Constipation via Inhibition of Enteric Neurons
Lu, X.-Y., Wen, Y.-X., Jiang, N., Zhou, S.-Q., Yang, T., Shi, L.-L., Guo, H.-M., Zhang, W., Zhang, Q.-P., & Zhang, N. (2025) · Journal of Digestive Diseases · doi:10.1111/1751-2980.13344 · Cited by 2
“Decreased intestinal nerve activity, accompanied by changes in neurotransmitters and muscle activity, may be observed in most STC patients [29, 30].”
Genome‐Wide DNA Methylation and Copy Number Alterations in Gastrointestinal Stromal Tumors
Kleijn, T., Ameline, B., Bleckman, R., Kooistra, W., van den Broek, E., Diercks, G. F. H., van Hemel, B. V., Timmer, B., Timens, W., Kats-Ugurlu, G., et al. (2025) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.70046 · Cited by 2
“It is well established that GISTs arise from the interstitial cells of Cajal (ICC) or their stem cell precursors, and at least four distinct subpopulations of ICC have been identified, with specific distributions in the gastrointestinal tract [34].”
Aldisi, D., Alyami, S. H., Alhamdan, A., Alebrahim, H. M., Almadani, A., & Abulmeaty, M. (2024) · Actas espanolas de psiquiatria · doi:10.62641/aep.v52i6.1734 · Cited by 2
“GMA is a slow wave rhythm and spike potential that originates from the pacemaker interstitial cells of Cajal [12].”
Majeed, K., Jaafar, H. A., & Rasol, H. M. (2024) · JPMA. The Journal of the Pakistan Medical Association · doi:10.47391/jpma-bagh-16-97 · Cited by 2
“Abnormalities are linked to GI motility problems and diseases 4,5 .”
BackgroundAnorectal physiology and colonic motility in children with a history of tethered cord syndrome.
van der Zande, J. M. J., Srinivas, S., Koppen, I., Benninga, M., Wood, R. J., Sanchez, R. E., Puri, N. B., Vaz, K. K. H., Yacob, D., Lorenzo, C. D., et al. (2024) · Journal of Pediatric Gastroenterology and Nutrition - JPGN · doi:10.1002/jpn3.12357 · Cited by 2
Liu, Z.-N., Wang, C., Shen, Y.-L., Shi, Y.-F., Duan, J., Dong, H.-J., Xu, Y.-B., Zheng, Y.-M., & Cui, H. (2026) · Frontiers in Oncology · doi:10.3389/fonc.2026.1904273 · Cited by 1 · see citing works
“ICCs are responsible for generating and propagating gastrointestinal slow-wave activity and are essential for coordinated intestinal motility; their dysfunction has been associated with a range of gastrointestinal motility disorders (53, 54).”
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
“They receive excitatory or inhibitory signals from enteric neurons (such as ACh and NO), integrate and amplify these signals, and subsequently transmit them to smooth muscle cells to initiate or suppress contractions, thereby generating intestinal slow waves and peristalsis [72].”
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
Local Myoelectric Sensing During Human Colonic Tissue Perfusion
David, M. M. B., Makwana, R., Yered, T., Sanger, G. J., Knowles, C. H., Wasserberg, N., & Shor, E. (2024) · Diagnostics · doi:10.3390/diagnostics14242870 · Cited by 1 · see citing works
Structural Alterations in Diverticular Disease
Lopez, K. E., & Maguire, L. H. (2024) · Clinics in Colon and Rectal Surgery · doi:10.1055/s-0044-1791283 · Cited by 1
“25 Colonic ICCs are signi fi cantly reduced in number in diverticular disease, and a recent ultrastructural study noted that ICCs in the myenteric plexus demonstrated signs of injury in patients with chronic complicated disease, but not in diverticulosis alone.”
A bibliometric analysis of interstitial cells of Cajal research
Li, P.-Y., Xiao, Y.-D., Zhou, L., Zhang, X.-Y., Xu, Y., Wang, X.-J., Zou, M.-L., & Guo, X. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1391545 · Cited by 1 · see citing works
Li, H., Ji, Y., Luo, H.-S., Huizinga, J., & Chen, J.-H. (2024) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.18343 · Cited by 1 · see citing works
“31,45 The networks of ICC are key players in the control of gastrointestinal motility for generating electrical pacemaker activity (rhythmic slow oscillations of membrane potential) that provide the musculature with the mechanism to produce propulsive rhythmic contractile activity, 31,45,46 and are…”
BackgroundSelf-citationMeligy, A. S., Alakkad, A., Almahameed, F. B., & Chehal, A. (2022) · Asian Journal of Medicine and Health · doi:10.9734/ajmah/2022/v20i11753 · Cited by 1 · see citing works
“ICC functions as a pacemaker in regulating motility [4].”
