scholarly journals Advances in development and application of human organoids

3 Biotech ◽  
2021 ◽  
Vol 11 (6) ◽  
Author(s):  
Abhijith Shankaran ◽  
Keshava Prasad ◽  
Sima Chaudhari ◽  
Angela Brand ◽  
Kapaettu Satyamoorthy

AbstractInnumerable studies associated with cellular differentiation, tissue response and disease modeling have been conducted in two-dimensional (2D) culture systems or animal models. This has been invaluable in deciphering the normal and disease states in cell biology; the key shortcomings of it being suitability for translational or clinical correlations. The past decade has seen several major advances in organoid culture technologies and this has enhanced our understanding of mimicking organ reconstruction. The term organoid has generally been used to describe cellular aggregates derived from primary tissues or stem cells that can self-organize into organotypic structures. Organoids mimic the cellular microenvironment of tissues better than 2D cell culture systems and represent the tissue physiology. Human organoids of brain, thyroid, gastrointestinal, lung, cardiac, liver, pancreatic and kidney have been established from various diseases, healthy tissues and from pluripotent stem cells (PSCs). Advances in patient-derived organoid culture further provides a unique perspective from which treatment modalities can be personalized. In this review article, we have discussed the current strategies for establishing various types of organoids of ectodermal, endodermal and mesodermal origin. We have also discussed their applications in modeling human health and diseases (such as cancer, genetic, neurodegenerative and infectious diseases), applications in regenerative medicine and evolutionary studies.

2019 ◽  
Vol 11 (11) ◽  
pp. 968-981 ◽  
Author(s):  
Weiwei Liu ◽  
Chunhao Deng ◽  
Carlos Godoy-Parejo ◽  
Yumeng Zhang ◽  
Guokai Chen

2019 ◽  
Author(s):  
Richard L Carpenedo ◽  
Sarah Y Kwon ◽  
R Matthew Tanner ◽  
Julien Yockell-Lelièvre ◽  
Chandarong Choey ◽  
...  

SummaryHuman pluripotent stem cells (hPSCs) are an essential cell source in tissue engineering, studies of development, and disease modeling. Efficient, broadly amenable protocols for rapid lineage induction of hPSCs are of great interest in the stem cell biology field. We describe a simple, robust method for differentiation of hPSCs into mesendoderm in defined conditions utilizing single-cell seeding (SCS) and BMP4 and Activin A (BA) treatment. Gene sets and gene ontology terms related to mesoderm and endoderm differentiation were enriched after 48 hours of BA treatment. BA treatment was readily incorporated into existing protocols for chondrogenic and endothelial progenitor cell differentiation. After prolonged differentiation in vitro or in vivo, BA pre-treatment resulted in higher mesoderm and endoderm levels at the expense of ectoderm formation. These data demonstrate that SCS with BA treatment is a powerful method for induction of mesendoderm that can be integrated into protocols for mesoderm and endoderm differentiation.


Author(s):  
Jiyoon Lee ◽  
Karl Koehler

Abstract Skin is a complex and vulnerable tissue that it is challenging to reconstitute once damaged. Here, we describe a three-dimensional organoid culture system that can generate fully stratified skin with its appendages from human pluripotent stem cells. This in vitro-based skin organoid culture system will benefit investigations into basic skin biology and disease modeling, as well as translational efforts to reconstruct or regenerate skin tissue.


2021 ◽  
Vol 7 (3) ◽  
pp. 364
Author(s):  
Ya Ren ◽  
Xue Yang ◽  
Zhengjiang Ma ◽  
Xin Sun ◽  
Yuxin Zhang ◽  
...  

Organoids developed from pluripotent stem cells or adult stem cells are three-dimensional cell cultures possessing certain key characteristics of their organ counterparts, and they can mimic certain biological developmental processes of organs in vitro. Therefore, they have promising applications in drug screening, disease modeling, and regenerative repair of tissues and organs. However, the construction of organoids currently faces numerous challenges, such as breakthroughs in scale size, vascularization, better reproducibility, and precise architecture in time and space. Recently, the application of bioprinting has accelerated the process of organoid construction. In this review, we present current bioprinting techniques and the application of bioinks and summarize examples of successful organoid bioprinting. In the future, a multidisciplinary combination of developmental biology, disease pathology, cell biology, and materials science will aid in overcoming the obstacles pertaining to the bioprinting of organoids. The combination of bioprinting and organoids with a focus on structure and function can facilitate further development of real organs.


