Leptin receptor/CD295 is upregulated on primary human mesenchymal stem cells of advancing biological age and distinctly marks the subpopulation of dying cells

Laschober, Gerhard; Brunauer, Regina; Jamnig, Angelika; Fehrer, Christine; Greiderer, Brigitte; Lepperdinger, Günter

doi:10.1016/j.exger.2008.05.013

Cited by 38 publications

(31 citation statements)

References 29 publications

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“…In the adult bone marrow (BM), the LEPR identifies medullary mesenchymal stem cells (MSCs) 18 as well as pericyte-like stromal cells that support hematopoiesis within the vascular niche 19–21 . Upregulation of the LEPR gene in cultured BM-MSCs has been associated with cessation of growth due to replicative senescence 22 . Two recent studies showed that hypoxia-preconditioned murine BM-MSCs exert enhanced regenerative actions through an amplification of the LEP signalling 23, 24 .…”

Section: Introductionmentioning

confidence: 99%

The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

Riu

Slater

García

et al. 2017

Sci Rep

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Transplantation of adventitial pericytes (APCs) improves recovery from tissue ischemia in preclinical animal models by still unknown mechanisms. This study investigates the role of the adipokine leptin (LEP) in the regulation of human APC biological functions. Transcriptomic analysis of APCs showed components of the LEP signalling pathway are modulated by hypoxia. Kinetic studies indicate cultured APCs release high amounts of immunoreactive LEP following exposure to hypoxia, continuing upon return to normoxia. Secreted LEP activates an autocrine/paracrine loop through binding to the LEP receptor (LEPR) and induction of STAT3 phosphorylation. Titration studies using recombinant LEP and siRNA knockdown of LEP or LEPR demonstrate the adipokine exerts important regulatory roles in APC growth, survival, migration and promotion of endothelial network formation. Heterogeneity in LEP expression and secretion may influence the reparative proficiency of APC therapy. Accordingly, the levels of LEP secretion predict the microvascular outcome of APCs transplantation in a mouse limb ischemia model. Moreover, we found that the expression of the Lepr gene is upregulated on resident vascular cells from murine ischemic muscles, thus providing a permissive milieu to transplanted LEP-expressing APCs. Results highlight a new mechanism responsible for APC adaptation to hypoxia and instrumental to vascular repair.

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Section: Introductionmentioning

confidence: 99%

The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

Riu

Slater

García

et al. 2017

Sci Rep

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“…16 We approached these problems by comparing wholegenome gene expression profiles of primary MSCs from differently aged, healthy individuals. We concentrated primarily on differentially expressed genes that encode known proteins that are presented at the outer cell surface 40 ; suffice it to say that antibodies that are commercially available to detect such factors would ease any subsequent functional characterization. One of the candidates emerging from the wealth of genomic data is VCAM-1/CD106.…”

Section: Age-related Changes In Mesenchymal Stem Cells 125mentioning

confidence: 99%

Age-Specific Changes of Mesenchymal Stem Cells Are Paralleled by Upregulation of CD106 Expression As a Response to an Inflammatory Environment

Laschober

Brunauer

Jamnig

et al. 2011

Rejuvenation Research

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Regeneration, tissue remodeling, and organ repair after injury, which rely on the regulated activity of tissue-borne stem cells, become increasingly compromised with advancing age. Mesenchymal stroma cells were isolated from bone of differently aged healthy donors. The rare population of mesenchymal stem cells (MSCs) contained in the primary cell isolates barely declined in number, yet the stem cells displayed diminished long-term proliferation potential relative to the donor age and the expression of vascular cell adhesion molecule-1 (VCAM-1; CD106) was elevated on primary MSCs. In CD106(bright) MSCs, the abundance of a panel of stemness transcription factors remained unchanged. Because the CD106 level could be further enhanced by proinflammatory cytokines, we considered the rate of VCAM-1 expression to be a good reflection of an endogenous inflammatory milieu to which the MSCs are exposed. Treatment of MSCs with increasing doses of interferon-γ exerted no immediate influence on their self-renewal capacity. However, it impacted on the differentiation potential toward the adipogenic or osteogenic lineage. Moderately elevated levels of inflammatory stimuli supported osteoblastogenesis whereas the same treatment reduced adipogenic differentiation in MSCs from young and intermediately aged donors. In MSCs from elderly donors, however, osteoblastogenesis was greatly diminished in an inflammatory environment whereas adipogenic differentiation remained unchanged. Conclusively, moderate levels of inflammatory stimuli are being interpreted by MSCs at a young age as instructive signals for osteoblastogenesis, whereas at old age, an inflammatory milieu may effectively suppress bone remodeling and repair by tissue-borne MSCs while uninterrupted adipogenic differentiation may lead to adipose upgrowth.

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“…This fits in line with low oxygen tension culturing being beneficial. Furthermore, LEPR mRNA levels could be used as a measure of stem cell ageing to help find more tactics to beat stem cell senescence [24]. …”

Section: Effects Of Donor Stem Cell Age On Cell Replication and Diffementioning

confidence: 99%

Advances and Developments in the Use of Human Mesenchymal Stem Cells – A Few Considerations

Kennard¹

2011

TOORHTJ

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One less visited area in musculoskeletal stem cell research is the effects of donor age on quality of stem cells. The prevalence of degenerative orthopaedic conditions is large, and the older population is likely to receive great benefit from stem cell therapies. There are many known growth factors involved in controlling and influencing stem cell growth which are also related to cell senescence. Of which, expressions are found to be altered in mesenchymal stem cells from older donors. Considerations must also be taken of these mechanisms which also have a role in cell cycle and tumour suppression.

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Leptin receptor/CD295 is upregulated on primary human mesenchymal stem cells of advancing biological age and distinctly marks the subpopulation of dying cells

Cited by 38 publications

References 29 publications

The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

Age-Specific Changes of Mesenchymal Stem Cells Are Paralleled by Upregulation of CD106 Expression As a Response to an Inflammatory Environment

Advances and Developments in the Use of Human Mesenchymal Stem Cells – A Few Considerations

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