Mechanical regulation of mesenchymal stem cell differentiation

Steward, Andrew J.; Kelly, Daniel J.

doi:10.1111/joa.12243

Cited by 193 publications

(144 citation statements)

References 152 publications

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“…Multiple MSC niches have been described within various tissues (Figure 3) and stem cells housed in them isolated and utilized for chondrogenic repair. MSCs have been found in the bone marrow, adipose tissue, articular cartilage, synovium, skeletal muscle, dental pulp, circulatory system, heart, brain, umbilical cord tissues (including Wharton's jelly), and other connective tissues (Gronthos et al, 2000; Zuk et al, 2001; Alsalameh et al, 2004; Dowthwaite et al, 2004; Crisan et al, 2008; Gronthos and Zannettino, 2011; Batsali et al, 2013; Mobasheri et al, 2014; Steward and Kelly, 2015). …”

Section: Tissue Reservoirs Of Mscsmentioning

confidence: 99%

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

et al. 2016

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Current cell-based repair strategies have proven unsuccessful for treating cartilage defects and osteoarthritic lesions, consequently advances in innovative therapeutics are required and mesenchymal stem cell-based (MSC) therapies are an expanding area of investigation. MSCs are capable of differentiating into multiple cell lineages and exerting paracrine effects. Due to their easy isolation, expansion, and low immunogenicity, MSCs are an attractive option for regenerative medicine for joint repair. Recent studies have identified several MSC tissue reservoirs including in adipose tissue, bone marrow, cartilage, periosteum, and muscle. MSCs isolated from these discrete tissue niches exhibit distinct biological activities, and have enhanced regenerative potentials for different tissue types. Each MSC type has advantages and disadvantages for cartilage repair and their use in a clinical setting is a balance between expediency and effectiveness. In this review we explore the challenges associated with cartilage repair and regeneration using MSC-based cell therapies and provide an overview of phenotype, biological activities, and functional properties for each MSC population. This paper also specifically explores the therapeutic potential of each type of MSC, particularly focusing on which cells are capable of producing stratified hyaline-like articular cartilage regeneration. Finally we highlight areas for future investigation. Given that patients present with a variety of problems it is unlikely that cartilage regeneration will be a simple “one size fits all,” but more likely an array of solutions that need to be applied systematically to achieve regeneration of a biomechanically competent repair tissue.

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Section: Tissue Reservoirs Of Mscsmentioning

confidence: 99%

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

et al. 2016

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“…[3][4][5] ECM stiffness has been shown to induce actin cytoskeletal reorganization and contractility, thereby controlling adhesion, migration, cell cycle progression, and differentiation. [6][7][8] The translation of ECM stiffness into intracellular signals to change cell behavior is mainly mediated by transmembrane receptors, known as integrins. Integrins are heterodimers consisting of a¡ and b¡subunits with the b-subunit tail linking to the actin cytoskeleton through several different adaptor proteins.…”

Section: Molecular Regulation By Mechanical Stimulationmentioning

confidence: 99%

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

et al. 2015

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ABSTRACT. Tissue development is orchestrated by the coordinated activities of both chemical and physical regulators. While much attention has been given to the role that chemical regulators play in driving development, researchers have recently begun to elucidate the important role that the mechanical properties of the extracellular environment play. For instance, the stiffness of the extracellular environment has a role in orienting cell division, maintaining tissue boundaries, directing cell migration, and driving differentiation. In addition, extracellular matrix stiffness is important for maintaining normal tissue homeostasis, and when matrix mechanics become imbalanced, disease progression may ensue. In this article, we will review the important role that matrix stiffness plays in dictating cell behavior during development, tissue homeostasis, and disease progression.

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“…92 Differences are also observed mechanically, as softer substrates promote adipogenesis while stiffer substrates promote myogenesis. 93 These differences, and subsequent lack of overlapping triggers, make the development of a single therapeutic aimed at increasing both WAT and muscle mass incredibly difficult.…”

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confidence: 99%

The role of adipose tissue in cancer-associated cachexia

Vaitkus

Celi

2016

Exp Biol Med (Maywood)

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Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype – “beige” or “brite” adipose tissue – in a process referred to as “browning.” While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots – white, brown, and beige – to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing experiments, studies, and clinical trials.

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Mechanical regulation of mesenchymal stem cell differentiation

Cited by 193 publications

References 152 publications

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

Adipose, Bone Marrow and Synovial Joint-Derived Mesenchymal Stem Cells for Cartilage Repair

Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression

The role of adipose tissue in cancer-associated cachexia

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