Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation
<p>Abstract</p> <p>Background</p> <p>Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. In murine-to-murine transplantation experiments, CXCR4 expression marks a population of adult murine satellite cells with rob...
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Format: | Article |
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BMC
2012-02-01
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Series: | Skeletal Muscle |
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Online Access: | http://www.skeletalmusclejournal.com/content/2/1/4 |
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author | Parker Maura H Loretz Carol Tyler Ashlee E Snider Lauren Storb Rainer Tapscott Stephen J |
author_facet | Parker Maura H Loretz Carol Tyler Ashlee E Snider Lauren Storb Rainer Tapscott Stephen J |
author_sort | Parker Maura H |
collection | DOAJ |
description | <p>Abstract</p> <p>Background</p> <p>Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. In murine-to-murine transplantation experiments, CXCR4 expression marks a population of adult murine satellite cells with robust engraftment potential in <it>mdx </it>mice, and CXCR4-positive murine muscle-derived SP cells home more effectively to dystrophic muscle after intra-arterial delivery in <it>mdx<sup>5cv </sup></it>mice. Together, these data suggest that CXCR4 plays an important role in donor cell engraftment. Therefore, we sought to translate these results to a clinically relevant canine-to-canine allogeneic transplant model for Duchenne muscular dystrophy (DMD) and determine if CXCR4 is important for donor cell engraftment.</p> <p>Methods</p> <p>In this study, we used a canine-to-murine xenotransplantation model to quantitatively compare canine muscle cell engraftment, and test the most effective cell population and modulating factor in a canine model of DMD using allogeneic transplantation experiments.</p> <p>Results</p> <p>We show that CXCR4 expressing cells are important for donor muscle cell engraftment, yet FACS sorted CXCR4-positive cells display decreased engraftment efficiency. However, diprotin A, a positive modulator of CXCR4-SDF-1 binding, significantly enhanced engraftment and stimulated sustained proliferation of donor cells <it>in vivo</it>. Furthermore, the canine-to-murine xenotransplantation model accurately predicted results in canine-to-canine muscle cell transplantation.</p> <p>Conclusions</p> <p>Therefore, these results establish the efficacy of diprotin A in stimulating muscle cell engraftment, and highlight the pre-clinical utility of a xenotransplantation model in assessing the relative efficacy of muscle stem cell populations.</p> |
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issn | 2044-5040 |
language | English |
last_indexed | 2024-12-10T11:45:00Z |
publishDate | 2012-02-01 |
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series | Skeletal Muscle |
spelling | doaj.art-f7dd2823c0ed4f75bfd3c0205297e5792022-12-22T01:50:07ZengBMCSkeletal Muscle2044-50402012-02-0121410.1186/2044-5040-2-4Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferationParker Maura HLoretz CarolTyler Ashlee ESnider LaurenStorb RainerTapscott Stephen J<p>Abstract</p> <p>Background</p> <p>Transplantation of myogenic stem cells possesses great potential for long-term repair of dystrophic muscle. In murine-to-murine transplantation experiments, CXCR4 expression marks a population of adult murine satellite cells with robust engraftment potential in <it>mdx </it>mice, and CXCR4-positive murine muscle-derived SP cells home more effectively to dystrophic muscle after intra-arterial delivery in <it>mdx<sup>5cv </sup></it>mice. Together, these data suggest that CXCR4 plays an important role in donor cell engraftment. Therefore, we sought to translate these results to a clinically relevant canine-to-canine allogeneic transplant model for Duchenne muscular dystrophy (DMD) and determine if CXCR4 is important for donor cell engraftment.</p> <p>Methods</p> <p>In this study, we used a canine-to-murine xenotransplantation model to quantitatively compare canine muscle cell engraftment, and test the most effective cell population and modulating factor in a canine model of DMD using allogeneic transplantation experiments.</p> <p>Results</p> <p>We show that CXCR4 expressing cells are important for donor muscle cell engraftment, yet FACS sorted CXCR4-positive cells display decreased engraftment efficiency. However, diprotin A, a positive modulator of CXCR4-SDF-1 binding, significantly enhanced engraftment and stimulated sustained proliferation of donor cells <it>in vivo</it>. Furthermore, the canine-to-murine xenotransplantation model accurately predicted results in canine-to-canine muscle cell transplantation.</p> <p>Conclusions</p> <p>Therefore, these results establish the efficacy of diprotin A in stimulating muscle cell engraftment, and highlight the pre-clinical utility of a xenotransplantation model in assessing the relative efficacy of muscle stem cell populations.</p>http://www.skeletalmusclejournal.com/content/2/1/4muscular dystrophycell transplantationxenotransplantcanineCXCR4diprotin A |
spellingShingle | Parker Maura H Loretz Carol Tyler Ashlee E Snider Lauren Storb Rainer Tapscott Stephen J Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation Skeletal Muscle muscular dystrophy cell transplantation xenotransplant canine CXCR4 diprotin A |
title | Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation |
title_full | Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation |
title_fullStr | Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation |
title_full_unstemmed | Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation |
title_short | Inhibition of CD26/DPP-IV enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation |
title_sort | inhibition of cd26 dpp iv enhances donor muscle cell engraftment and stimulates sustained donor cell proliferation |
topic | muscular dystrophy cell transplantation xenotransplant canine CXCR4 diprotin A |
url | http://www.skeletalmusclejournal.com/content/2/1/4 |
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