Organoid-based regenerative medicine
Organoid-based regenerative medicine is a promising new direction in transplantology, which will allow in the near future to replace damaged or worn-out organs and tissues of patients with young transplants grown from their own rejuvenated cells.
Tissue 3D self-organization in vitro
An organoid is a self-organized 3D tissue that is typically derived from stem cells (pluripotent, fetal or adult), and which mimics the key functional, structural and biological complexity of an organ. Cells comprising organoids can be derived from induced pluripotent stem cells (iPSCs) or tissue-derived cells (TDCs), including normal stem/progenitor cells, differentiated cells and cancer cells. Recent studies on the directed differentiation of human pluripotent stem cells report tissue self-organization in vitro such that multiple component cell types arise in concert and arrange with respect to each, thereby recapitulating the morphogenetic events typical for that organ. Such self-organization has generated pituitary, optic cup, liver, brain, intestine, stomach and kidney.[1]
Organ-supply imbalance
The outstanding progress in all types of transplantation during recent years has dramatically increased graft and patient survival. But one of the major limiting factors for further developing organ donation and transplant programs is a worldwide organ shortage. Globally, there is a large gap between the numbers of potential recipients on waiting lists and the available organs for transplant.[2]
Stem cell-related technologies promise to generate organs from patients’ cells. Adult cells can be reprogrammed into induced pluripotent stem cells (iPSC). These constitute an extensive source of a starting material which is able to differentiate into any tissue. Moreover, being autologous, they bypass the problem of incompatibility and rejection of the graft by the host immune system. To this end, iPSCs have already been used successfully in animal models of diabetes, liver injury, myocardial infarction and Parkinson’s disease.
Organoids that can be transplanted into damaged tissues to induce regeneration are currently being actively studied due to their fundamental treatment effects for various disease.[3][4]
Liver Organoids
Organoids of murine intestines, livers and pancreas have been successfully transplanted into mice with restoration of organ function.[5][6] The company LyGenesis, hopes to save people with devastating liver diseases who are not eligible for transplants. Their approach is to inject liver cells from a donor into the lymph nodes of sick recipients, which can give rise to entirely new miniature organs. These mini livers should help compensate for an existing diseased one. The approach appears to work in mice, pigs, and dogs. Now it's time to check if it works in people.
Cardiac organoids
PSC-derived 3D cardiac organoids have been shown to be beneficial for drug toxicity screening and disease modeling. Although, there are remaining limitations that need to be addressed prior to clinical translation and potentially achieving cardiac regeneration. First, the rigor of stem cell reprogramming needs to ensure there is no clonal or somatic genetic variation in the starting material, as well as the standardization of differentiation protocols that yield highly specific and a large number of purified cell populations at the manufacturing level. To date, cardiac organoids do not fully recapitulate native human heart tissue as they lack perfusable vessels, adult-like chamber specificity, and the cardiac conduction system.[7]
Kidney organoids
Three-dimensional (3D) kidney organoid models have been developed that can be grown either from induced pluripotent stem cells (iPSCs), first described in 2014, or from adult stem/progenitor cells (ASPCs). [8]
References
- ↑ Zhao, Z., Chen, X., Dowbaj, A. M., Sljukic, A., Bratlie, K., Lin, L., ... & Yu, H. (2022). Organoids. Nature Reviews Methods Primers, 2(1), 94. https://doi.org/10.1038/s43586-022-00174-y
- ↑ Lewis, A., Koukoura, A., Tsianos, G. I., Gargavanis, A. A., Nielsen, A. A., & Vassiliadis, E. (2021). Organ donation in the US and Europe: The supply vs demand imbalance. Transplantation Reviews, 35(2), 100585. PMID: 33071161 DOI: 10.1016/j.trre.2020.100585
- ↑ Choi, W. H., Bae, D. H., & Yoo, J. (2023). Current status and prospects of organoid-based regenerative medicine. BMB reports, 56(1), 10-14. PMID: 36523211 PMCID: PMC9887105 DOI: 10.5483/BMBRep.2022-0195
- ↑ Tang, X. Y., Wu, S., Wang, D., Chu, C., Hong, Y., Tao, M., ... & Liu, Y. (2022). Human organoids in basic research and clinical applications. Signal Transduction and Targeted Therapy, 7(1), 168. PMID: 35610212 PMCID: PMC9127490 DOI: 10.1038/s41392-022-01024-9
- ↑ Weng, Y., Han, S., Sekyi, M. T., Su, T., Mattis, A. N., & Chang, T. T. (2023). Self-Assembled Matrigel-Free iPSC-Derived Liver Organoids Demonstrate Wide-Ranging Highly Differentiated Liver Functions. Stem Cells, 41(2), 126-139. PMID: 36573434 PMCID: PMC9982071 DOI: 10.1093/stmcls/sxac090
- ↑ Messina, A., Luce, E., Benzoubir, N., Pasqua, M., Pereira, U., Humbert, L., ... & Dubart-Kupperschmitt, A. (2022). Evidence of adult features and functions of hepatocytes differentiated from human induced pluripotent stem cells and self-organized as organoids. Cells, 11(3), 537. PMID: 35159346 PMCID: PMC8834365 DOI: 10.3390/cells11030537
- ↑ Martin M., Gähwiler E.K.N., Generali M., Hoerstrup S.P., Emmert M.Y. (2023). Advances in 3D Organoid Models for Stem Cell-Based Cardiac Regeneration. International Journal of Molecular Sciences. 24(6):5188. https://doi.org/10.3390/ijms24065188
- ↑ Shi, M., McCracken, K. W., Patel, A. B., Zhang, W., Ester, L., Valerius, M. T., & Bonventre, J. V. (2023). Human ureteric bud organoids recapitulate branching morphogenesis and differentiate into functional collecting duct cell types. Nature Biotechnology, 41(2), 252-261. PMID: 36038632 PMCID: PMC9957856 DOI: 10.1038/s41587-022-01429-5