Cell Medicine ◽  
2018 ◽  
Vol 10 ◽  
pp. 215517901877375 ◽  
Author(s):  
Jessica N Mazerik ◽  
Steven Becker ◽  
Paul A Sieving

Across scientific disciplines, 3-D organoid culture systems offer platforms to integrate basic research findings with clinical care. The National Eye Institute mounted a $1.1 million 3-D Retina Organoid Challenge. Organoids developed through the Challenge will be valuable resources for drug screening, disease modeling, and precision and regenerative medicine.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A652-A652
Author(s):  
Hugo E J Vankelecom ◽  
Emma Laporte ◽  
Florian Hermans ◽  
Charlotte Nys ◽  
Annelies Vennekens

Abstract The pituitary gland harbors a population of stem cells. However, role and regulation of these cells remain poorly understood. We recently established organoids from mouse pituitary as a novel research tool to explore pituitary stem cell biology (Cox et al., J. Endocrinol. 2019; 240:287-308). In general, organoids represent 3D in vitro cell configurations that develop and self-organize from (single) tissue stem cells under well-defined culture conditions that typically mirror the stem cell niche and/or embryogenic processes. Organoids reliably recapitulate key aspects of the original organ, including of its stem cell compartment. Moreover, organoids are long-term expandable while retaining these properties. We demonstrated that pituitary organoids originate from the resident (SOX2+) stem cells, largely phenocopy these cells and retain the stemness phenotype during expansive culture. Interestingly, the organoids show confident in vivo translatability and, when developed from transgenically damaged gland, recapitulate the activation status of the stem cells as observed in situ following injury. Now, we found that the organoids also mirror the stem cells’ phenotype and biology in physiological conditions in which the stem cell compartment is either activated or compromised. Organoids from the neonatal maturing pituitary reproduce phenotypical and functional aspects of its activated stem cells, whereas organoids from aging gland mimic the declined functional state of the stem cells in old pituitary. Interestingly, this functional decay was found to be reverted during organoid culture, indicating that the old pituitary stem cells retain intrinsic functionality but are in vivo restrained by an obstructive microenvironment, not present in the organoid culture. Indeed, using single-cell transcriptomics and in vivo analysis, we found that the aging pituitary suffers from a prevailing inflammatory state (inflammaging) which appears to raise the threshold for stem cell activation. Interestingly, comparison of young and old pituitary led us to the discovery of pituitary stem cell activators. Finally, we found that activated parameters of organoid formation are also observed when tumorigenesis takes place in the gland, again mimicking the in situ stem cell activation that is occurring in this perturbed, pathological condition. Taken together, we identified, and applied, our new pituitary organoid model as advanced and powerful tool to gain profound insight into pituitary stem cell behavior across life and disease, which is expected to eventually translate into restorative and rejuvenative tactics when pituitary function is compromised by damage or age. In this context, our single-cell transcriptome database has strong potential to unveil appealing targets.


Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1531 ◽  
Author(s):  
Kilian Mazaleyrat ◽  
Cherif Badja ◽  
Natacha Broucqsault ◽  
Raphaël Chevalier ◽  
Camille Laberthonnière ◽  
...  

Induced pluripotent stem cells (iPSCs) obtained by reprogramming primary somatic cells have revolutionized the fields of cell biology and disease modeling. However, the number protocols for generating mature muscle fibers with sarcolemmal organization using iPSCs remain limited, and partly mimic the complexity of mature skeletal muscle. Methods: We used a novel combination of small molecules added in a precise sequence for the simultaneous codifferentiation of human iPSCs into skeletal muscle cells and motor neurons. Results: We show that the presence of both cell types reduces the production time for millimeter-long multinucleated muscle fibers with sarcolemmal organization. Muscle fiber contractions are visible in 19–21 days, and can be maintained over long period thanks to the production of innervated multinucleated mature skeletal muscle fibers with autonomous cell regeneration of PAX7-positive cells and extracellular matrix synthesis. The sequential addition of specific molecules recapitulates key steps of human peripheral neurogenesis and myogenesis. Furthermore, this organoid-like culture can be used for functional evaluation and drug screening. Conclusion: Our protocol, which is applicable to hiPSCs from healthy individuals, was validated in Duchenne Muscular Dystrophy, Myotonic Dystrophy, Facio-Scapulo-Humeral Dystrophy and type 2A Limb-Girdle Muscular Dystrophy, opening new paths for the exploration of muscle differentiation, disease modeling and drug discovery.


2018 ◽  
Vol 2 (1) ◽  
pp. 3-5
Author(s):  
Mridha Sharma ◽  
Kirandeep Kaur

The human body is an intricate system consisting of numerous cells and tissues working in an organized fashion for the sustenance of life and stem cell biology become an important field for the understanding of tissue regeneration and implementation of regenerative medicine. Stem cells have capability of replicating themselves and can be readily available at the time of a planned procedure. Furthermore, it’s been shown that these cells have high potential to serve as resources not for medical therapies and tissue engineering, but also for dental or bone reconstruction. Stem cell research is not merely a science fiction but has rather opened the door for future treatment modalities.


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