BackgroundHuang, 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
“Studies have confirmed that ICCs are distributed in the lower esophageal sphincter, stomach, colon and so on Huizinga et al. 2021; Otsuka et al. 2021; Wang TH et al. 2021).”
BackgroundDiabetic 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].”
Animal Models of Slow-Transit Constipation: Current Progress, Limitations, and Future Perspectives.
Ren, Y.-C., Jiao, Y.-R., & Li, J. (2026) · Digestive Diseases and Sciences · doi:10.1007/s10620-026-10270-8
Popivanov, G., Ilcheva, B., Konaktchieva, M., Cirocchi, R., Tabakov, M., Pavlov, V., & Mutafchiyski, V. (2026) · Reports · doi:10.3390/reports9040339
“The submuscular ICCs are the dominant cells generating the so-called “slow wave” with rhythmic depolarisation at three cycles/min, named “the signature of ICC pacemaker activity” by Huizinga et al. [10].”
InfluentialMontini, F., Pittock, S. J., Cacciaguerra, L., Weiner, H. L., & Schwerdtfeger, L. (2026) · Annals of Neurology · doi:10.1002/ana.78380
“65 GI transit time can be regulated by numerous neurotransmitters, 59,60 interstitial cells of Cajal, 66 and enteric glia.”
Fan, J., Jiang, Y., Luan, X., Wang, X., Wang, X., Zhang, X., Tian, J., Xin, X., Qiu, W., & Qi, W. (2026) · Inflammation Research · doi:10.1007/s00011-026-02360-0
“2 ) [ 267, 268 ].”
Xie, N., Su, G.-H., Wu, Y., Peng, K., Mei, Z., Chen, W., Xu, K., & Li, B.-W. (2026) · Neurogastroenterology and Motility · doi:10.1111/nmo.70439
Baccari, M. C., Nistri, S., Cinelli, E., Mutolo, D., & Idrizaj, E. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27188373
Ertürk, Z., Nielsen, K., Jakobsen, L. M., Gottlieb, A. D., Bertram, H. C., Roager, H., & Karabanov, A. (2026) · bioRxiv · doi:10.64898/2026.08.13.744397
“Alterations in gastric slow waves, including reductions in interstitial cells of Cajal density, have been observed in motility disorders such as slow-transit constipation 18,19 .”
Chen, Y., Duan, W., Du, M., Guo, M., & Sun, Y. (2026) · Frontiers in Microbiology · doi:10.3389/fmicb.2026.1817279
“SCFAs can modulate enteric neuronal activity and intestinal smooth muscle function (Bruning et al., 2020), whereas serotonin signaling influences ICC-mediated neuromuscular coordination (Huizinga et al., 2021).”
Luo, W., Wang, Z.-Q., Xiao, J.-Y., Xiao, L.-M., Liang, K., Luo, M., & Lu, W.-H. (2026) · Pathology, Research and Practice · doi:10.1016/j.prp.2026.156640
Dispelling myths and misconceptions of constipation with a focus on stimulant laxatives
Lacy, B. E., Brenner, D. M., Serra, J., Pohl, D., Andresen, V., & Aran, A. (2026) · Frontline Gastroenterology · doi:10.1136/flgastro-2025-103547
Wang, Y., Zhen, S., Sun, M., Su, L., & Yan, S. (2026) · Neurogastroenterology & Motility · doi:10.1111/nmo.70341
“Studies have demonstrated that con-stipated rats exhibit significantly reduced numbers of colonic ICCs [6] and ultrastructural damage, as evidenced by mitochondrial swelling and autophagic vesicle formation [7], suggesting that mitochondrial dysfunction may be a potential factor contributing to…”
osr1 as a Novel Marker for ICC‐Like Cells Development in Zebrafish
Yang, W., Tan, X., He, P., He, Z.-W., Zhang, Y., Tian, T., Li, Y., Yu, T., Li, F.-R., Zhang, M.-Z., et al. (2026) · Cell Biology International · doi:10.1002/cbin.70162
“In recent years, ICCs have garnered increasing interest in both physiological and clinical research (Friedmacher and Rolle 2023; Huizinga et al. 2021), owing to their critical roles in gastrointestinal function and their involvement in various diseases (Kishi et al. 2020; López‐Pingarrón et al.…”
Intestinal electromagnetic modeling and current density inversion for functional assessment
Guo, J., Zhang, Z.-H., Zhang, T.-Y., Zhao, X.-Y., Zhang, R., Yin, L., Zhao, Z.-M., Song, F., Liang, L., & Han, L. (2026) · Biocybernetics and Biomedical Engineering · doi:10.1016/j.bbe.2026.03.006
