Immunoselection and adenoviral genetic modulation of human osteoprogenitors: in vivo bone formation on PLA scaffold
Immunoselection and adenoviral genetic modulation of human osteoprogenitors: in vivo bone formation on PLA scaffold
The aim of this study was to examine the potential of immunoselected genetically modified human osteoprogenitors to form bone in vivo on porous PLA scaffolds. Human osteoprogenitors from bone marrow were selected using the antibody STRO-1 utilising a magnetically activated cell separation system. The STRO-1+ fraction isolated 7% of nucleated marrow cells and increased fibroblastic colony formation by 300% and alkaline phosphatase activity by 190% over unselected marrow cell cultures. To engineer bone tissue, STRO-1+ culture-expanded cells were transduced with AxCAOBMP-2, an adenovirus carrying the human BMP-2 gene, injected into diffusion chambers containing porous PLA scaffolds, and implanted in vivo. After 11 weeks the presence of bone mineral was observed by X-ray analysis and confirmed for mineral by von Kossa, as well as bone matrix composition by Sirius red staining, birefringence, and type I collagen immunohistochemistry. Bone formation in vivo indicates the potential of using immunoselected progenitor cells and ex vivo gene transfer with biodegradable scaffolds, for the development of protocols for the treatment of a wide variety of musculo-skeletal disorders.
osteoprogenitor, mesenchymal stem cell, immunoselection, stro-1 monoclonal antibody, adenoviral gene-transfer, bone morphogenetic protein-2, biodegradable polymer, poly(d, l-lactic acid), tissue engineering
208-215
Howard, Daniel
40caa4c6-e523-4674-8973-992f2b1c5583
Partridge, Kris
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Yang, Xuebin
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Clarke, Nicholas M.P.
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Okubo, Yasunori
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Bessho, Kazuhisa
a688a281-3233-40c0-b9e7-296a64f57fad
Howdle, Steven M.
ec70f53e-a5df-4e99-9da2-f90582dde80b
Shakesheff, Kevin M.
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Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
2002
Howard, Daniel
40caa4c6-e523-4674-8973-992f2b1c5583
Partridge, Kris
64fd1f95-bf24-4251-ad6e-4c96068b7fc5
Yang, Xuebin
3030c19f-22e3-4dc6-9c12-dbcc66ceb694
Clarke, Nicholas M.P.
76688c21-d51e-48fa-a84d-deec66baf8ac
Okubo, Yasunori
0ccceeb5-9076-46c0-8bbc-fae8514dfd12
Bessho, Kazuhisa
a688a281-3233-40c0-b9e7-296a64f57fad
Howdle, Steven M.
ec70f53e-a5df-4e99-9da2-f90582dde80b
Shakesheff, Kevin M.
5b9ed879-e2c5-4c62-bb38-abd2bb4960ac
Oreffo, Richard O.C.
ff9fff72-6855-4d0f-bfb2-311d0e8f3778
Howard, Daniel, Partridge, Kris, Yang, Xuebin, Clarke, Nicholas M.P., Okubo, Yasunori, Bessho, Kazuhisa, Howdle, Steven M., Shakesheff, Kevin M. and Oreffo, Richard O.C.
(2002)
Immunoselection and adenoviral genetic modulation of human osteoprogenitors: in vivo bone formation on PLA scaffold.
Biochemical and Biophysical Research Communications, 299 (2), .
(doi:10.1016/S0006-291X(02)02561-5).
Abstract
The aim of this study was to examine the potential of immunoselected genetically modified human osteoprogenitors to form bone in vivo on porous PLA scaffolds. Human osteoprogenitors from bone marrow were selected using the antibody STRO-1 utilising a magnetically activated cell separation system. The STRO-1+ fraction isolated 7% of nucleated marrow cells and increased fibroblastic colony formation by 300% and alkaline phosphatase activity by 190% over unselected marrow cell cultures. To engineer bone tissue, STRO-1+ culture-expanded cells were transduced with AxCAOBMP-2, an adenovirus carrying the human BMP-2 gene, injected into diffusion chambers containing porous PLA scaffolds, and implanted in vivo. After 11 weeks the presence of bone mineral was observed by X-ray analysis and confirmed for mineral by von Kossa, as well as bone matrix composition by Sirius red staining, birefringence, and type I collagen immunohistochemistry. Bone formation in vivo indicates the potential of using immunoselected progenitor cells and ex vivo gene transfer with biodegradable scaffolds, for the development of protocols for the treatment of a wide variety of musculo-skeletal disorders.
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More information
Published date: 2002
Keywords:
osteoprogenitor, mesenchymal stem cell, immunoselection, stro-1 monoclonal antibody, adenoviral gene-transfer, bone morphogenetic protein-2, biodegradable polymer, poly(d, l-lactic acid), tissue engineering
Identifiers
Local EPrints ID: 25643
URI: http://eprints.soton.ac.uk/id/eprint/25643
ISSN: 0006-291X
PURE UUID: 56a68492-53ca-4fcc-88db-33fda56b3a47
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Date deposited: 11 Apr 2006
Last modified: 16 Mar 2024 03:11
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Contributors
Author:
Daniel Howard
Author:
Kris Partridge
Author:
Xuebin Yang
Author:
Yasunori Okubo
Author:
Kazuhisa Bessho
Author:
Steven M. Howdle
Author:
Kevin M. Shakesheff
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