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Background Emerging evidence suggests that 'fibroblast-like cells' (FLC) may play a role in the regulation of gastrointestinal (GI) motor function. FLC are ultrastructurally distinct from other interstitial cells, including interstitial cells of Cajal (ICC), and express small-conductance Ca2+-activated K+ channels (SK3). In mice, platelet-derived growth factor receptor α (PDGFR α) antibody has also been shown to label FLC. The aims of this study were to determine the morphology and distribution of PDGFR α-immunoreactive (ir) FLC in human gastric muscle and to determine if FLC are altered in gastroparesis, where ICC are reduced. Methods Full thickness gastric body biopsies from five healthy subjects, 10 diabetic, and 10 idiopathic gastroparesis patients were immunolabeled using SK3 and PDGFR α staining for FLC and Kit staining for ICC. Intramuscular FLC and ICC were quantified. Key Results Intramuscular PDGFR α-ir cells had slender cell bodies and long, thin processes and were more abundant in the longitudinal compared with the circular muscle. In the region of myenteric plexus, FLC had smaller, rounder cell bodies with 3-4 processes and formed networks, often around ganglia. All SK3-ir cell structures showed complete overlap with PDGFR α-ir. FLC were in close proximity to ICC, but their cell bodies did not overlap. No differences were seen in the distribution, morphology, or overall numbers of FLC in gastroparesis patients. Conclusions & Inferences In conclusion, PDGFR α identifies FLC in human gastric smooth muscle. FLC were not altered in distribution or overall numbers in gastroparesis. Additional studies are required to determine their role in human GI function. [ABSTRACT FROM AUTHOR]