Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2015; 7(8): 1127-1136
Published online Sep 26, 2015. doi: 10.4252/wjsc.v7.i8.1127
Autologous tissue patch rich in stem cells created in the subcutaneous tissue
Ignacio Garcia-Gomez, Krishnamurthy P Gudehithlu, Jose A L Arruda, Ashok K Singh
Ignacio Garcia-Gomez, Jose A L Arruda, Ashok K Singh, Division of Nephrology, Hektoen Institute of Medicine, Chicago, IL 60612, United States
Krishnamurthy P Gudehithlu, Jose A L Arruda, Ashok K Singh, John H. Stroger, Jr. Hospital of Cook County, Chicago, IL 60612, United States
Jose A L Arruda, Ashok K Singh, Division of Nephrology, Department of Medicine, University of Illinois Medical Center at Chicago and the Chicago VA Medical Center, Chicago, IL 60612, United States
Author contributions: Garcia-Gomez I and Singh AK performed experiments, interpreted data, and drafted the manuscript; Gudehithlu KP provided important technical help in designing the foreign body implants; Arruda JAL critically interpreted data and reviewed the manuscript.
Institutional animal care and use committee statement: All the animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of the John H. Stroger, Jr. Hospital of Cook County.
Conflict-of-interest statement: None.
Data sharing statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ashok K Singh, PhD, John H. Stroger, Jr. Hospital of Cook County, 1969 West Ogden Avenue, Chicago, IL 60612, United States. singhashok100@yahoo.com
Telephone: +1-312-8644613 Fax: +1-312-8649569
Received: November 26, 2014
Peer-review started: November 29, 2014
First decision: December 26, 2014
Revised: June 25, 2015
Accepted: July 16, 2015
Article in press: July 17, 2015
Published online: September 26, 2015
Processing time: 303 Days and 13.6 Hours
Abstract

AIM: To investigate whether we could create natural autologous tissue patches in the subcutaneous space for organ repair.

METHODS: We implanted the following three types of inert foreign bodies in the subcutaneous tissue of rats to produce autologous tissue patches of different geometries: (1) a large-sized polyvinyl tube (L = 25 mm, internal diameter = 7 mm) sealed at both ends by heat application for obtaining a large flat piece of tissue patch for organ repair; (2) a fine polyvinyl tubing (L = 25 mm, internal diameter = 3 mm) for creating cylindrically shaped grafts for vascular or nerve repair; and (3) a slurry of polydextran particle gel for inducing a bladder-like tissue. Implantation of inert materials was carried out by making a small incision on one or either side of the thoracic-lumbar region of rats. Subcutaneous pockets were created by blunt dissection around the incision into which the inert bodies were inserted (1 or 2 per rat). The incisions were closed with silk sutures, and the animals were allowed to recover. In case of the polydextran gel slurry 5 mL of the slurry was injected in the subcutaneous space using an 18 gauge needle. After implanting the foreign bodies a newly regenerated encapsulating tissue developed around the foreign bodies. The tissues were harvested after 4-42 d of implantation and studied by gross examination, histology, and histochemistry for organization, vascularity, and presence of mesenchymal stem cells (MSCs) (CD271+CD34+ cells).

RESULTS: Implanting a large cylindrically shaped polyvinyl tube resulted in a large flat sheet of tissue that could be tailored to a specific size and shape for use as a tissue patch for repairing large organs. Implanting a smaller sized polyvinyl tube yielded a cylindrical tissue that could be useful for repairing nerves and blood vessels. This type of patch could be obtained in different lengths by varying the length of the implanted tube. Implanting a suspension of inert polydextran suspension gave rise to a bladder-like tissue that could be potentially used for repairing heart valves. Histologically, the three different types of tissue patches generated were organized similarly, consisting of three layers, increasing in thickness until day 14. The inner layer in contact with the inert material was avascular; a middle layer that was highly vascular and filled with matrix, and an outer layer consisting of loose connective tissue. MSCs identified as CD271+CD34+ cells were present in the medial layer and around major blood vessels at day 4 but absent at later time points. The early-harvested tissues, endowed with MSCs, could be used for tissue repair, while the later-harvested tissues, being less vascular but thicker and tougher, could be used as filler tissue for cosmetic purposes.

CONCLUSION: An autologous, vascularized tissue patch of desired shape and size can be created in the subcutaneous space by implanting different types of inert bodies.

Keywords: Autologous tissue patch; Foreign body; Subcutaneous implantation; Mesenchymal stem cells; CD271; CD34

Core tip: While much progress has been made in man-made tissue patches for organ repair, their clinical success has been bogged down by their inability to get promptly vascularized in vivo. We describe a methodology for creating tissue patches of several possible shapes/sizes in the subcutaneous tissue utilizing the foreign body reaction. These patches are endowed with a rich capillary network, abundant mesenchymal stem cells, and other accessory cells that support the viability of the tissue. Such in vivo generated patches for tissue repair promise to be safer, more readily vascularized, and stable for longer period in the body.