Reproductive Stem Cell Differentiation: Extracellular Matrix, Tissue Microenvironment, and Growth Factors Direct the Mesenchymal Stem Cell Lineage Commitment

Vidane, Atanásio Serafim; Zomer, Helena Debiazi; Oliveira, Bruna Marcele Martins de; Guimarães, Carina de Fátima; Fernandes, Claudia Barbosa; Perecin, Felipe; Silva, Luciano Andrade; Miglino, María Angélica; Meirelles, Flávio Vieira; Ambrósio, Carlos Eduardo

doi:10.1177/1933719113477484

Cited by 34 publications

(25 citation statements)

References 85 publications

(212 reference statements)

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“…Although ASC isolation from the adipose tissue is more efficient than DSCs from dermis, the latter show a higher proliferation and amplification potential and greater in vitro wound closure capacity. This could be related to their natural niche, because the influence of the tissue microenvironment (growth factors and extracellular matrix) on the behaviour of MSC was previously described (Vidane et al, 2013). For instance, olfactory mucosa-derived MSCs have greater neurogenic potential than bone marrow MSCs (Lindsay et al, 2013).…”

Section: Discussionmentioning

confidence: 91%

In vitro comparative study of human mesenchymal stromal cells from dermis and adipose tissue for application in skin wound healing

Zomer

Varela

Delben

et al. 2019

J Tissue Eng Regen Med

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Novel strategies combining cell therapy, tissue engineering, and regenerative medicine have been developed to treat major skin wounds. Although mesenchymal stromal cells (MSCs) from different tissues have similar stem cell features, such as self‐renewing mesodermal differentiation potential and expression of immunophenotypic markers, they also have distinct characteristics. Therefore, we aimed to characterize the application of MSCs derived from the dermis and adipose tissue (DSCs and ASCs, respectively) in cutaneous wound healing by in vitro approaches. Human DSC and ASC were obtained and evaluated for their isolation efficiency, stemness, proliferative profile, and genetic stability over time in culture. The ability of wound closure was first assessed by direct cell scratch assay. The paracrine effects of DSC‐ and ASC‐conditioned medium in dermal fibroblasts and keratinocytes and in the induction of tubule formation were also investigated. Although the ASC isolation procedures resulted in 100 times more cells than DSC, the latter had a higher proliferation rate in culture. Both presented low frequency of nuclear alterations over time in culture and showed similar characteristics of stem cells, such as expression of immunophenotypic markers and differentiation potential. DSCs showed increased healing capacity, and their conditioned media had greater paracrine effect in closing the wound of dermal fibroblasts and keratinocytes and in inducing angiogenesis. In conclusion, the therapeutic potential of MSCs is influenced by the obtainment source. Both ASCs and DSCs are applicable for skin wound healing; however, DSCs have an improved potential and should be considered for future applications in cell therapy.

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Section: Discussionmentioning

confidence: 91%

In vitro comparative study of human mesenchymal stromal cells from dermis and adipose tissue for application in skin wound healing

Zomer

Varela

Delben

et al. 2019

J Tissue Eng Regen Med

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“…BM-MSCs differentiate into OBs, chondrocytes and adipocytes (5) and are therefore considered the main source of bone regeneration and remodeling during homeostasis (6–9). Much of this process depends on the ability of MSCs to proliferate and differentiate under the influence of biologically active molecules (i.e., growth factors) (10–13). The role of growth factors in bone repair is widely recognized, particularly for platelet-derived growth factor (PDGF), insulin-like growth factor-I (IGF-I), vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β), all of which are inducers, particularly in osteoprogenitor cells (14).…”

Section: Introductionmentioning

confidence: 99%

PDGF-induced PI3K-mediated signaling enhances the TGF-β-induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner

