Insulin-Like Growth Factor Binding Protein-6 Alters Skeletal Muscle Differentiation of Human Mesenchymal Stem Cells

Aboalola, Doaa; Han, V. K. M.

doi:10.1155/2017/2348485

Cited by 7 publications

(24 citation statements)

References 52 publications

(59 reference statements)

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“…After surgery, chorionic villi were dissected, washed, minced with surgical scissors and forceps, and then subjected to enzymatic digestion with collagenase IV (369 IU/mg), hyaluronidase (999 IU/mg) (Sigma-Aldrich, Oakville, ON), and DNase I (2000 IU/mg) (Hoffmann-La Roche, Mississauga, ON) for 10 minutes at room temperature, followed by 0.05% trypsin (Gibco/Invitrogen, Mississauga, ON) for 5 minutes at room temperature. The sample was then washed for 10 minutes with 10% FBS in DMEM/F12 medium, and the resulting single cell suspension was separated by density centrifugation over a Percoll (Sigma-Aldrich, Oakville, ON) discontinuous gradient using a modified protocol by Worton et al [ 25 , 26 ]. PMSCs isolated were validated for the expression of stem cell markers (CD73, CD105, and CD-117/c-Kit) and differentiation ability [ 26 ].…”

Section: Methodsmentioning

confidence: 99%

Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells

Aboalola

Han

2017

Stem Cells International

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Insulin-like growth factors (IGFs) are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle. We have previously reported that insulin-like growth factor binding protein-6 (IGFBP-6), which has high affinity for IGF-2, alters the differentiation process of placental mesenchymal stem cells (PMSCs) into skeletal muscle. In this study, we determined the roles of IGF-1 and IGF-2 and their interactions with IGFBP-6. We showed that IGF-1 increased IGFBP-6 levels within 24 hours but decreased after 3 days, while IGF-2 maintained higher levels of IGFBP-6 throughout myogenesis. IGF-1 increased IGFBP-6 in the early phase as a requirement for muscle commitment. In contrast, IGF-2 enhanced muscle differentiation as shown by the expression of muscle differentiation markers MyoD, MyoG, and MHC. IGF-1 and IGF-2 had different effects on muscle differentiation with IGF-1 promoting early commitment to muscle and IGF-2 promoting complete muscle differentiation. We also showed that PMSCs acquired increasing capacity to synthesize IGF-2 during muscle differentiation, and the capacity increased as the differentiation progressed suggesting an autocrine and/or paracrine effect. Additionally, we demonstrated that IGFBP-6 could enhance the muscle differentiation process in the absence of IGF-2.

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Section: Methodsmentioning

confidence: 99%

Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells

Aboalola

Han

2017

Stem Cells International

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“…Journal of Molecular Endocrinology of IGFBP6 enhanced their differentiation (Aboalola & Han 2017). Silencing IGFBP6 decreased differentiation suggesting an important role in muscle cell commitment.…”

Section: Igfbp6mentioning

confidence: 96%

40 YEARS OF IGF1: Role of IGF-binding proteins in regulating IGF responses to changes in metabolism

Clemmons

2018

Journal of Molecular Endocrinology

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The IGF-binding protein family contains six members that share significant structural homology. Their principal function is to regulate the actions of IGF1 and IGF2. These proteins are present in plasma and extracellular fluids and regulate access of both IGF1 and II to the type I IGF receptor. Additionally, they have functions that are independent of their ability to bind IGFs. Each protein is regulated independently of IGF1 and IGF2, and this provides an important mechanism by which other hormones and physiologic variables can regulate IGF actions indirectly. Several members of the family are sensitive to changes in intermediary metabolism. Specifically the presence of obesity/insulin resistance can significantly alter the expression of these proteins. Similarly changes in nutrition or catabolism can alter their synthesis and degradation. Multiple hormones such as glucocorticoids, androgens, estrogen and insulin regulate IGFBP synthesis and bioavailability. In addition to their ability to regulate IGF access to receptors these proteins can bind to distinct cell surface proteins or proteins in extracellular matrix and several cellular functions are influenced by these interactions. IGFBPs can be transported intracellularly and interact with nuclear proteins to alter cellular physiology. In pathophysiologic states, there is significant dysregulation between the changes in IGFBP synthesis and bioavailability and changes in IGF1 and IGF2. These discordant changes can lead to marked alterations in IGF action. Although binding protein physiology and pathophysiology are complex, experimental results have provided an important avenue for understanding how IGF actions are regulated in a variety of physiologic and pathophysiologic conditions.

