Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle‐derived stem cells

Goldring, Mary B.

doi:10.1002/art.21756

Cited by 15 publications

(10 citation statements)

References 28 publications

(25 reference statements)

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“…MDSCs are of mesodermal origin. Numerous examples from the literature demonstrate the existence of a population of multipotential MDSCs that not only are able to differentiate into myogenic lineage and other mesodermal cell types including the adipogenic, osteogenic (Lee et al 2001), chondrogenic (Goldring 2006), endothelial, and hematopoietic (Williams et al 1999) lineages, but also possess the potential to break germ layer commitment and differentiate into ectodermal lineages including neuronlike cells under certain conditions (Kondo et al 2006). Reports of stem cell plasticity have generated both excitement and skepticism in the field of stem cell biology, as the concept of plasticity defies developmental biology principles of lineage restriction being imparted during morphogenesis.…”

Section: Differentiation Of Mdscsmentioning

confidence: 99%

Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy

Wang

Chen

et al. 2010

Cell Tissue Res

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Muscle tissue represents an abundant, accessible, and replenishable source of adult stem cells for cell-based tissue and genetic engineering. A population of cells isolated from muscle exhibits both multipotentiality and self-renewal capabilities. Satellite cells, referred to by many investigators as muscle stem cells, are myogenic precursors that are capable of regenerating muscle and that demonstrate self-renewal properties; however, they are considered to be committed to the myogenic lineage. Muscle-derived stem cells (MDSCs), which may represent a predecessor of the satellite cell, are considered to possess a higher regeneration capacity and to exhibit better cell survival and a broader range of multilineage capabilities. Remarkably, MDSCs are not only able to differentiate into mesodermal cell types including the myogenic, adipogenic, osteogenic, chondrogenic, endothelial, and hematopoietic lineages, but also possess the potential to break germ layer commitment and differentiate into ectodermal lineages including neuron-like cells under certain conditions. This article reviews the current preclinical studies and potential clinical applications of MDSC-mediated gene therapy and tissue-engineering and methods for MDSC isolation, differentiation, and molecular characterization.

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Section: Differentiation Of Mdscsmentioning

confidence: 99%

Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy

Wang

Chen

et al. 2010

Cell Tissue Res

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“…Findings that MSCs are available in adult tissues, including muscle, adipose tissue and synovium in addition to bone marrow, has prompted further investigations in animal models to determine the potential of these cells to participate in the repair of skeletal tissues (Goldring, 2006; Kuroda et al, 2006). Despite intensive investigation of cartilage repair strategies and the increased understanding of the cellular mechanisms involved, many issues remain to be resolved.…”

Section: Are Tissue Engineering and Gene Therapy Viable Approaches Inmentioning

confidence: 99%

Osteoarthritis

Goldring

2007

Journal Cellular Physiology

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1,110

954

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Osteoarthritis (OA) is characterized by degeneration of articular cartilage, limited intraarticular inflammation with synovitis, and changes in peri-articular and subchondral bone. Multiple factors are involved in the pathogenesis of OA, including mechanical influences, the effects of aging on cartilage matrix composition and structure, and genetic factors. Since the initial stages of OA involve increased cell proliferation and synthesis of matrix proteins, proteinases, growth factors, cytokines, and other inflammatory mediators by chondrocytes, research has focused on the chondrocyte as the cellular mediator of OA pathogenesis. The other cells and tissues of the joint, including the synovium and subchondral bone, also contribute to pathogenesis. The adult articular chondrocyte, which normally maintains the cartilage with a low turnover of matrix constituents, has limited capacity to regenerate the original cartilage matrix architecture. It may attempt to recapitulate phenotypes of early stages of cartilage development, but the precise zonal variations of the original cartilage cannot be replicated. Current pharmacological interventions that address chronic pain are insufficient, and no proven structure-modifying therapy is available. Cartilage tissue engineering with or without gene therapy is the subject of intense investigation. There are multiple animal models of OA, but there is no single model that faithfully replicates the human disease. This review will focus on questions currently under study that may lead to better understanding of mechanisms of OA pathogenesis and elucidation of effective strategies for therapy, with emphasis on mechanisms that affect the function of chondrocytes and interactions with surrounding tissues.

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“…Autologous cell transplantation circumvents the immunological and ethical concerns delaying cell therapy. Previous studies have discovered a population of multipotent skeletal muscle cells that differentiate into mesodermal lineages, including myogenic [7,8], adipogenic [9], osteogenic [10], chondrogenic [11], endothelial [12], and under certain conditions, they can break germ-layer commitment and differentiate into ectodermal lineages, including neural cells [3,13–17]. …”

Section: Introductionmentioning

confidence: 99%

Skeletal muscle neural progenitor cells exhibit properties of NG2-glia

Birbrair

Zhang

Wang

et al. 2013

Experimental Cell Research

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Reversing brain degeneration and trauma lesions will depend on cell therapy. Our previous work identified neural precursor cells derived from the skeletal muscle of Nestin-GFP transgenic mice, but their identity, origin, and potential survival in the brain are only vaguely understood. In this work, we show that Nestin-GFP+ progenitor cells share morphological and molecular markers with NG2-glia, including NG2, PDGFRα, O4, NGF receptor (p75), glutamate receptor-1(AMPA), and A2B5 expression. Although these cells exhibit NG2, they do not express other pericyte markers, such as α-SMA or connexin-43, and do not differentiate into the muscle lineage. Patch-clamp studies displayed outward potassium currents, probably carried through Kir6.1 channels. Given their potential therapeutic application, we compared their abundance in tissues and concluded that skeletal muscle is the richest source of predifferentiated neural precursor cells. We found that these cells migrate toward the neurogenic subventricular zone displaying their typical morphology and nestin-GFP expression two weeks after brain injection. For translational purposes, we sought to identify these neural progenitor cells in wild-type species by developing a DsRed expression vector under Nestin-Intron II control. This approach revealed them in nonhuman primates and aging rodents throughout the lifespan.

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Are bone morphogenetic proteins effective inducers of cartilage repair? Ex vivo transduction of muscle‐derived stem cells

Cited by 15 publications

References 28 publications

Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy

Muscle-derived stem cells: isolation, characterization, differentiation, and application in cell and gene therapy

Osteoarthritis

Skeletal muscle neural progenitor cells exhibit properties of NG2-glia

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