Sdf-1 (CXCL12) induces CD9 expression in stem cells engaged in muscle regeneration

Brzóska, Edyta; Kowalski, Kamil; Markowska-Zagrajek, Agnieszka; Kowalewska, Magdalena; Archacki, Rafał; Plaskota, Izabela; Stremińska, Władysława; Jańczyk-Ilach, Katarzyna; Ciemerych, Maria A.

doi:10.1186/s13287-015-0041-1

Cited by 33 publications

(42 citation statements)

References 67 publications

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“…By silencing each of these receptors we were able to distinguish which one is involved in the regulation of certain genes. Thus, in ESCs expression of CD9 is regulated via Sdf-1 activating Cxcr4, but not Cxcr7, what was in agreement with our previous results documenting Sdf-1 dependent expression of CD9 in C2C12 myoblasts, bone marrow derived MSC, and ESCs 24 . Here we showed that also expression of ADAM9 is induced in ESCs by Sdf-1 in Cxcr4 dependent manner.…”

Section: Discussionsupporting

confidence: 93%

“…In our hands the pre-treatment of ESCs with Sdf-1 or co-injection of ESCs and Sdf-1 into skeletal muscles increased their ability to migrate within the regenerating tissue. Previously, we showed that ESCs pretreatment improved the ability of ESCs to migrate and fuse with myoblasts in vitro 24 . Since, Sdf-1 increased the expression of CD9 in ESCs we postulated that it might facilitate the fusion 24 .…”

Section: Discussionmentioning

confidence: 91%

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Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis

Kowalski

Kołodziejczyk

Sikorska

et al. 2016

Cell Adhesion & Migration

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The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor −1) increased migration of stem cells and their fusion with myoblasts in vitro. Importantly, we identified that Sdf-1 caused an increase in the expression of tetraspanin CD9 - adhesion protein involved in myoblasts fusion. In the current study we aimed to uncover the details of molecular mechanism of Sdf-1 action. We focused at the Sdf-1 receptors - Cxcr4 and Cxcr7, as well as signaling pathways induced by these molecules in primary myoblasts, as well as various stem cells - mesenchymal stem cells and embryonic stem cells, i.e. the cells of different migration and myogenic potential. We showed that Sdf-1 altered actin organization via FAK (focal adhesion kinase), Cdc42 (cell division control protein 42), and Rac-1 (Ras-Related C3 Botulinum Toxin Substrate 1). Moreover, we showed that Sdf-1 modified the transcription profile of genes encoding factors engaged in cells adhesion and migration. As the result, cells such as primary myoblasts or embryonic stem cells, became characterized by more effective migration when transplanted into regenerating muscle.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 91%

Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis

Kowalski

Kołodziejczyk

Sikorska

et al. 2016

Cell Adhesion & Migration

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“…In the present work, we focused on the bone marrow-derived cells (BMCs), which is the cell population that is isolated from bone marrow and contains the fraction of BM-MSCs. In our previous studies we showed that in-vitro cultured mouse CXCR4 + BMCs are able, with low frequency, to fuse with C2C12 myoblasts [ 40 ]. We also proved that stromal-derived factor-1 (Sdf-1) treatment led to increased tetraspanin CD9 expression facilitating CXCR4 + BMC fusion with C2C12 myoblasts [ 40 ].…”

Section: Introductionmentioning

confidence: 99%

“…In our previous studies we showed that in-vitro cultured mouse CXCR4 + BMCs are able, with low frequency, to fuse with C2C12 myoblasts [ 40 ]. We also proved that stromal-derived factor-1 (Sdf-1) treatment led to increased tetraspanin CD9 expression facilitating CXCR4 + BMC fusion with C2C12 myoblasts [ 40 ]. Currently, we have tested the myogenic potential of a BMC subpopulation that expresses CXCR4, a receptor for Sdf-1 which is the chemokine belonging to the cytokine family that plays an important role in stem cell mobilization [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Induction of bone marrow-derived cells myogenic identity by their interactions with the satellite cell niche

