# Interviews & Discussions — GCMD Library living collection Updated: n/a · 3 episodes · 40 cited statements ## Episodes ### Bioengineering & Future Directions - [QUAD #14 Future in Bioengineering Solutions with Dr. Michael Helmrath](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104) — video · [machine version](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104.md) - [Growing functional intestinal tissue from stem cells with Dr. Michael Helmrath](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523) — podcast · 8:32 · [machine version](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523.md) - [April 29, 2025 with Michael A. Helmrath, MD](https://library.globalcastmd.com/watch/april-29-2025-with-michael-a-helmrath-md-16337) — video · [machine version](https://library.globalcastmd.com/watch/april-29-2025-with-michael-a-helmrath-md-16337.md) ## Chapters - [0:00](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=0) Introduction to QUAD Conference and Dr. Helmrath (Ep 1) - [0:47](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=47) GI Tract Complexity and Stem Cell-Derived Organoids (Ep 1) - [3:00](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=180) Nerve Integration and Vascular Growth (Ep 1) - [4:40](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=280) Confined Space Culture and Endogenous Nerve Development (Ep 1) - [5:50](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=350) Mesenchyme-Endoderm Recombination Technique (Ep 1) - [7:00](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=420) In Vivo Transplantation and Epithelial Repopulation (Ep 1) - [8:15](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=495) Clinical Translation and Future Applications (Ep 1) - [0:00](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=0) Introduction to QUAD Conference and Dr. Helmrath (Ep 2) - [0:55](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=55) Gut Complexity and Organoid Development Methods (Ep 2) - [1:45](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=105) Organoid Structure and Nerve Integration (Ep 2) - [3:15](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=195) Functional Demonstration of Organoid Peristalsis (Ep 2) - [4:11](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=251) Recombination Technique and Colon Development (Ep 2) - [4:58](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=298) Clinical Application Model: Bowel Damage and Fragment Engraftment (Ep 2) - [6:00](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=360) Translation Pathway and Clinical Delivery Methods (Ep 2) - [7:21](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=441) Future Clinical Applications and Timeline (Ep 2) ## Statements Every statement is attributed, typed, and timestamped; the link is the citation. - The lab has developed methods to grow from a single stem cell drawn from the blood the entire GI tract from the mouth to the anus. — Michael Helmrath (clinical) [Ep 1 · 0:47](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=47) - The first bowel made roughly 11 years ago was small bowel, which was able to be transplanted into the animal. — Michael Helmrath (clinical) [Ep 1 · 1:30](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=90) - Colon transplants into animals but not as well as small bowel, and the antral structures, esophagus and stomach did not and do not readily transplant into the animal. — Michael Helmrath (clinical) [Ep 1 · 1:50](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=110) - When a single organoid is grown in a dish for roughly a month and put into an animal, it is fully laminated and looks no different than a biopsy. — Michael Helmrath (clinical) [Ep 1 · 2:10](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=130) - The transplanted organoid represents the patient from whom the stem cells were derived. — Michael Helmrath (clinical) [Ep 1 · 2:40](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=160) - Nerves are not present in the initial grafts, which are just mesenchyme and endoderm, but nerves can be added by adding to the dish. — Michael Helmrath (clinical) [Ep 1 · 2:50](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=170) - When nerves are present in transplanted grafts, they cause the ingrowth of vasculature that is human, with endothelial progenitors in the graft responding to nerve signals. — Michael Helmrath (clinical) [Ep 1 · 3:10](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=190) - Vascular growth with nerves is important for tissue engineering of the esophagus, requiring both vascular and nervous components. — Michael Helmrath (opinion) [Ep 1 · 3:40](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=220) - Growing cells in a confined space to make a long tube resulted in nerves being co-developed by progenitors within the typical HIO without adding neurospheres externally. — Michael Helmrath (clinical) [Ep 1 · 4:00](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=240) - Nerves formed in confined space culture are very similar to human controls. — Michael Helmrath (clinical) [Ep 1 · 4:40](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=280) - Peristalsis starts in the cells of Cajal in the mesenchyme and is then affected and modulated by the nerve. — Michael Helmrath (clinical) [Ep 1 · 4:55](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=295) - The grafts demonstrate regular peristalsis that can be externally stimulated, and nerve function can be blocked with TTX. — Michael Helmrath (clinical) [Ep 1 · 5:10](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=310) - Relaxation of the grafts can be blocked by L-NAME. — Michael Helmrath (clinical) [Ep 1 · 5:30](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=330) - The lab can separate HIO into endoderm (epithelium, the inside) and mesenchyme (the outside), recombine them, and the result is fully faithful to the original. — Michael Helmrath (clinical) [Ep 1 · 5:50](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=350) - The mesenchyme from HIO can be combined with other endoderms, including colon endoderm. — Michael Helmrath (clinical) [Ep 1 · 6:20](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=380) - In a rat model where bowel was damaged with hot EDTA and a brush, HIO fragments were placed inside the lumen, with somatic stem cells (epithelial only) as controls. — Michael Helmrath (clinical) [Ep 1 · 7:00](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=420) - At seven days after transplantation, control cells showed minimal engraftment, while IPS-generated fragments showed both epithelial and mesenchymal engraftment with cells migrating and proliferating beyond the confined space. — Michael Helmrath (clinical) [Ep 1 · 7:30](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=450) - At 10 weeks after transplantation, nearly the entire epithelium was human, with muscle cells aligned with existing rat cells and fully functional. — Michael Helmrath (clinical) [Ep 1 · 7:55](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=475) - Cincinnati Children's was awarded funding for Organoid Cure to compile data for growing human intestine for patient transplantation and obtain FDA approval. — Michael Helmrath (clinical) [Ep 1 · 8:15](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=495) - The team has developed a hydrogel that polymerizes when exposed to UV light, acting like glue to hold tissue in place without killing cells, allowing cells to migrate out. — Michael Helmrath (clinical) [Ep 1 · 8:40](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=520) - The first clinical step is tissue agnostic, with intestinal transplants serving as a tool to gather information. — Michael Helmrath (opinion) [Ep 1 · 9:05](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=545) - Esophageal strictures are very applicable to this therapy, and Dr. Helmrath anticipates using this therapy in patients this decade. — Michael Helmrath (opinion) [Ep 1 · 9:20](https://library.globalcastmd.com/watch/quad-14-future-in-bioengineering-solutions-with-dr-michael-helmrath-9104?t=560) - The gut includes complexity beyond the epithelial lining: nerves, muscles, immune system, luminal bacteria recognition, and microbiota. — Michael Helmrath (clinical) [Ep 2 · 0:55](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=55) - The first bowel made roughly 11 years ago was small bowel, which was able to be transplanted into the animal. — Michael Helmrath (clinical) [Ep 2 · 1:25](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=85) - Colon transplants into animals but not as well as small bowel, while antral structures (esophagus and stomach) did not and do not readily transplant into the animal. — Michael Helmrath (clinical) [Ep 2 · 1:34](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=94) - Nerves are not present in the grafts initially; they are just mesenchyme and endoderm, but nerves can be added by adding neurosphere to the dish when transplanting. — Michael Helmrath (clinical) [Ep 2 · 2:05](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=125) - When nerves are present in grafts, they cause the ingrowth of human vasculature; cells in the graft that are endothelial progenitors are told what to do by nerves. — Michael Helmrath (clinical) [Ep 2 · 2:20](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=140) - Nerve presence is important for tissue used for the esophagus. — Michael Helmrath (clinical) [Ep 2 · 2:31](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=151) - Growing cells in a confined space to make a long tube resulted in nerves co-developing by progenitors within the typical HIO without adding neurospheres. — Michael Helmrath (clinical) [Ep 2 · 2:40](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=160) - Peristalsis starts in the cells of Cajal and the mesenchyme, then is affected and modulated by the nerve. — Michael Helmrath (clinical) [Ep 2 · 3:26](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=206) - The tissue demonstrates the ability to both contract and relax, which are important properties for building esophagus. — Michael Helmrath (clinical) [Ep 2 · 4:02](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=242) - HIOs can be separated in a dish with the inside being epithelium/endoderm and the outside being mesenchyme, like an Oreo cookie, and can be recombined with any mesenchyme. — Michael Helmrath (clinical) [Ep 2 · 4:11](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=251) - When separated and recombined, the mesenchyme and endoderm remain fully faithful to their original identity. — Michael Helmrath (clinical) [Ep 2 · 4:29](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=269) - A rat model was developed by dividing the bowel and damaging it with hot EDTA and a brush, then placing HIO fragments inside the lumen. — Michael Helmrath (clinical) [Ep 2 · 4:58](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=298) - At 7 days after fragment placement, IPS-generated fragments show both epithelial engraftment (staining brown for human KU 80) and mesenchymal engraftment, while control somatic stem cells rarely show engraftment. — Michael Helmrath (clinical) [Ep 2 · 5:22](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=322) - Cincinnati Children's was awarded Organoid Cure funding to put together data to grow human intestine to put into a patient and obtain FDA approval. — Michael Helmrath (clinical) [Ep 2 · 6:14](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=374) - Working with Georgia Tech, the team developed a hydrogel that when exposed to UV light polymerizes like glue and holds tissue in place without killing cells, allowing cells to migrate out. — Michael Helmrath (clinical) [Ep 2 · 6:50](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=410) - The first step is tissue agnostic, with intestinal transplant serving as a tool to gather information. — Michael Helmrath (opinion) [Ep 2 · 7:21](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=441) - Diseases like esophageal strictures are very applicable to this therapy. — Michael Helmrath (opinion) [Ep 2 · 7:31](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=451) - Dr. Helmrath anticipates using this therapy within the current decade in patients. — Michael Helmrath (opinion) [Ep 2 · 7:31](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=451) ## Host summaries Recaps by a host of what the experts said — not the host's own clinical position. - The lab has developed methods to grow from a single stem cell drawn from blood the entire GI tract from mouth to anus. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 1:16](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=76) - A single organoid grown in a dish for roughly a month and transplanted into an animal produces human intestine on top of the kidney of the mouse that is fully laminated and looks no different than a biopsy. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 1:45](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=105) - Nerves formed in confined space growth are much better compared to when added externally and are very similar to human controls. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 3:15](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=195) - Grafts can be externally stimulated and nerve function can be blocked with TTX, and relaxation can be blocked by L-NAME. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 3:36](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=216) - L-NAME hydrochloride can be used in animal modeling to construct cardiovascular and cerebrovascular disease models and has been widely applied for several decades as an antagonist of nitric oxide synthase. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 3:47](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=227) - The mesenchyme from HIO can be combined with other endoderms to create different tissue types including colon. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 4:44](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=284) - The cells migrate in a non-confined space such that at 10 weeks the whole epithelium is human, with muscle cells aligned with existing rat cells and fully functional. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 5:40](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=340) - A custom accelerator space is dedicated to translating the team's work with world-class scientists. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 6:29](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=389) - The hydrogel delivery method could be used for recalcitrant strictures by dilating, spraying cells, and applying UV light to keep cells localized. — Em Gootee summarizes what Dr. Michael Helmrath said [Ep 2 · 6:59](https://library.globalcastmd.com/watch/growing-functional-intestinal-tissue-from-stem-cells-with-dr-michael-helmrath-16523?t=419) --- Educational content from recorded physician discussions — not medical advice. 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