Identification of a Candidate Proteomic Signature to Discriminate Multipotent and Non-Multipotent Stromal Cells

Rosu‐Myles, Michael; She, Yi‐Min; Fair, Joel; Muradia, Gauri; Mehic, Jelica; Menéndez, Pablo; Prasad, Shiv S.; Cyr, Terry D.

doi:10.1371/journal.pone.0038954

Cited by 11 publications

(6 citation statements)

References 59 publications

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“…Our findings showing that genes associated with MSC differentiation and osteogenic development were significantly downregulated in the KO Rb-niche, together with a lack of calcium deposition in vitro, are strongly supportive. Our data also show that genes enriched in multipotent stromal cells (e.g., Nrp1, Yap1, CD248) compared to those less potent (Rosu-Myles et al, 2012), were significantly downregulated in the KO Rb-niche. However, the perivascular-MSC-hematopoietic support axis in vivo in which PDGFRb is a central network controller has not been described so far in the mouse.…”

Section: Pericyte Precursors and The Osteogenic And Hematopoietic Nichesupporting

confidence: 67%

PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

Bandeira¹,

Kilpatrick²,

Marques³

et al. 2022

Cell Reports

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Section: Pericyte Precursors and The Osteogenic And Hematopoietic Nichesupporting

confidence: 67%

PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

Bandeira¹,

Kilpatrick²,

Marques³

et al. 2022

Cell Reports

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“…However, the reduction of CD105 cannot reach the level induced by greater than 2.5 μM GSI-I, the doses of inducing apoptosis, thus suggesting the surface markers served as a part of minimal criteria for defining MSCs may be subjective to Notch, proteasome and even cell death-associated regulations. CD105 is also known as endoglin and involved in multiple functions of MSCs, such as differentiation, angiogenesis, and regenerative potential [ 45 – 47 ]. The more significant change observed in CD105 than in CD73 and CD90 may suggest that CD105 is more sensitive than other positive markers to the viability-associated events, thus suggesting that CD105 may be used as a surrogate marker to indicate the occurrence of cell death.…”

Section: Discussionmentioning

confidence: 99%

The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells

Liu

Zhang

et al. 2015

PLoS ONE

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Mesenchymal stem cells (MSCs) are a group of multipotent cells with key properties of multi-lineage differentiation, expressing a set of relatively specific surface markers and unique immunomodulatory functions. IDO1, a catabolic enzyme of tryptophan, represents a critical molecule mediating immunomodulatory functions of MSCs. However, the signaling pathways involved in regulating these key properties still remain elusive. To investigate the involvement of Notch signaling as well as other potential signaling pathway(s) in regulating these critical properties of MSCs, we treated human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) with γ-secreatase inhibitor I (GSI-I), which inhibits both Notch signaling and ubiquitin-proteasome activities. It was shown that the GSI-I treatment resulted in apoptosis, reduced expression of surface markers CD73, CD90 and CD105, reduced osteogenic differentiation, and reduction of the hUC-MSCs-mediated suppression of Th1 lymphocyte proliferation and the IFN-γ-induced IDO1 expression. Through distinguishing the effects of GSI-I between Notch inhibition and proteasome inhibition, it was further observed that, whereas both Notch inhibition and proteasome inhibition were attributable to the reduced CD105 expression and osteogenic differentiation, but not to the induced apoptosis. However, Notch inhibition, but not proteasome inhibition, only contributed to the significant effect of GSI-I on Th1 proliferation probably through reducing IDO1 promoter activity. In conclusion, the Notch signaling may represent a very important cell signaling capable of regulating multiple critical properties, especially the immunomodulatory functions of MSCs.

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“…We further performed hBM-MSC characterization using population doublings, hBM-MSC surface markers, and differentiation potential (Supplementary Table 1). hBM-MSCs were differentiated following a previously described protocol [31]. For RB cells, StemXVivo Chondrogenic Base Media (cat.#CCM005, R&D Systems; Minneapolis, MN, USA) were used for the basal media for chondrocytes.…”

Section: Methodsmentioning

confidence: 99%

Efficient Nonviral Transfection of Human Bone Marrow Mesenchymal Stromal Cells Shown Using Placental Growth Factor Overexpression

Cheung

Hovey

Gobin

et al. 2018

Stem Cells International

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Background Human mesenchymal stromal/stem cells (hMSCs) hold great therapeutic potential due to their immunomodulatory and tissue regenerative properties. Enhancement of biological features of hMSCs by transfection has become a focus of investigation for cell- and gene-based therapies. However, many of the current transient transfection methods result in either low transfection efficiency or high cytotoxicity. Methods In order to find a transfection method that would address the current issues of low transfection efficiency and high cytotoxicity, 6 commercially available cationic lipid and polymer reagents were tested on human bone marrow-derived MSCs (hBM-MSCs) using GFP as a reporter gene. One transfection method using TransIT-2020 was selected and tested with an emphasis on cell quality (viability, identity, and yield), as well as efficacy with a human placental growth factor (PlGF) plasmid. Results TransIT-2020 yielded the highest fluorescence signal per cell out of the methods that did not decrease cell recovery. Transfecting GFP to 5 hBM-MSC donors using TransIT-2020 yielded 24–36% GFP-expressing cells with a viability of 85–96%. hBM-MSC identity was unaffected as CD90, CD105, and CD73 markers were retained (>95%+) after transfection. When this method was applied to PlGF expression, there was up to a 220-fold increase in secretion. Both growth and secretion of PlGF in overexpressing hBM-MSC were sustained over 7 days, confirming the sustainability and applicability of the TransIT-2020 transfection system. Discussion We report a simple and efficient method for transient transfection that has not been reported for hBM-MSCs, encompassing high levels of plasmid expression without significant changes to fundamental hBM-MSC characteristics.

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Identification of a Candidate Proteomic Signature to Discriminate Multipotent and Non-Multipotent Stromal Cells

Cited by 11 publications

References 59 publications

PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

PDGFRβ+ cells play a dual role as hematopoietic precursors and niche cells during mouse ontogeny

The Notch Signaling Regulates CD105 Expression, Osteogenic Differentiation and Immunomodulation of Human Umbilical Cord Mesenchymal Stem Cells

Efficient Nonviral Transfection of Human Bone Marrow Mesenchymal Stromal Cells Shown Using Placental Growth Factor Overexpression

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