Ma, K.-Y., Song, X., Teng, C., Hu, X., Xu, L., Ye, D., Chai, Z., Lu, Y., Feng, J., & Li, Y. (2026) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2026.152054
CFD protein deficiency induce slow transit constipation is correlated with gut microbial dysbiosis
Hu, S., Liu, H., Song, F., Huang, D., & Wei, Q. (2026) · Scientific Reports · doi:10.1038/s41598-026-41597-x
Rusu, M., Pirici, D., Varga, I., & Nicolescu, M. (2026) · Annals of Anatomy · doi:10.1016/j.aanat.2026.152812
Gong, W., Bu, F., Dai, Q., Xu, J.-L., & Yu, P. (2026) · Journal of Molecular Histology · doi:10.1007/s10735-025-10698-8
“Slow transit constipation (STC), a common subtype of functional constipation, is clinically characterized by colonic motility dysfunction accompanied by delayed colonic content transit, reduced defecation frequency, and dry stool (O’Donnell et al., 2024; Huizinga et al. 2021).”
Fišere, I., Edelmers, E., Svirskis, Š., & Groma, V. (2025) · Cells · doi:10.3390/cells14070550
“Further research, incorporating individual features of HD patients and involving a larger cohort, may provide deeper insights into the complex biology of the disease [51,52].”
Wang, H., Zhao, B., Huang, L., Zhu, X., Li, N., Huang, C., Han, Z., & Ouyang, K. (2024) · Journal of Gastroenterology · doi:10.1007/s00535-024-02164-1
“It has been widely recognized that ICCs play a pacemaker role in the GI tract, in which they are responsible for the generation of slow waves and determine the frequency of intestinal contractions [42, 48, 58, 67–69].”
Kapur, R. (2024) · Pediatric and Developmental Pathology · doi:10.1177/10935266241235507
“31 ICC are stellate cells with relatively small cell bodies, round nuclei, and multiple thin long processes.”
BackgroundTsymbalyuk, O., Hurskyi, L. A., Davydovska, T., Voiteshenko, I., Sholota, K., Kozolup, M., Savchenko, O., Naumenko, A., & Skryshevsky, V. (2023) · Studia Biologica · doi:10.30970/sbi.1701.706
Kirichek, P. (2024) · CHERKASY UNIVERSITY BULLETIN BIOLOGICAL SCIENCES SERIES · doi:10.31651/2076-5835-2018-1-2024-1-29-34
“…result of disorders in coordinated activity of central and autonomic nervous system, humoral motility regulation of the gastrointestinal tract, blood circulation deterioration in the submucosa and muscular layer of the intestine, dystrophy of neurons in the intermuscular neuron plexus, etc. [8-10].”
Background
- Authors
- Huizinga, J. D., Hussain, A., & Chen, J.-H.
- Affiliations
- McMaster University (CA)
- Corresponding author
- Huizinga, Jan D.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2021-11-01
- Volume
- 321
- Issue
- 5
- Pages
- G552-G575
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- OpenAlex
- W3202068022
- Cited by
- 108
- References
- 155
- Citations by year
- 2026: 22 · 2025: 27 · 2024: 24 · 2023: 18 · 2022: 17
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Gouvernement du Canada | Canadian Institutes of Health Research (152942)
- Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (1293408)
- Farncombe Family Digestive Health Research Institute, McMaster University
- Canada Foundation for Innovation
- Hamilton Academic Health Sciences Organization
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Surgery › Congenital gastrointestinal and neural anomalies
- Health Sciences › Medicine › Gastroenterology › Gastroesophageal reflux and treatments
- Keywords
- interstitial cells of Cajal, colonic motility, enteric nervous system, colonic manometry, slow transit constipation, Hirschsprung disease, fecal incontinence, diverticular disease, inflammatory bowel disease, defecation
- MeSH terms
- Animals, Autonomic Nervous System, Colon, Colonic Diseases, Colonic Pseudo-Obstruction, Constipation, Defecation, Fecal Incontinence, Gastrointestinal Motility, Hirschsprung Disease, Humans, Manometry, Enteric Nervous System, Interstitial Cells of Cajal
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