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Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts
- Source :
- Nature Communications, Vol 8, Iss 1, Pp 1-13 (2017), Kitano, K; Schwartz, DM; Zhou, H; Gilpin, SE; Wojtkiewicz, GR; Ren, X; et al.(2017). Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts. Nature Communications, 8(1). doi: 10.1038/s41467-017-00779-y. UC Berkeley: Retrieved from: http://www.escholarship.org/uc/item/7811z3rj, Nature Communications
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Patients with short bowel syndrome lack sufficient functional intestine to sustain themselves with enteral intake alone. Transplantable vascularized bioengineered intestine could restore nutrient absorption. Here we report the engineering of humanized intestinal grafts by repopulating decellularized rat intestinal matrix with human induced pluripotent stem cell-derived intestinal epithelium and human endothelium. After 28 days of in vitro culture, hiPSC-derived progenitor cells differentiate into a monolayer of polarized intestinal epithelium. Human endothelial cells seeded via native vasculature restore perfusability. Ex vivo isolated perfusion testing confirms transfer of glucose and medium-chain fatty acids from lumen to venous effluent. Four weeks after transplantation to RNU rats, grafts show survival and maturation of regenerated epithelium. Systemic venous sampling and positron emission tomography confirm uptake of glucose and fatty acids in vivo. Bioengineering intestine on vascularized native scaffolds could bridge the gap between cell/tissue-scale regeneration and whole organ-scale technology needed to treat intestinal failure patients.<br />There is a need for humanised grafts to treat patients with intestinal failure. Here, the authors generate intestinal grafts by recellularizing native intestinal matrix with human induced pluripotent stem cell-derived epithelium and human endothelium, and show nutrient absorption after transplantation in rats.
- Subjects :
- Male
Short Bowel Syndrome
0301 basic medicine
Pathology
medicine.medical_specialty
Endothelium
Science
Induced Pluripotent Stem Cells
Transplants
General Physics and Astronomy
Bioengineering
Article
General Biochemistry, Genetics and Molecular Biology
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Intestinal mucosa
medicine
Animals
Humans
Intestinal Mucosa
Progenitor cell
Induced pluripotent stem cell
lcsh:Science
Cells, Cultured
Cell Proliferation
Multidisciplinary
Tissue Engineering
Tissue Scaffolds
business.industry
Fatty Acids
Endothelial Cells
Cell Differentiation
General Chemistry
Intestinal epithelium
Epithelium
Small intestine
Rats
3. Good health
Intestines
Transplantation
Glucose
030104 developmental biology
medicine.anatomical_structure
surgical procedures, operative
030220 oncology & carcinogenesis
lcsh:Q
business
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....ccbe321a332ea16d6e56f9da1fdc2c3f