Formation of 3D tissues of primary hepatocytes using fibrillized collagen microparticles as intercellular binders

The potential of organoids in toxicologic pathology: role of toxicologic pathologists in <i>in vitro</i> chemical hepatotoxicity assessment

“…From the perspective of toxicologic pathologists, hepatocytes with collagen microfibrils and bile canaliculi were closely packed in composite spheroids on hematoxylin and eosin (HE)-stained specimens. Morita et al 32 also demonstrated that fibrilized collagen microparticles, as intercellular binders, are useful for forming hepatocyte-based 3D tissues, resulting in a thick but planar morphology that is stably maintained in HE-stained sections. Future improvements in the microparticles and sizes of collagens are expected to better establish the conditions for maintaining the function and morphology of 3D hepatocytes.…”

“…Thus, several morphological variations exist in liver organoids, probably depending on the degree of cell differentiation; however, branching morphogenesis seems obscure 53 . When evaluating hepatocytotoxicity in vitro , the most common method is to collect whole treated cells and detect CYP induction, cell death, and cell proliferation while checking the degree of hepatocyte differentiation (albumin and urea production) 31 , 32 , 61 , 63 . However, in the case of organoids, it may be possible to detect more detailed toxic reactions by histopathologically confirming the type of organoid ( Fig.…”

A multiscale, vertical-flow perfusion system with integrated porous microchambers for upgrading multicellular spheroid culture

“…20,21 Additionally, incorporation of microengineered biomaterials, especially microparticles and microfibers composed of extracellular matrix components, has been shown to be highly effective in enhancing the cell–matrix interactions within spheroids. 22–24…”

“…20,21 Additionally, incorporation of microengineered biomaterials, especially microparticles and microfibers composed of extracellular matrix components, has been shown to be highly effective in enhancing the cellmatrix interactions within spheroids. [22][23][24] Typical methods of forming spheroids include, but are not limited to, the use of non-cell-adherent dishes, 25 hanging drop method, 26 rotational cultures, 27 and microfabricated chambers. 22,28,29 Among these techniques, microchamberbased cultivation is the most capable of precisely controlling the spheroid size and morphology in a high-throughput manner without necessitating complicated operations and devices.…”