Exploiting Human CD34+ Stem Cell–conditioned Medium for Tissue Repair

Mintz, Paul J.; Huang, Kai‐Wen; Reebye, Vikash; Nteliopoulos, Georgios; Lai, Hong‐Shiee; Sætrom, Pål; Kasahara, Noriyuki; Jensen, S. L.; Pai, Madhava; Gordon, Myrtle Y.; Marley, Stephen B.; Behan, Rosemary; Spalding, Duncan; Haoudi, Abdelali; Emara, Mohamed M.; Nicholls, Joanna P.; Rossi, John J.; Habib, Nagy

doi:10.1038/mt.2013.194

Cited by 11 publications

(8 citation statements)

References 52 publications

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“…Since recent data have indicated that PARP1 interferes, in particular cases, with cell differentiation by sustaining transcription of pluripotency genes, we examined if some of these genes are differentially expressed in cultured HPSCs, which are documented to express known embryonic stem cell factors 15 , and in monocytes, which show a lower abundance of PARP1. As is shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

Downregulation of PARP1 transcription by promoter-associated E2F4-RBL2-HDAC1-BRM complex contributes to repression of pluripotency stem cell factors in human monocytes

Wiśnik

Płoszaj

Robaszkiewicz

2017

Sci Rep

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Differentiation of certain cell types is followed by a downregulation of PARP1 expression. We show that the reduction in the abundance of PARP1 in hematopoietic progenitor cells and monocytes is tightly controlled by the cell cycle. The differentiation-associated cell cycle exit induces E2F1 replacement with E2F4 at the PARP1 promoter and the assembly of an E2F4-RBL2-HDAC1-BRM(SWI/SNF) repressor complex which deacetylates nucleosomes and compacts chromatin. In G1 arrested cells, PARP1 transcription is reduced by the recruitment of E2F1-RB1-HDAC1-EZH2(PRC2)-BRM/BRG1(SWI/SNF), which additionally trimethylates H3K27 and causes an even higher increase in nucleosome density. The re-establishment of an active chromatin structure by treating post-mitotic monocytes with the HDAC inhibitor and G1 arrested cells with a combination of HDAC and EZH2 inhibitors restores PARP1 expression completely but does not affect the interaction between the components of the repressor complex with chromatin. This suggests that RB1 and RBL2, as well as PRC2, SWI/SNF and HDAC1, do not interfere with the transcription machinery. Interestingly, reinstatement of PARP1 expression by the silencing of RBL2 or by the inhibition of HDACs in monocytes and by transfection with the PARP1 expression vector in differentiated THP-1 cells substantially increased transcription of pluripotency stem cell factors such as POU5F1, SOX2 and NANOG.Although PARP1 is involved in the regulation of numerous intracellular processes such as DNA repair, gene transcription, signalling or metabolism, the differentiation of certain cell types is associated with downregulation of PARP1 transcription 1,2 . Decreased abundance of PARP1 also occurs in human monocytes derived from hematopoietic progenitor and stem cells (HSPCs), which belong to a group of multipotent cells capable of self-renewal and, upon stimulation, of giving rise to a wide range of blood cells. Lineage commitment in HPSC caused by cytokines or cell-cell signalling, involves the inhibition of cell cycle progression, repression of HPSC specific transcription factors and induction of lineage-specific expression of genes involved in cell fate. For example, PU.1 (also known as SPI-1) acts in monocytes/macrophages as a lineage-determining transcription factor 3 . Neither the mechanism nor the physiological significance of PARP1 repression in determining monocyte phenotype, function or differentiation has been documented. The low level of this enzyme has been shown to sensitise human monocytes to oxidative stress, while in myotubes it served as a protective mechanism against oxidative stress, helping with maintaining the cellular functions of skeletal muscles 4,5 . According to recent findings PARP1 repression favours commitment and differentiation of some cell types. In differentiating osteoclasts,

