Human adipose tissue‐derived tenomodulin positive subpopulation of stem cells: A promising source of tendon progenitor cells

Self Cite

Strategies aiming at controlling and modulating inflammatory cues may offer therapeutic solutions for improving tendon regeneration. This study aims to investigate the modulatory effect of pulsed electromagnetic field (PEMF) on the inflammatory profile of human tendon‐derived cells (hTDCs) after supplementation with interleukin‐1β (IL‐1β). IL‐1β was used to artificially induce inflammatory cues associated with injured tendon environments. The PEMF effect was investigated varying the frequency (5 or 17 Hz), intensity (1.5, 4, or 5 mT), and duty‐cycle (10% or 50%) parameters to which IL‐1β‐treated hTDCs were exposed to. A PEMF actuation with 4 mT, 5 Hz and a 50% duty cycle decreased the production of IL‐6 and tumor necrosis factor‐α (TNF‐α), as well as the expression of TNFα, IL‐6, IL‐8, COX‐2, MMP‐1, MMP‐2, and MMP‐3, while IL‐4, IL‐10, and TIMP‐1 expression increased. These results suggest that PEMF stimulation can modulate hTDCs response in an inflammatory environment holding therapeutic potential for tendon regenerative strategies. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:160–172, 2020

mentioning

confidence: 99%

Pulsed Electromagnetic Field Modulates Tendon Cells Response in IL‐1β‐Conditioned Environment

Vinhas

Rodrigues

Gonçalves

et al. 2019

Self Cite

“…MSCs are readily available from autologous sources, including bone marrow and adipose tissue. Adipose‐derived MSCs (ASCs) are particularly attractive because they are easier to obtain and more abundant than bone marrow‐derived MSCs . These cells have the capacity to differentiate into multiple lineages, including tendon fibroblasts, osteoblasts, chondrocytes, and adipocytes .…”

mentioning

confidence: 99%

“…Adipose-derived MSCs (ASCs) are particularly attractive because they are easier to obtain and more abundant than bone marrow-derived MSCs. 11 These cells have the capacity to differentiate into multiple lineages, including tendon fibroblasts, osteoblasts, chondrocytes, and adipocytes. 12 A number of strategies have been used to promote tenogenesis of MSCs, including growth factors and mechanical stimulation, but the molecular cues driving such process are unclear.…”

mentioning

confidence: 99%

CTGF induces tenogenic differentiation and proliferation of adipose‐derived stromal cells

Pongkitwitoon

et al. 2019

Intrasynovial tendons are paucicellular and hypovascular, resulting in a poor response to injury. Surgical repair of ruptured or lacerated tendons often lead to complications such as adhesions, repair site gapping, and repair site rupture. Adipose‐derived stem cells (ASCs) have shown promise for enhancing tendon repair, as they have the capacity to differentiate into tendon fibroblasts and augment the healing response. Furthermore, connective tissue growth factor (CTGF) has been shown to promote tendon regeneration via the stimulation of endogenous tendon stem cells. Here, we evaluated the potential of CTGF to promote tenogenic differentiation of ASCs in vitro. Gene and protein expression, cell proliferation, and FAK and ERK1/2 signaling were assessed. CTGF increased tenogenic genes in mouse ASCs in a dose‐ and time‐dependent manner. Western blot and immunostaining analyses demonstrated increases in tenogenic protein expression in CTGF‐treated ASCs at all timepoints studied. CTGF increased ASC proliferation in a dose‐dependent manner. CTGF induced phosphorylation of ERK1/2 within 5 min and FAK within 15 min; both signals persisted for 120 min. Blocking FAK and ERK1/2 pathways by selective inhibitors SCH772984 and PF573228, respectively, attenuated the CTGF‐induced tenogenic differentiation and proliferation of ASCs. These results suggest that CTGF induces tenogenic differentiation of ASCs via the FAK and ERK1/2 pathway. Statement of clinical significance: Although prior research has led to advances in tendon operative techniques and rehabilitation methods, clinical outcomes after tendon repair remain variable, with high rates of repair site gapping or rupture. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

“…Multipotent stromal cells have the potential to influence tendon healing by several mechanisms, including differentiation into tendon fibroblasts, production of soluble factors that influence healing by inducing cell proliferation, differentiation, and migration, and immunomodulatory effects . The production of soluble factors that act as paracrine mediators is referred to as “trophic” activity and can occur directly through the production and release of bioactive factors or indirectly by recruiting endogenous cells capable of doing the same . In tendon healing, growth factors and cytokines act as chemoattractants (stromal cell‐derived factor‐1α [SDF‐1α] and platelet‐derived growth factor‐BB [PDGF‐BB]) and to modulate cell proliferation and differentiation (transforming growth factor‐β1 [TGF‐β1] and ‐β3, fibroblast growth factor [FGF‐2], and insulin‐like growth factor‐1 [IGF‐1]) …”

mentioning

confidence: 99%

“…8,14,19 The production of soluble factors that act as paracrine mediators is referred to as "trophic" activity and can occur directly through the production and release of bioactive factors or indirectly by recruiting endogenous cells capable of doing the same. 14,[20][21][22][23][24][25][26] In tendon healing, growth factors and cytokines act as chemoattractants (stromal cell-derived factor-1α [SDF-1α] and platelet-derived growth factor-BB [PDGF-BB]) 22,[27][28][29][30] and to modulate cell proliferation and differentiation (transforming growth factor-β1 [TGF-β1] and -β3, fibroblast growth factor [FGF-2], and insulinlike growth factor-1 [IGF-1]). 22,[30][31][32][33] The trophic capabilities of adult stem cells are increasingly the focus of many investigations, yet direct evidence that SVF and ASC can improve tendon healing by the production of bioactive soluble factors remains limited.…”

mentioning

confidence: 99%

Adipose‐Derived Stromal Vascular Fraction and Cultured Stromal Cells as Trophic Mediators for Tendon Healing

Polly

Nichols

Donnini

et al. 2019

Adipose‐derived stromal vascular fraction (SVF) is a heterogeneous population of cells that yields a homogeneous population of plastic‐adherent adipose tissue‐derived stromal cells (ASC) when culture‐expanded. SVF and ASC have been used clinically to improve tendon healing, yet their mechanism of action is not fully elucidated. The objective of this study was to investigate the potential for ASC to act as trophic mediators for tendon healing. Flexor digitorum superficialis tendons and adipose tissue were harvested from adult horses to obtain SVF, ASC, and tenocytes. Growth factor gene expression was quantified in SVF and ASC in serial passages and growth factors were quantified in ASC‐conditioned medium (CM). Microchemotaxis assays were performed using ASC‐CM. Tenocytes were grown in co‐culture with autologous ASC or allogeneic SVF. Gene expression for insulin‐like growth factor 1 (IGF‐1), stromal cell‐derived factor‐1α (SDF‐1α), transforming growth factor‐β1 (TGF‐β1) and TGF‐β3 was significantly higher in SVF compared to ASC. Concentrations were significantly increased in ASC‐CM compared to controls for IGF‐1 (4‐fold) and SDF‐1α (6‐fold). Medium conditioned by ASC induced significant cell migration in a dose‐dependent manner. Gene expression for collagen types I and III, decorin, and cartilage oligomeric matrix protein was modestly, but significantly increased following co‐culture of tenocytes with autologous ASC. Our findings support the ability of SVF and ASC to act as trophic mediators in tendon healing, particularly through chemotaxis, which stands to critically impact the intrinsic healing response. In vivo studies to further delineate the potential for SVF and/or ASC to improve tendon healing are warranted. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1429–1439, 2019.