title: Recellularization of acellular human small intestine using bone marrow stem cells.
abstract: We aimed to produce an acellular human tissue scaffold with a view to test the possibility of recellularization with bone marrow stem cells to produce a tissue-engineered small intestine (TESI). Human small-bowel specimens (n = 5) were obtained from cadaveric organ donors and treated sequentially with 6% dimethyl sulfoxide in hypotonic buffer, 1% Triton X-100, and DNase. Each small intestine (SI) piece (6 cm) was recellularized with EPCAM+ and CD133+ allogeneic bone marrow stem cells. Histological and molecular analysis demonstrated that after decellularization, all cellular components and nuclear material were removed. Our analysis also showed that the decellularized human SI tissue retained its histoarchitecture with intact villi and major structural proteins. Protein films of common extracellular matrix constituents (collagen I, laminin, and fibronectin) were found in abundance. Furthermore, several residual angiogenic factors were found in the decellularized SI. Following recellularization, we found viable mucin-positive goblet cells, CK18+ epithelial cells in villi adjacent to a muscularis mucosa with α-actin+ smooth muscle cells, and a high repopulation of blood vessels with CD31+ endothelial cells. Our results show that in the future, such a TESI would be ideal for clinical purposes, because it can be derived from the recipient's own immunocompatible bone marrow cells, thus avoiding the use of immunosuppression.
authors.affiliation: Laboratory for Transplantation and Regenerative Medicine, Department of Surgery, University of Gothenburg, Sweden.
authors.forename: Pradeep B
authors.initials: PB
authors.lastname: Patil
authors.forename: Priti B
authors.initials: PB
authors.lastname: Chougule
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Kumar
authors.forename: Stefan
authors.initials: S
authors.lastname: Almström
authors.forename: Henrik
authors.initials: H
authors.lastname: Bäckdahl
authors.forename: Debashish
authors.initials: D
authors.lastname: Banerjee
authors.forename: Gustaf
authors.initials: G
authors.lastname: Herlenius
authors.forename: Michael
authors.initials: M
authors.lastname: Olausson
authors.forename: Suchitra
authors.initials: S
authors.lastname: Sumitran-Holgersson
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D001696:Biomechanical Phenomena; D001854:Bone Marrow Cells / Q000166:cytology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002452:Cell Count; D048430:Cell Shape; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D000071858:Epithelial Cell Adhesion Molecule; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007421:Intestine, Small / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D013194:Staining and Labeling; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000606023:PROM1 protein, human; D010455:Peptides