In Part I and II of this series of posts, we covered self-organization of ectodermal and endodermal tissues in 3D culture but much of the recent progress in the field of stem cell biology comes from understanding organogenesis in 3D culture in what is really more like 4 dimensions. Whereas self-organization in 3D culture uses artificial scaffolds required for cells to achieve structural formation, 4D stem cell biology involves natural development of complex tissues by following the internal agenda of the cells. Although transplantation of these self-organized tissues may be superior to conventional engineering that is not to say that the additional use of scaffolds and growth factors in tissue engineering would not improve upon the results of stem cell culture and organogenesis.
4D Stem Cell Biology
One intriguing achievement in 4D stem cell biology applications would be retinal transplantation. In fact, clinical trials are currently testing cellular therapy for “dry” macular degeneration with dissociated retinal pigment epithelium cells derived from embryonic stem cells (ESCs). Neural retinal sheet transplantation allows engrafted photoreceptors to make connections to the neural networks in rodent fetal retina, something that will likely be tested in primates next for potential retinitis pigmentosa stem cell therapy.
Another self-formed tissue transplant of interest is gut organoids. Lgr5+ colon stem cell-derived intestinal organoids have already been used for functional transplantation in mouse colon epithelium and thus may be an attractive treatment for human ulcers. These gut organoids may also prove quite valuable in pharmaco-modeling of drugs and investigating absorption and drug interactions in humans.
While complete generation of large organs through self-organization in 3D stem cell culture is still out of reach, various tissue components that make up an organ can be developed, sometimes with minimal intervention thanks to a natural, internal program. The incredible advancements made, even in the last decade, offer hope for providing patients with exceptional treatment options using stem cell-derived tissues and mini-organs. In an era where medicine aims to be more and more personalized, these tissues could be
- combined with gene therapy when transplanted in patients with genetic diseases
- used for genotype- or patient-specific drug screening, especially if iPSCs can be obtained from the patient
- important for in vitro disease modeling using iPSCs specific to the patient or their genotype.
Further research in this area is essential to make the next generation of regenerative medicine a reality and Hemacare can provide the necessary cells to help you get started.
Sasai, Yi. Next-Generation Regenerative Medicine: Organogenesis from Stem Cells in 3D Culture. Cell stem cell 12, no. 5 (2013): 520-530.