{"id":17490,"date":"2022-08-31T18:42:36","date_gmt":"2022-08-31T18:42:36","guid":{"rendered":"https:\/\/clinlabint.com\/?p=17490"},"modified":"2022-08-31T18:42:36","modified_gmt":"2022-08-31T18:42:36","slug":"organoid-production-breakthrough-to-help-accelerate-disease-and-drug-development-research","status":"publish","type":"post","link":"https:\/\/clinlabint.com\/organoid-production-breakthrough-to-help-accelerate-disease-and-drug-development-research\/","title":{"rendered":"Organoid production breakthrough to help accelerate disease and drug development research"},"content":{"rendered":"
\n

\r\n\"Bio-Rad<\/a>\r\n<\/p>\n<\/div><\/section><\/div>

<\/p>\n<\/div><\/section>
\n

Organoid production breakthrough to help accelerate disease and drug development research<\/h1>\/ in E-News<\/a> <\/span><\/span><\/header>\n<\/div><\/section>
\n

As the idea of growing tiny human organs in lab dishes has moved in recent years from futuristic science fiction to actual bioscientific reality, the usefulness of organoids as a research tool for studying the digestive system swiftly encountered a bottleneck \u2013 these valuable tissues are quite difficult to make.<\/h3>\n

<\/p>\n

Even with highly trained teams using all the best ingredients and equipment, one batch of starting material can generate lots of tiny spheroids of organ precursor cells that can then be grown into specific organoid types. But the next batch may produce few spheroids or none at all.<\/p>\n

As a result, lab teams often experience delays making the organoids they need for pre-clinical experiments that seek to test the safety or potency of potential medications or for basic research to delve deeper into the genetic and molecular activities that cause disease.<\/p>\n

Now, in a paper published June 28, 2022, in Stem Cell Reports, a team of experts at Cincinnati Children\u2019s reports developing a method that overcomes this production bottleneck. The new method already is being used to advance organoid studies within the medical centre. But since the materials involved can be frozen and thawed and still produce high-quality organoids, this discovery makes it possible to ship starter materials to other labs anywhere in the world \u2013 which could spark dramatically accelerated use of human gastrointestinal organoids throughout medical research.<\/p>\n

\u201cThis method can make organoids a more accessible tool,\u201d says first author Amy Pitstick, MS, manager of the Pluripotent Stem Cell Facility at Cincinnati Children\u2019s. \u201cWe show that the aggregation approach consistently produces high yields and we have proven that precursor cells can be thawed from cyrogenic storage to produce organoids of the small intestine.\u201d<\/p>\n

Chris Mayhew, PhD, corresponding author and director of the Pluripotent Stem Cell Facility, said: \u201cUsing this approach will make it possible for many research labs to use organoids in their experiments without the time and expense of learning how to grow induced pluripotent stem cells (iPSCs. The ability to freeze the precursor cells also will allow labs to easily make organoids without having to start each new experiment with complicated and highly variable iPSC differentiation.\u201d<\/p>\n

The new process<\/strong><\/h4>\n

Typically, organoid production requires collecting skin or blood cells that are converted in the lab to make iPSCs. To use these to make intestinal organoids, highly trained lab staff grow a flat layer of organ precursor cells called the midhindgut endoderm.<\/p>\n

Given the right conditions, early-stage organoids called spheroids spontaneously form into 3D balls of cells. These get collected and transferred into a growth medium that provides the necessary signals for the cells to form into the specific cell types of a human organ \u2013 in this case the small intestine.<\/p>\n

But the number of spheroids generated this way has proven inconsistent. The Cincinnati Children\u2019s team determined it was possible to collect the unused precursor cell layer and use a centrifuge to drive cells into hundreds of tiny wells contained on small plastic plates. This prompts the formation of 3D cell aggregates that can be collected and used for organoid production.<\/p>\n

The paper notes that testing shows that the spheroids made this way have no meaningful differences from those that grew spontaneously. Next, the team placed samples of the precursor cells into freezers for storage. Once these cells were thawed and aggregated, they also formed viable spheroids.<\/p>\n

The paper confirms that these spheroids can be reliably grown into more mature organoids that mimic the functions of the small intestine, the large intestine (colon) and the bottom portion of the stomach that connects to the intestines (antrum).<\/p>\n

Potential uses for mass-produced organoids<\/strong><\/h4>\n

Even with this advance, it will require years of work to develop organoids large enough and sophisticated enough to use as replacement tissue in transplant surgery. But having lots of easy-to-produce organoids opens many doors for medical research.<\/p>\n

\u2022 More labs will be able to make patient-specific organoids to test drug combinations for precision treatment of complex conditions or rare disease states that require customized care.
\n\u2022 Scientists doing basic research to learn more about the genetic factors and molecular mechanisms at work in diseases affecting the digestive tract will be able to use organoids by ordering frozen spheroid precursors for their experiments.
\n\u2022 Labs testing ways to grow larger organoids for potential transplantation would obtain less expensive, more-reliable supplies of large numbers of human organoids for their research.
\n\u2022 And a new generation of biomedical research students will have much easier access to human organoids to study without needing to learn how to grow iPSCs.<\/p>\n

Michael Helmrath, MD, Director of Clinical Translation for the Center for Stem Cell & Organoid Medicine (CuSTOM) at Cincinnati Children\u2019s, already has started using materials made from the new process in his ongoing research to develop transplantable intestinal tissues.<\/p>\n

\u201cThis is a great step forward for the field on many fronts,\u201d Helmrath says. \u201cTo be able to reduce the complexity of the process and provide higher yields is beneficial to our work. And to be able to translate the methods to other labs will help move regenerative medicine forward.\u201d<\/p>\n<\/div><\/section>
\n

\"\"<\/div><\/div><\/div>
\n

Human intestine organoids growing in wells of a lab dish as part of a study at Cincinnati Children’s demonstrating a new mass production method for gut organoids. Cincinnati Children’s<\/strong><\/p>\n<\/div><\/section>
\n

Reference:<\/strong><\/em>
\nPitstick A. et. al. Aggregation of cryopreserved mid-hindgut endoderm for more reliable and reproducible hPSC-derived small intestinal organoid generation. Stem Cell Reports. 28 July 2022. doi: https:\/\/doi.org\/10.1016\/j.stemcr.2022.06.011<\/a><\/p>\n<\/div><\/section>
\n