et al. 2018

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BackgroundSkeletal muscle regeneration is possible thanks to unipotent stem cells, which are satellite cells connected to the myofibers. Populations of stem cells other than muscle-specific satellite cells are considered as sources of cells able to support skeletal muscle reconstruction. Among these are bone marrow-derived mesenchymal stem cells (BM-MSCs), which are multipotent, self-renewing stem cells present in the bone marrow stroma. Available data documenting the ability of BM-MSCs to undergo myogenic differentiation are not definitive. In the current work, we aimed to check if the satellite cell niche could impact the ability of bone marrow-derived cells to follow a myogenic program.MethodsWe established a new in-vitro method for the coculture of bone marrow-derived cells (BMCs) that express CXCR4 (CXCR4+BMCs; the stromal-derived factor-1 (Sdf-1) receptor) with myofibers. Using various tests, we analyzed the myogenic identity of BMCs and their ability to fuse with myoblasts in vitro and in vivo.ResultsWe showed that Sdf-1 treatment increased the number of CXCR4+BMCs able to bind the myofiber and occupy the satellite cell niche. Moreover, interaction with myofibers induced the expression of myogenic regulatory factors (MRFs) in CXCR4+BMCs. CXCR4+BMCs, pretreated by the coculture with myofibers and Sdf-1, participated in myotube formation in vitro and also myofiber reconstruction in vivo. We also showed that Sdf-1 overexpression in vivo (in injured and regenerating muscles) supported the participation of CXCR4+BMCs in new myofiber formation.ConclusionWe showed that CXCR4+BMC interaction with myofibers (that is, within the satellite cell niche) induced CXCR4+BMC myogenic commitment. CXCR4+BMCs, pretreated using such a method of culture, were able to participate in skeletal muscle regeneration.

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“…Furthermore, cell recruitment is known to be important in the initial phase of fracture healing. The expression of CD9 on stem cells, including CD34 + hematopoietic stem cells, regulates migration, adhesion, and homing [44,45]. Thus, the retardation of fracture healing in CD9 2/2 mice might be related to impaired homing of stem and progenitor cells to the fracture site.…”

Section: /2mentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

Furuta

Miyaki

Ishitobi

et al. 2016

Stem Cells Translational Medicine

371

362

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Paracrine signaling by bone-marrow-derived mesenchymal stem cells (MSCs) plays a major role in tissue repair. Although the production of regulatory cytokines by MSC transplantation is a critical modulator of tissue regeneration, we focused on exosomes, which are extracellular vesicles that contain proteins and nucleic acids, as a novel additional modulator of cell-to-cell communication and tissue regeneration. To address this, we used radiologic imaging, histological examination, and immunohistochemical analysis to evaluate the role of exosomes isolated from MSC-conditioned medium (CM) in the healing process in a femur fracture model of CD9 2/2 mice, a strain that is known to produce reduced levels of exosomes. We found that the bone union rate in CD9 2/2 mice was significantly lower than wild-type mice because of the retardation of callus formation. The retardation of fracture healing in CD9 2/2 mice was rescued by the injection of exosomes, but this was not the case after the injection of exosomes-free conditioned medium (CM-Exo). The levels of the bone repairrelated cytokines, monocyte chemotactic protein-1 (MCP-1), MCP-3, and stromal cell-derived factor-1 in exosomes were low compared with levels in CM and CM-Exo, suggesting that bone repair may be in part mediated by other exosome components, such as microRNAs. These results suggest that exosomes in CM facilitate the acceleration of fracture healing, and we conclude that exosomes are a novel factor of MSC paracrine signaling with an important role in the tissue repair process. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1620-1630 SIGNIFICANCEThis work focuses on exosomes, which are extracellular vesicles, as a novel additional modulator of cell-to-cell communication. This study evaluated the role of exosomes isolated from mesenchymal stem cell (MSC)-conditioned medium (MSC-CM) in the fracture-healing process of CD9 2/2 mice, a strain that is known to produce reduced levels of exosomes. Retardation of fracture healing in CD9 2/2 mice was rescued by the injection of MSC exosomes, but this was not the case after the injection of exosome-free CM. This study finds that MSC exosomes are a novel factor of MSC paracrine signaling, with an important role in the tissue repair process.

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Sdf-1 (CXCL12) induces CD9 expression in stem cells engaged in muscle regeneration

Cited by 33 publications

References 67 publications

Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis

Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis

Induction of bone marrow-derived cells myogenic identity by their interactions with the satellite cell niche

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

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