The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries

Kobayashi, Makoto; Ota, Satoshi; Terada, Satoshi; Kawakami, Yoshiyuki; Otsuka, Takanobu; Fu, Freddie H.; Huard, Johnny

doi:10.1177/0363546516656823

Cited by 53 publications

(47 citation statements)

References 56 publications

(82 reference statements)

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“…Complete healing following muscle injury has been the focus of many recent investigations, including approaches to alter the inflammatory cascade [21,22] and introduction of stem cell therapy [12,23,24]. This study provides a novel method of inducing injury that is mechanistically relevant to the eccentric or strain injuries seen clinically [19].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Improve Muscle Function Following Single Stretch Injury: A Preliminary Study

Brickson

Meyer

Saether

et al. 2016

JFMK

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Abstract:Stem cells have shown promise as a therapeutic intervention by enhancing skeletal muscle regeneration following muscle injury. The purpose of this study was to determine the effect of mouse mesenchymal stem cells (MSCs) on muscle function following a single stretch injury in the calf muscle of C57BL/67 mice. A custom isokinetic device was used to induce a single stretch injury. An intramuscular injection of MSCs or saline was administered three days post-injury. Mechanical testing to measure peak isometric joint torque in vivo was done immediately and at seven or 14 days post-injury. Susceptibility to reinjury was assessed in the soleus muscle using an in situ repeated eccentric contraction (ECC) protocol. In vivo isometric torque of the plantar flexors dropped immediately following stretch injury by 50%. Treatment with MSCs attenuated the torque deficit at seven days, while there were no differences in torque deficit between groups at 14 days. In situ ECC testing of the soleus showed a significant specific force drop following injury, with the MSC group demonstrating a protective effect at seven and 14 days. These results demonstrate transient improvement in isometric torque and reduced susceptibility to reinjury following single stretch injury with intramuscular injection of MSCs.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells Improve Muscle Function Following Single Stretch Injury: A Preliminary Study

Brickson

Meyer

Saether

et al. 2016

JFMK

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“…What we need to do now is to pay attention to the expression level of TGF‐β1 in scar‐free repair wounds, and to the temporal and spatial dynamics of TGF‐β1 to control the homeostasis of reepithelialisation, vascularization, and inflammation . In fact, there are various means of regulating the TGF‐β1 signalling pathway, including antibodies, antagonists, and even miRNA means . However, using antagonists of TGF‐β1 receptors or TGF‐β1 specific antibodies could merely reach clinical request due to the safety accidents .…”

Section: Biotherapy Aimed At Main Cytokines and Protein Involved In Hssmentioning

confidence: 99%

“…152,153 In fact, there are various means of regulating the TGF-β1 signalling pathway, including antibodies, antagonists, and even miRNA means. [154][155][156][157][158] However, using antagonists of TGF-β1 receptors or TGF-β1 specific antibodies could merely reach clinical request due to the safety accidents. 159,160 Hence, targeting to the modulation of TGF-β1 or its downstream pathway may be more feasible.…”

Section: Biotherapy Aimed At Main Cytokines and Protein Involved Inmentioning

confidence: 99%

Biological approaches for hypertrophic scars

Zhong

2019

International Wound Journal

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Scar formation is usually the pathological consequence of skin trauma. And hypertrophic scars (HSs) frequently occur in people after being injured deeply. HSs are unusually considered as the result of tissue contraction and excessive extracellular matrix component deposition. Myofibroblasts, as the effector cells, mainly differentiated from fibroblasts, play the crucial role in the pathophysiology of HSs. A number of growth factors, inflammatory cytokines involved in the process of HS occurrence. Currently, with in‐depth exploration and clinical research of HSs, various creative and effective treatments budded. In here, we summarize the progress in the molecular mechanism of HSs, and review the available biotherapeutic methods for their pathophysiological characteristics. Additionally, we further prospected that the comprehensive therapy may be more suitable for HS treatment.

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“…Transplantation of MDSCs into injured skeletal muscle led to improved muscle healing after injury through the promotion of angiogenesis, which consequently decreased fibrosis . More recently, we found combined use of anti‐fibrotic agents along with MDSC transplantation further improved skeletal muscle healing compared to each treatment individually, since MDSCs can differentiate into fibrotic cells and the anti‐fibrotic agent reduced that differentiation pathway …”

Section: Isolation and Characterization Of Mdscsmentioning

confidence: 99%

“…27 More recently, we found combined use of anti-fibrotic agents along with MDSC transplantation further improved skeletal muscle healing compared to each treatment individually, since MDSCs can differentiate into fibrotic cells and the anti-fibrotic agent reduced that differentiation pathway. 28 Subsequently, we used MDSCs in a variety of regenerative medicine approaches to improve healing of numerous tissue types, including bone, articular cartilage (AC), peripheral nerves, and ligaments, [29][30][31][32][33][34][35][36] as well as non-musculoskeletal tissues, including heart and bladder. In fact, these cells have already entered the clinical arena, where we have treated over 600 patients with stress urinary incontinence (Phase III trial) 37 and 12 myocardial infarction patients (Phase 1 trial).…”

Section: Role Of Angiogenesis In Stem Cell-mediated Skeletal Muscle Rmentioning

confidence: 99%

Stem cells, blood vessels, and angiogenesis as major determinants for musculoskeletal tissue repair

Huard

2018

Journal Orthopaedic Research

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This manuscript summarizes 20 years of research from my laboratories at the University of Pittsburgh and more recently, at the University of Texas Health Science Center at Houston and the Steadman Philippon Research Institute in Vail, Colorado. The discovery of muscle-derived stem cells (MDSCs) did not arise from a deliberate search to find a novel population of muscle cells with high regenerative potential, but instead was conceived in response to setbacks encountered while working in muscle cell transplantation for Duchenne muscular dystrophy (DMD). DMD is a devastating inherited X-linked muscle disease characterized by progressive muscle weakness due to lack of dystrophin expression in muscle fiber sarcolemma. Although the transplantation of normal myoblasts into dystrophin-deficient muscle can restore dystrophin, this approach has been hindered by limited survival (less than 1%) of the injected cells. The fact that 99% of the cells were not surviving implantation was seen as a major weakness with this technology by most. My research team decided to investigate which cells represent the 1% of the cells surviving post-implantation. We have subsequently confirmed that the few cells which exhibit high survival post-implantation also display stem cell characteristics, and were termed "muscle-derived stem cells" or MDSCs. Herein, I will describe the origin of these MDSCs, the mechanisms of MDSC action during tissue repair, and finally the development of therapeutic strategies to improve regeneration and repair of musculoskeletal tissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-9, 2018.

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The Combined Use of Losartan and Muscle-Derived Stem Cells Significantly Improves the Functional Recovery of Muscle in a Young Mouse Model of Contusion Injuries

Abstract: The study findings contribute to the development of biological treatments to accelerate and improve the quality of muscle healing after injury.

Cited by 53 publications

References 56 publications

Mesenchymal Stem Cells Improve Muscle Function Following Single Stretch Injury: A Preliminary Study

Mesenchymal Stem Cells Improve Muscle Function Following Single Stretch Injury: A Preliminary Study

Biological approaches for hypertrophic scars

Stem cells, blood vessels, and angiogenesis as major determinants for musculoskeletal tissue repair

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