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Section: Resultsmentioning

confidence: 99%

Downregulation of PARP1 transcription by promoter-associated E2F4-RBL2-HDAC1-BRM complex contributes to repression of pluripotency stem cell factors in human monocytes

Wiśnik

Płoszaj

Robaszkiewicz

2017

Sci Rep

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“…Although no studies have confirmed the special role of CD34 and CD49f-specific stem cells in cartilage regeneration, the beneficial effects of CD34 + stem cells on cardiac repair and regeneration have been confirmed [ 56 ]. Studies have also found that the CM of CD34 + stem cells contains 32 soluble factors related to cell proliferation, survival, tissue repair, and wound healing, which can promote liver repair and regeneration in vivo [ 57 ]. MSCs with high expression of CD49f play an important role in the maintenance of hair follicle epithelial cells [ 58 ].…”

Section: Cartilage Regeneration Strategies Involving Stem Cellsmentioning

confidence: 99%

Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration

Jiang

Tian

et al. 2021

Stem Cells International

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Injury of articular cartilage can cause osteoarthritis and seriously affect the physical and mental health of patients. Unfortunately, current surgical treatment techniques that are commonly used in the clinic cannot regenerate articular cartilage. Regenerative medicine involving stem cells has entered a new stage and is considered the most promising way to regenerate articular cartilage. In terms of theories on the mechanism, it was thought that stem cell-mediated articular cartilage regeneration was achieved through the directional differentiation of stem cells into chondrocytes. However, recent evidence has shown that the stem cell secretome plays an important role in biological processes such as the immune response, inflammation regulation, and drug delivery. At the same time, the stem cell secretome can effectively mediate the process of tissue regeneration. This new theory has attributed the therapeutic effect of stem cells to their paracrine effects. The application of stem cells is not limited to exogenous stem cell transplantation. Endogenous stem cell homing and in situ regeneration strategies have received extensive attention. The application of stem cell derivatives, such as conditioned media, extracellular vesicles, and extracellular matrix, is an extension of stem cell paracrine theory. On the other hand, stem cell pretreatment strategies have also shown promising therapeutic effects. This article will systematically review the latest developments in these areas, summarize challenges in articular cartilage regeneration strategies involving stem cells, and describe prospects for future development.

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“…Stem cell-secreted factors have also been shown to improve recovery of liver from cirrhosis ( 81 ). In this case, Wistar rats poisoned with dimethylnitrosamine were treated with or without CM from CD34 + haematopoietic stem cells.…”

Section: Paracrine Effects Of Stem Cells In Tissue Regenerationmentioning

confidence: 99%

Paracrine effects of stem cells in wound healing and cancer progression

Dittmer¹,

Leyh²

2014

International Journal of Oncology

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Stem cells play an important role in tissue repair and cancer development. The capacity to self-renew and to differentiate to specialized cells allows tissue-specific stem cells to rebuild damaged tissue and cancer stem cells to initiate and promote cancer. Mesenchymal stem cells, attracted to wounds and cancer, facilitate wound healing and support cancer progression primarily by secreting bioactive factors. There is now growing evidence that, like mesenchymal stem cells, also tissue-specific and cancer stem cells manipulate their environment by paracrine actions. Soluble factors and microvesicles released by these stem cells have been shown to protect recipient cells from apoptosis and to stimulate neovascularization. These paracrine mechanisms may allow stem cells to orchestrate wound healing and cancer progression. Hence, understanding these stem cell-driven paracrine effects may help to improve tissue regeneration and cancer treatment.

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Exploiting Human CD34+ Stem Cell–conditioned Medium for Tissue Repair

Cited by 11 publications

References 52 publications

Downregulation of PARP1 transcription by promoter-associated E2F4-RBL2-HDAC1-BRM complex contributes to repression of pluripotency stem cell factors in human monocytes

Downregulation of PARP1 transcription by promoter-associated E2F4-RBL2-HDAC1-BRM complex contributes to repression of pluripotency stem cell factors in human monocytes

Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration

Paracrine effects of stem cells in wound healing and cancer progression

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