Mesenchymal stem cells in health and disease

Uccelli, Antonio; Moretta, Alessandro; Pistoia, Vito

doi:10.1038/nri2395

Cited by 3,179 publications

(2,798 citation statements)

References 118 publications

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“…The systemic injection of MSCs and NPCs is remarkably immune regulatory in vivo (Martino and Pluchino, 2006;Spaggiari and Moretta, 2012;Uccelli et al, 2008).…”

Section: Modulation Of Immune Responsesmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

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Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

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“…The systemic injection of MSCs and NPCs is remarkably immune regulatory in vivo (Martino and Pluchino, 2006;Spaggiari and Moretta, 2012;Uccelli et al, 2008).…”

Section: Modulation Of Immune Responsesmentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

111

109

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“…However, it has recently been shown, that embryonic MSC derived from the neuroepithelium and neural crest (68). It has been suggested that in post-natal life the relative importance of MSC derived from other developmental lineages decreases due to the increasing importance of mesodermal MSC (69). Because of the differentiation capacity, it has been proposed that MSC could be used for the regeneration of different tissues.…”

Section: Ig Gene Rearrangementmentioning

confidence: 99%

Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia

et al. 2010

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“…1 Adipogenesis and osteogenesis have a reciprocal relationship in common mesenchymal precursor cells. 2 Disruption of the balance in these processes during MSC differentiation leads to disorders, such as obesity, skeletal fragility, and osteoporosis.…”

mentioning

confidence: 99%

“…2 Disruption of the balance in these processes during MSC differentiation leads to disorders, such as obesity, skeletal fragility, and osteoporosis. 1 MSC differentiation is regulated by specific transcription factors. MSCs differentiate into adipocytes when they express peroxisome proliferator-activated receptor g 2 (PPARg 2 ), which enhances expression of adipogenic genes.…”

mentioning

confidence: 99%

A novel PPARγ2 modulator sLZIP controls the balance between adipogenesis and osteogenesis during mesenchymal stem cell differentiation

Kim

2014

Cell Death Differ

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Mesenchymal stem cells (MSCs), also known as multipotent stromal cells, are used in clinical trials. However, the use of MSCs for medical treatment of patients poses a potential problem due to the possibility of transdifferentiation into unwanted tissues. Disruption of the balance during MSC differentiation leads to obesity, skeletal fragility, and osteoporosis. Differentiation of MSCs into either adipocytes or osteoblasts is transcriptionally regulated by the two key transcription factors PPARc 2 and Runx2. PPARc 2 is highly expressed during adipocyte differentiation and regulates expression of genes involved in adipogenesis. Runx2 induces osteogenic gene expression and, thereby, increases osteoblast differentiation. Although transcriptional modulation of PPARc 2 has been investigated in adipogenesis, the underlying molecular mechanisms to control the balance between adipogenesis and osteogenesis in MSCs remain unclear. In this study, the role of sLZIP in regulation of PPARc 2 transcriptional activation was investigated along with sLZIP's involvement in differentiation of MSCs into adipocytes and osteoblasts. sLZIP interacts with PPARc 2 and functions as a corepressor of PPARc 2 . sLZIP enhances formation of the PPARc 2 corepressor complex through specific interaction with HDAC3, resulting in suppression of PPARc 2 transcriptional activity. We found that sLZIP prevents expression of PPARc 2 target genes and adipocyte differentiation both in vitro and in vivo. sLZIP also upregulates Runx2 transcriptional activity via inhibition of PPARc 2 activity, and promotes osteoblast differentiation. sLZIP transgenic mice exhibited enhanced bone mass and density, compared with wild-type mice. These results indicate that sLZIP has a critical role in the regulation of osteogenesis and bone development. However, sLZIP does not affect chondrogenesis and osteoclastogenesis. We propose that sLZIP is a novel PPARc 2 modulator for control of the balance between adipogenesis and osteogenesis during MSC differentiation, and that sLZIP can be used as a therapeutic target molecule for treatment of obesity, osteodystrophy, and osteoporosis. Mesenchymal stem cells (MSCs) are bone marrow-derived multipotential stromal cells that can differentiate into several distinct cell types, including fat, bone, cartilage, and muscle. 1 Adipogenesis and osteogenesis have a reciprocal relationship in common mesenchymal precursor cells. 2 Disruption of the balance in these processes during MSC differentiation leads to disorders, such as obesity, skeletal fragility, and osteoporosis. 1 MSC differentiation is regulated by specific transcription factors. MSCs differentiate into adipocytes when they express peroxisome proliferator-activated receptor g 2 (PPARg 2 ), which enhances expression of adipogenic genes. 2 Runt-related transcription factor 2 (Runx2) enhances expression of osteogenic genes during osteoblast differentiation; however, PPARg 2 suppresses osteogenesis via inhibition of Runx2 transcriptional activity. 3 Therefore, characterization of the ...

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Mesenchymal stem cells in health and disease

Cited by 3,179 publications

References 118 publications

How stem cells speak with host immune cells in inflammatory brain diseases

How stem cells speak with host immune cells in inflammatory brain diseases

Leukemia-associated genetic aberrations in mesenchymal stem cells of children with acute lymphoblastic leukemia

A novel PPARγ2 modulator sLZIP controls the balance between adipogenesis and osteogenesis during mesenchymal stem cell differentiation

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