Direct Isolation of Satellite Cells for Skeletal Muscle Regeneration

Montarras, Didier; Morgan, Jennifer E.; Collins, Charlotte; Relaix, Frédéric; Zaffran, Stéphane; Cumano, Ana; Partridge, Terence A.; Buckingham, Margaret

doi:10.1126/science.1114758

Cited by 940 publications

(1,021 citation statements)

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“…Encouraging results have been obtained following the transplantation of several stem cell preparations [29,[41][42][43][44][45][46][47][48] into mouse models of muscular dystrophy. Although most of these studies comprise cell populations isolated directly from muscle tissues, such as satellite cells and mesoangioblasts, stromal cells from bone marrow [29] and adipose tissues [46,47] have also been attributed with in vivo muscle regenerative potential.…”

Section: Discussionmentioning

confidence: 99%

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

Gang

Darabi

Bosnakovski

et al. 2009

Experimental Cell Research

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Mesenchymal stem cell preparations have been proposed for muscle regeneration in musculoskeletal disorders. Although MSCs have great in vitro expansion potential and possess the ability to differentiate into several mesenchymal lineages, myogenesis has proven to be much more difficult to induce. We have recently demonstrated that Pax3, the master regulator of the embryonic myogenic program, enables the in vitro differentiation of a murine mesenchymal stem cell line (MSCB9-Pax3) into myogenic progenitors. Here we show that injection of these cells into cardiotoxin-injured muscles of immunodeficient mice leads to the development of muscle tumors, resembling rhabdomyosarcomas. We then extended these studies to primary human mesenchymal stem cells (hMSCs) isolated from bone marrow. Upon genetic modification with a lentiviral vector encoding PAX3, hMSCs activated the myogenic program as demonstrated by expression of myogenic regulatory factors. Upon transplantation, the PAX3-modified MSCs did not generate rhabdomyosarcomas but rather, resulted in donor-derived myofibers. These were found at higher frequency in PAX3-transduced hMSCs than in mock-transduced MSCs. Nonetheless, neither engraftment of PAX3-modified or unmodified MSCs resulted in improved contractility.Thus these findings suggest that limitations remain to be overcome before MSC preparations result in effective treatment for muscular dystrophies.

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Section: Discussionmentioning

confidence: 99%

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

Gang

Darabi

Bosnakovski

et al. 2009

Experimental Cell Research

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“…Leur capacité à assurer à la fois le renouvellement continu des noyaux des fibres musculaires et la régénération musculaire suggère l'existence de mécanismes qui permettent de maintenir un réservoir de cellules satellites tout au long de la vie [2]. In vivo, la preuve de l'autorenouvellement des cellules satellites a été obtenue après greffe de fibres isolées [3] ou de populations de cellules satellites quiescentes [4]. Des études ex vivo faites sur des fibres isolées qui étaient en phase de prolifération ont montré qu'un petit nombre des cellules précurseurs myogéniques (mpc) issues de la division des cellules satellites ne s'engagent pas dans la différenciation terminale mais constituent une réserve des cellules progénitrices sans qu'on puisse, dans ces conditions expérimen-tales de manipulation de fibres isolées, les nommer cellules satellites [5].…”

Section: Magazineunclassified

“…Cette sécrétion paracrine locale d'Ang1 s'ajoute donc à la sécrétion autocrine par les cellules de réserve elles-mêmes. Ensuite, nous avons confirmé cette relation entre degré d'immaturité, quiescence et contrôle par Ang1/Tie-2 en analysant les cellules satellites isolées de différentes lignées murines généti-quement modifiées : les souris transgéniques Tie-2-GFP (green fluorescent protein) ; les souris Pax3/GFP chez lesquelles on peut isoler des cellules satellites quiescentes chez l'adulte et non quiescentes chez le jeune [4] ; les souris Myf5-Cre*ROSA-YFP qui permettent d'isoler des populations de cellules satellites Myf5/YFP -et Myf5/YFP + , les premières s'autorenouvelant 4 fois plus que les secondes [6]. L'analyse des populations satellites obtenues après tri cellulaire à partir de ces différen-tes souches de souris, montre que in vivo, plus les cellules satellites sont quiescentes, plus elles expriment Tie-2.…”

Section: Ang1 Un Intermédiaire Crucial Présent Dans L'environnement unclassified

Les cellules du muscle chantent en chœur une berceuse pour cellules souches

Abou-Khalil

Partridge

Chazaud³

2010

Med Sci (Paris)

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“…The cell isolation protocol was adopted from Montarras et al [39] and CD34 þve cell selection was performed using a magnetic EasySep-PE Cell Separation Kit (Stem Cell Technologies, Vancouver, BC, Canada, http://www.stemcell.com) according to the manufacturer's instructions with anti-CD34 biotinylated antibody (eBioscience Inc., San Diego, CA, http://www.ebioscience.com; 1:50).…”

Section: Isolation Of Donor Cd34 1ve Cellsmentioning

confidence: 99%

Methylguanine DNA Methyltransferase-Mediated Drug Resistance-Based Selective Enrichment and Engraftment of Transplanted Stem Cells in Skeletal Muscle

et al. 2009

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Cell replacement therapy using stem cell transplantation holds much promise in the field of regenerative medicine. In the area of hematopoietic stem cell transplantation, O 6 -methylguanine-DNA methyltransferase MGMT (P140K) gene-mediated drug resistance-based in vivo enrichment strategy of donor stem cells has been shown to achieve up to 75%-100% donor cell engraftment in the host's hematopoietic stem cell compartment following repeated rounds of selection. This strategy, however, has not been applied in any other organ system. We tested the feasibility of using this MGMT (P140K)-mediated enrichment strategy for cell transplantation in skeletal muscles of mice. We demonstrate that muscle cells expressing an MGMT (P140K) drug resistance gene can be protected and selectively enriched in response to alkylating chemotherapy both in vitro and in vivo. Upon transplantation of MGMT (P140K)-expressing male CD34 1ve donor stem cells isolated from regenerating skeletal muscle into injured female muscle treated with alkylating chemotherapy, donor cells showed enhanced engraftment in the recipient muscle 7 days following transplantation as examined by quantitative-polymerase chain reaction using Y-chromosome specific primers. Fluorescent in situ hybridization analysis using a Y-chromosome paint probe revealed donor-derived de novo muscle fiber formation in the recipient muscle 14 days following transplantation, with approximately 12.5% of total nuclei within the regenerated recipient muscle being of donor origin. Following engraftment, the chemo-protected donor CD34 1ve cells induced substantial endogenous regeneration of the chemo-ablated host muscle that is otherwise unable to selfregenerate. We conclude that the MGMT (P140K)-mediated enrichment strategy can be successfully implemented in muscle.

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Direct Isolation of Satellite Cells for Skeletal Muscle Regeneration

Cited by 940 publications

References 24 publications

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

Les cellules du muscle chantent en chœur une berceuse pour cellules souches

Methylguanine DNA Methyltransferase-Mediated Drug Resistance-Based Selective Enrichment and Engraftment of Transplanted Stem Cells in Skeletal Muscle

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