Yokota

Chosa

Sawada

et al. 2013

International Journal of Molecular Medicine

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Transforming growth factor-β (TGF-β) is a critical regulator of osteogenic differentiation and the platelet-derived growth factor (PDGF) is a chemoattractant or mitogen of osteogenic mesenchymal cells. However, the combined effects of these regulators on the osteogenic differentiation of mesenchymal cells remains unknown. In this study, we investigated the effects of TGF-β and/or PDGF on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). The TGF-β-induced osteogenic differentiation of UE7T-13 cells, a bone marrow-derived hMSC line, was markedly enhanced by PDGF, although PDGF alone did not induce differentiation. TGF-β induced extracellular signal-regulated kinase (ERK) phosphorylation and PDGF induced Akt phosphorylation. In addition, the mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) inhibitor, U0126, suppressed the osteogenic differentiation induced by TGF-β alone. Moreover, U0126 completely suppressed the osteogenic differentiation synergistically induced by TGF-β and PDGF, whereas the phosphoinositide-3-kinase (PI3K) inhibitor, LY294002, only partially suppressed this effect. These results suggest that the enhancement of TGF-β-induced osteogenic differentiation by PDGF-induced PI3K/Akt-mediated signaling depends on TGF-β-induced MEK activity. Thus, PDGF positively modulates the TGF-β-induced osteogenic differentiation of hMSCs through synergistic crosstalk between MEK- and PI3K/Akt-mediated signaling.

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“…In-vivo, the ECM produced by fibroblasts, osteoblasts and chondroblasts [39] provides pivotal biochemical and physical cues that guide stem cell development and lineage commitment [40–42]. We therefore explored osteo-inductive and osteo-conductive abilities of a new generation of fibrous scaffolds impregnated with decellularized matrix produced by fibroblasts or chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

et al. 2016

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A predictive framework for the evolution of stem cell biology in 3-D is currently lacking. In this study we propose deep image informatics of the nuclear biology of stem cells to elucidate how 3-D biomaterials steer stem cell lineage phenotypes. The approach is based on high content imaging informatics to capture minute variations in the 3-D spatial organization of splicing factor SC-35 in the nucleoplasm as a marker to classify emergent cell phenotypes of human mesenchymal stem cells (hMSCs). The cells were cultured in varied 3-D culture systems including hydrogels, electrospun mats and salt leached scaffolds. The approach encompasses high resolution 3-D imaging of SC-35 domains and high content image analysis (HCIA) to compute quantitative 3-D nuclear metrics for SC-35 organization in single cells in concert with machine learning approaches to construct a predictive cell-state classification model. Our findings indicate that hMSCs cultured in collagen hydrogels and induced to differentiate into osteogenic or adipogenic lineages could be classified into the three lineages (stem, adipogenic, osteogenic) with ≥ 80% precision and sensitivity, within 72 hours. Using this framework, the augmentation of osteogenesis by scaffold design exerted by porogen leached scaffolds was also profiled within 72 hours with ~80% high sensitivity. Furthermore, by employing 3-D SC-35 organizational metrics, differential osteogenesis induced by novel electrospun fibrous polymer mats incorporating decellularized matrix could also be elucidated and predictably modeled at just 3 days with high precision. We demonstrate that 3-D SC-35 organizational metrics can be applied to model the stem cell state in 3-D scaffolds. We propose that this methodology can robustly discern minute changes in stem cell states within complex 3-D architectures and map single cell biological readouts that are critical to assessing population level cell heterogeneity.

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Reproductive Stem Cell Differentiation: Extracellular Matrix, Tissue Microenvironment, and Growth Factors Direct the Mesenchymal Stem Cell Lineage Commitment

Cited by 34 publications

References 85 publications

In vitro comparative study of human mesenchymal stromal cells from dermis and adipose tissue for application in skin wound healing

In vitro comparative study of human mesenchymal stromal cells from dermis and adipose tissue for application in skin wound healing

PDGF-induced PI3K-mediated signaling enhances the TGF-β-induced osteogenic differentiation of human mesenchymal stem cells in a TGF-β-activated MEK-dependent manner

Profiling stem cell states in three-dimensional biomaterial niches using high content image informatics

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