View source for 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.<ref>Wu, Y., Ye, W., Gao, Y., Yi, Z., Chen, Z., Qu, C., ... & Liu, Z. (2023). Application of organoids in regenerative medicine. Stem Cells, sxad072.  PMID: 37724396 DOI: 10.1093/stmcls/sxad072</ref><ref>Soto-Gamez, A., Gunawan, J. P., Barazzuol, L., Pringle, S., & Coppes, R. P. (2024). Organoid-based personalized medicine: from tumor outcome prediction to autologous transplantation. Stem Cells, sxae023. PMID: 38525972 [https://doi.org/10.1093/stmcls/sxae023 DOI: 10.1093/stmcls/sxae023]</ref> 

== 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.<ref>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</ref>

=== 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.<ref>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</ref>

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.<ref>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</ref><ref>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</ref>

=== Liver Organoids ===
Organoids of murine intestines, livers and pancreas have been successfully transplanted into mice with restoration of organ function.<ref>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</ref><ref>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</ref>
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.<ref>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</ref>

=== 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).
<ref>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</ref>

===Retinal organoids ===
Age-related macular degeneration (AMD) is the most common cause of blindness in the western world. Poor vision due to AMD can cause negative consequences, such as increased risk of falls, depression, lack of meaningful activities in daily life, and requirement of long-term care.<ref>Jiang, B., Jiang, C., Li, J., & Lu, P. (2023). Trends and disparities in disease burden of age-related macular degeneration from 1990 to 2019: Results from the global burden of disease study 2019. Frontiers in Public Health, 11, 1138428. PMID: 37265519 PMC10231224 DOI: 10.3389/fpubh.2023.1138428</ref>
3D organoids of the eyeball<ref>Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., … & Sasai, Y. (2011). Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature, 472(7341), 51-56</ref> and the retina with photoreceptor cells: rods and cones have been developed.<ref>Völkner, M., Zschätzsch, M., Rostovskaya, M., Overall, R. W., Busskamp, V., Anastassiadis, K., & Karl, M. O. (2016). Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis. Stem cell reports, 6(4), 525-538. PMID: 27050948 PMC4834051 DOI: 10.1016/j.stemcr.2016.03.001</ref><ref>Lowe, A., Harris, R., Bhansali, P., Cvekl, A., & Liu, W. (2016). Intercellular adhesion-dependent cell survival and ROCK-regulated actomyosin-driven forces mediate self-formation of a retinal organoid. Stem cell reports, 6(5), 743-756. PMID: 27132890 PMC4939656 DOI: 10.1016/j.stemcr.2016.03.011</ref> This allow in the nearest future to develop treatments for [[Aging and eye disease|eye diseases]] such as retinal degeneration.<ref>Bohrer, L. R., Stone, N. E., Mullin, N. K., Voigt, A. P., Anfinson, K. R., Fick, J. L., ... & Tucker, B. A. (2023). Automating iPSC generation to enable autologous photoreceptor cell replacement therapy. Journal of translational medicine, 21(1), 161. PMID: 36855199 PMCID: PMC9976478 DOI: 10.1186/s12967-023-03966-2</ref><ref>Bose, D., Ortolan, D., Farnoodian, M., Sharma, R., & Bharti, K. (2023). Considerations for Developing an Autologous Induced Pluripotent Stem Cell (iPSC)-Derived Retinal Pigment Epithelium (RPE) Replacement Therapy. Cold Spring Harbor Perspectives in Medicine, a041295-a041295. PMID 37487631 doi:10.1101/cshperspect.a041295</ref><ref>Mandai, M. (2023). Pluripotent stem cell-derived retinal organoid/cells for retinal regeneration therapies: A review. Regenerative Therapy, 22, 59-67. PMID 36712956 PMC 9841126 doi:10.1016/j.reth.2022.12.005</ref><ref>Akiba, R., Takahashi, M., Baba, T., & Mandai, M. (2023). Progress of iPS cell-based transplantation therapy for retinal diseases. Japanese Journal of Ophthalmology, 67(2), 119-128. PMID 36626080 doi:10.1007/s10384-022-00974-5</ref>

=== Cerebral organoids ===
Human cerebral organoids (HCOs) are models that grow up in the laboratory and mimic the cellular composition, structure and function of parts of the adult human brain. Brain organoids are an exciting new technology with the potential to significantly change how diseases of the brain are understood and treated.<ref>D’Antoni, C., Mautone, L., Sanchini, C., Tondo, L., Grassmann, G., Cidonio, G., ... & Di Angelantonio, S. (2023). Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders. International Journal of Molecular Sciences, 24(13), 10762.PMID: 37445940 PMC10341866 DOI: 10.3390/ijms241310762</ref><ref>Kim, H., Jang, E. J., Sankpal, N. V., Patel, M., & Patel, R. (2023). Recent Development of Brain Organoids for Biomedical Application. Macromolecular Bioscience, 23(3), 2200346. PMID: 36469016 DOI: 10.1002/mabi.202200346</ref>

Researchers have transplanted young glial progenitor cells into adult chimeric mice brains and found that they not only [[ Cell Competition|'''competed with and replaced''']] unhealthy cells but '''aged''' ones, too. The findings open the door to developing an effective treatment for a range of conditions like multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer’s disease, autism and schizophrenia.<ref>Vieira, R., Mariani, J. N., Huynh, N. P., Stephensen, H. J., Solly, R., Tate, A., ... & Goldman, S. A. (2023). Young glial progenitor cells competitively replace aged and diseased human glia in the adult chimeric mouse brain. Nature Biotechnology, 1-12. PMID: 37460676 DOI: 10.1038/s41587-023-01798-5</ref>

== References ==
<references />

== For better understanding ==
What is known about early human development.  
* Wu et al. (2024). [https://doi.org/10.1016/j.cell.2024.05.027 Toward developing human organs via embryo models and chimeras] 
* Ramos et al. (2024). [https://doi.org/10.1016/j.cell.2024.05.016 Parsing patterns: Emerging roles of tissue self-organization in health and disease]

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