Control of mesenchymal cell fate via application of FGF-8b in vitro

Otsuka, Takayoshi; Mengsteab, Paulos Y.; Laurencin, Cato T.

doi:10.1016/j.scr.2021.102155

Cited by 12 publications

(15 citation statements)

References 91 publications

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“…Adult stem cells are tissue‐resident stem cells with properties of self‐renewal, maintenance of tissue homeostasis, and regeneration of damaged tissue. FGFs are common components of the adult stem cell niche and function to maintain quiescence and regulate self‐renewal and differentiation (Coutu & Galipeau, 2011; Keyes & Fuchs, 2018; Otsuka et al, 2021).…”

Section: Selected Topics In Genetics Development Regeneration and Dis...mentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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Section: Selected Topics In Genetics Development Regeneration and Dis...mentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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“…RT-qPCR and western blot were used to investigate the expression of tenocyte-related markers (Tnmd, Col I and Col III) and MMP-1 (degrade collagen fibrils) [ 23 , 37 ]. The expression of Tnmd decreased approximately 2.8 times after exposure to H 2 O 2 (vs. without exposure to H 2 O 2 , P < 0.001) and recovered 48 h after MSC treatment (vs. exposure to H 2 O 2 , P = 0.003) (Fig.…”

Section: Resultsmentioning

confidence: 99%

Mitochondrial transfer from bone mesenchymal stem cells protects against tendinopathy both in vitro and in vivo

Wei

Wang

et al. 2023

Stem Cell Res Ther

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Background Although mesenchymal stem cells (MSCs) have been effective in tendinopathy, the mechanisms by which MSCs promote tendon healing have not been fully elucidated. In this study, we tested the hypothesis that MSCs transfer mitochondria to injured tenocytes in vitro and in vivo to protect against Achilles tendinopathy (AT). Methods Bone marrow MSCs and H2O2-injured tenocytes were co-cultured, and mitochondrial transfer was visualized by MitoTracker dye staining. Mitochondrial function, including mitochondrial membrane potential, oxygen consumption rate, and adenosine triphosphate content, was quantified in sorted tenocytes. Tenocyte proliferation, apoptosis, oxidative stress, and inflammation were analyzed. Furthermore, a collagenase type I-induced rat AT model was used to detect mitochondrial transfer in tissues and evaluate Achilles tendon healing. Results MSCs successfully donated healthy mitochondria to in vitro and in vivo damaged tenocytes. Interestingly, mitochondrial transfer was almost completely blocked by co-treatment with cytochalasin B. Transfer of MSC-derived mitochondria decreased apoptosis, promoted proliferation, and restored mitochondrial function in H2O2-induced tenocytes. A decrease in reactive oxygen species and pro-inflammatory cytokine levels (interleukin-6 and -1β) was observed. In vivo, mitochondrial transfer from MSCs improved the expression of tendon-specific markers (scleraxis, tenascin C, and tenomodulin) and decreased the infiltration of inflammatory cells into the tendon. In addition, the fibers of the tendon tissue were neatly arranged and the structure of the tendon was remodeled. Inhibition of mitochondrial transfer by cytochalasin B abrogated the therapeutic efficacy of MSCs in tenocytes and tendon tissues. Conclusions MSCs rescued distressed tenocytes from apoptosis by transferring mitochondria. This provides evidence that mitochondrial transfer is one mechanism by which MSCs exert their therapeutic effects on damaged tenocytes.

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“…Tokunaga et al [ 93 ] reported that FGF-2 administration induced Scx expression in TSPCs and promoted tendon healing 4 and 8 weeks after in vivo cell transplantation, indicating that FGF-2 is a positive regulator of tenogenic differentiation and tendon repair. However, Otsuka et al [ 64 ] revealed that FGF-8b tended to reinforce chondrogenic differentiation while suppressing ASC tenogenic differentiation because the expression of tenogenic markers (Scx, Tnmd, and Tnc) and tendon extracellular matrix proteins (Col I and III) were downregulated. By contrast, the expression of the chondrogenic markers was upregulated after FGF-8b treatment.…”

Section: Strategies For Tenogenic Differentiationmentioning

confidence: 99%

Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair

Yuan

Long

et al. 2023

Stem Cells International

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Tendons are associated with a high injury risk because of their overuse and age-related tissue degeneration. Thus, tendon injuries pose great clinical and economic challenges to the society. Unfortunately, the natural healing capacity of tendons is far from perfect, and they respond poorly to conventional treatments when injured. Consequently, tendons require a long period of healing and recovery, and the initial strength and function of a repaired tendon cannot be completely restored as it is prone to a high rate of rerupture. Nowadays, the application of various stem cell sources, including mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs), for tendon repair has shown great potential, because these cells can differentiate into a tendon lineage and promote functional tendon repair. However, the mechanism underlying tenogenic differentiation remains unclear. Moreover, no widely adopted protocol has been established for effective and reproducible tenogenic differentiation because of the lack of definitive biomarkers for identifying the tendon differentiation cascades. This work is aimed at reviewing the literature over the past decade and providing an overview of background information on the clinical relevance of tendons and the urgent need to improve tendon repair; the advantages and disadvantages of different stem cell types used for boosting tendon repair; and the unique advantages of reported strategies for tenogenic differentiation, including growth factors, gene modification, biomaterials, and mechanical stimulation.

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Control of mesenchymal cell fate via application of FGF-8b in vitro

Cited by 12 publications

References 91 publications

New developments in the biology of fibroblast growth factors

New developments in the biology of fibroblast growth factors

Mitochondrial transfer from bone mesenchymal stem cells protects against tendinopathy both in vitro and in vivo

Stem Cell Applications and Tenogenic Differentiation Strategies for Tendon Repair

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