Not yet reviewed by Pith; the record is open.

Medical image segmentation requires not only accuracy but also robustness under challenging imaging conditions. In this study, we show that a carefully configured DeepLabv3 model can achieve high performance in segmenting induced pluripotent stem (iPS) cell colonies, and, under our experimental conditions, outperforms large-scale foundation models such as SAM2 and its medical variant MedSAM2 without structural modifications. These results suggest that, for specialized tasks characterized by subtle, low-contrast boundaries, increased model complexity does not necessarily translate to better performance. Our work revisits the assumption that ever-larger and more generalized architectures are always preferable, and provides evidence that appropriately adapted, simpler models may offer strong accuracy and practical reliability in domain-specific biomedical applications. We also offer an open-source implementation that includes strategies for small datasets and domain-specific encoding, with the aim of supporting further advances in semantic segmentation for regenerative medicine and related fields.