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“…Other studies support the importance of Notch signaling during the differentiation of MSCs into cardiomyocytes [81][82][83]. IGF signaling has also been shown to regulate the myogenesis of placenta MSCs as silencing of IGF binding proteins blocked lineage commitment in placenta-derived MSCs [31].…”

Section: Discussionmentioning

confidence: 90%

“…It is noteworthy to point out that others have shown that some human bmMSC cultures expanded in 10% FBS expressed MyoD, MyoG, and MHC as determined by PCR and/or immunofluorescence [79,80]. Moreover, human placenta- [31], umbilical cord- [32], and adiposederived MSC studies [33,34] have shown that MSCs from these tissues are capable of undergoing skeletal muscle lineage commitment using FBS expansion followed by treatment with HS. Even after up to 28 days of culture in P/PL, we did not observe the expression of myogenic markers in human bmMSCs (data not shown).…”

Section: Discussionmentioning

confidence: 99%

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Lack of a skeletal muscle phenotype in adult human bone marrow stromal cells following xenogeneic-free expansion

et al. 2020

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Background: Many studies have elegantly shown that murine and rat bone marrow-derived mesenchymal stromal cells (bmMSCs) contribute to muscle regeneration and improve muscle function. Yet, the ability of transplanted human bmMSCs to manifest myogenic potential shows conflicting results. While human adipose-and umbilical cord-derived MSCs can be differentiated into a skeletal muscle phenotype using horse serum (HS), bmMSCs have only been shown to differentiate towards the skeletal muscle lineage using a complex mixture of cytokines followed by transfection with notch intracellular domain. Methods: Since xenogeneic-free growth supplements are increasingly being used in the expansion of bmMSCs in clinical trials, we investigated the effects of human plasma and platelet lysate (P/PL) on the expression of neuromuscular markers and whether P/PL-expanded human bmMSCs could be differentiated towards a skeletal myogenic phenotype. Neuromuscular markers were measured using the highly sensitive droplet digital polymerase chain reaction for measuring the expression of Myf5, MyoD, MyoG, ACTA1, Desmin, GAP-43, and Coronin 1b transcripts, by performing immunofluorescence for the expression of Desmin, GAP-43, and MEF2, and flow cytometry for the expression of CD56/neural cell adhesion molecule (NCAM). Results: Despite that bmMSCs expressed the myogenic regulatory factor (MRF) MEF2 after expansion in P/PL, bmMSCs cultured under such conditions did not express other essential MRFs including Myf5, MyoD, MyoG, or ACTA1 needed for myogenesis. Moreover, HS did not induce myogenesis of bmMSCs and hence did not induce the expression of any of these myogenic markers. P/PL, however, did lead to a significant increase in neurogenic GAP-43, as well as Desmin expression, and resulted in a high baseline expression of the neurogenic gene Coronin 1b which was sustained under further P/PL or HS culture conditions. Fetal bovine serum resulted in equally high levels of GAP-43 and Coronin 1b. Moreover, the proportion of CD56/NCAM-positive bmMSCs cultured in P/PL was 5.9 ± 2.1. Conclusions: These data suggest that P/PL may prime a small portion of bmMSCs towards an early neural precursor cell type. Collectively, this shows that P/PL partially primes the cells towards a neurogenic phenotype, but does not prime adult human bmMSCs towards the skeletal muscle lineage.

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Insulin-Like Growth Factor Binding Protein-6 Alters Skeletal Muscle Differentiation of Human Mesenchymal Stem Cells

Cited by 7 publications

References 52 publications

Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells

Different Effects of Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 on Myogenic Differentiation of Human Mesenchymal Stem Cells

40 YEARS OF IGF1: Role of IGF-binding proteins in regulating IGF responses to changes in metabolism

Lack of a skeletal muscle phenotype in adult human bone marrow stromal cells following xenogeneic-free expansion

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