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Recellularization of acellular human small intestine using bone marrow stem cells.

Journal article
Authors Pradeep B Patil
Priti Chougule
Vijay Kumar Kuna
Stefan Almström
Henrik Bäckdahl
Debashish Banerjee
Gustaf Herlenius
Michael Olausson
Suchitra Sumitran-Holgersson
Published in Stem cells translational medicine
Volume 2
Issue 4
Pages 307-15
ISSN 2157-6564
Publication year 2013
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Biomedicine
Pages 307-15
Language en
Links dx.doi.org/10.5966/sctm.2012-0108
Keywords Adult human bone marrow, Adult stem cells, Transdifferentiation, Differentiation
Subject categories Transplantation surgery

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.

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