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Human iPSC intestine mimetics with integrated mesenchymal, endothelial and enteric nervous tissue

Award Number: R01DK137806
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2024
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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Human iPSC intestine mimetics with integrated mesenchymal, endothelial and enteric nervous tissue - In this proposal, we present exciting preliminary data showing that we have generated an iPSC-derived human intestinal organoid (HIO) model that co-differentiates a complex multilineage tissue that possesses epithelium, a mesenchymal/stromal layer that includes organized smooth muscle, endothelial cells and enteric neurons. This is the first complex HIO model from iPSCs to spontaneously co-differentiate tissues from all 3 embryonic germ layers, which is a prerequisite for a fully formed and functional organ, and the phenotype is driven by specific members of the EGF-family of grow factors that are supplied as niche factors in the HIO growth medium. The goals of this proposal is to interrogate the development of the complex lineages present in complex HIOs (Aim 1), to further enhance the organization and complexity of HIOs by using a novel suspension culture method and via in vivo transplantation (Aim 2), and to functionally interrogate the vascular and neuronal cells present complex HIOs using microfluidics and in vivo transplantation (Aim 3).


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $527,060 )
2026	2026	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	1/27/2026	NON-COMPETING CONTINUATION	$527,060
														Subtotal = $527,060

Issue Date FY: 2025 ( Subtotal = $475,115 )
2025	2025	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE STE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	2/28/2025	NON-COMPETING CONTINUATION	$475,115
														Subtotal = $475,115

Issue Date FY: 2024 ( Subtotal = $542,726 )
2024	2024	REGENTS OF THE UNIVERSITY OF MICHIGAN	1109 GEDDES AVE, SUITE 3300	ANN ARBOR	MI	48109	WASHTENAW	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	2/19/2024	NEW	$542,726
														Subtotal = $542,726

Grand Total All Awards = $1,544,901

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Human iPSC intestine mimetics with integrated mesenchymal, endothelial and enteric nervous tissue

Award Number: R01DK137806

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2024

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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