Organoids

3D culture systems that mimick organ structures and thus organ development.

—> show cell sorting

—> self organization

—> enable differentiation of different cell types

• three dimensional, pea-size

• differentiation of different cell types

• cell sorting + self-organization

• recapitulation of development and AdSC niches

• pluripotent stem cells: ESCs, iPSCs

• adult stem cells

• put SCs into culture that recapitulates ECM (e.g. matrigel)

• no surface adhesion, allow self-organization

• provide medium that allows terminal differentiation + good nutrient supply

• provide activators and repressors of key signaling pathways to recapitulate developmental process

for AdSC organoids:

• use medium and culturing method that recapitulates niche environment

Brain organoids

• from PSCs

• first culture in simple medium —> embryoid bodies

• transfer into matrigel: differentiation into pseudostratified neuroepithelial structures (default)

• cultivation in spinning bioreactor + supply of different factors allows good nutrient supply and formation of different cerebral structures and cell types (glia, neurons, radial glia, astrocytes)

Intestinal organoids

• either from PSCs or ISCs

• provide key signaling factors allow recapitulation of developmental process

• for AdSCs: WNT, EGF, FGF, inhibit BMP and TGFb

  • only generates epithelial cell types of intestine

Liver Organoids

• either from PSCs or from duct cells

• provide key signaling factors allow recapitulation of developmental process

• for AdSCs: recapitulate niche signals and inhibit TGFb

  • only generates epithelial cell types of liver

• induced pluripotent stem cells

• improved cell culture techniques

• improved knowledge of developmental processes

• regenerative/ personalized medicine, patient-specific therapy

• drug screening

• disease development

• tissue specific studies of infectous diseases

• biobanks

• organ development

• future: tissue replacement approaches

Brain organoids

• Zika virus infections (virus tropism)

• studies on microcephaly (microcephaly organoids show premature differentiation and thus decreased cell numbers)

Intestinal organoids

• studies on intestinal cancer development

• effect of APC knockout

• if derived from tumors or patient-derived iPSCs: personalized therapies, drug testing

Liver organoids

• study of infectious diseases e. g. hepatitis

• liver cirrhosis studies

• also cancer and personalized medicine approaches

• new and upcoming approach/technique that promises many new opportunities for biomedical research

• “human” model organism

• may decrease need of animal models, no animal protection laws etc, no animal suffering

• patient-derived organoids enable precise study of diesease mechanisms and treatment possibilities

• maybe in future: more defined recapitulation of developmental processes could enable culturing of entire organs —> TISSUE REPLACEMENT THERAPIES

• they only mimick organ structures

• no tissue interactions

• no precise recapitulation of organ structures

• limited in size

• limited reproducibility, varying protocols

• no interaction with native tissue microenvironments

• no interactions with immune cells etc

• when derived from AdSCs: mostly epithelial cell types

• studies of viral entry

• studies of viral replication

• cell-specific tropism, infection of particular cell types

  • e.g use of alveolar and bronchial organoids (derived from ATII cells or club cells)

• drug testing (e.g. imatinib reduced virus replication?)

• infection mechanism, pathology, progression