Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential

Lojewski, Xenia; Srimasorn, Sumitra; Rauh, Juliane; Francke, Silvan; Wobus, Manja; Taylor, Verdon; Araúzo-Bravo, Marcos J.; Hallmeyer-Elgner, Susanne; Kirsch, Matthias; Schwarz, Sigrid C.; Schwarz, Johannes; Storch, Alexander; Hermann, Andreas

doi:10.5966/sctm.2015-0057

Cited by 19 publications

(16 citation statements)

References 38 publications

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“…During adipogenic and osteogenic differentiation, various mutations in LMNA gene which encodes for the nuclear lamin A/C protein influenced the differentiation efficacy of BM-MSCs in a mutation-specific manner and promoted unique gene expression patterns (Malashicheva et al, 2015). Comparative transcriptome analysis revealed that the adult human brain-derived perivascular MSCs holds comparable differential potential to that of the human brain-derived NSCs and the human BM-MSCs; thus highlighting the potential of perivascular MSCs for therapeutic use similar to neural and bone-marrow stem cells (Lojewski et al, 2015).…”

Section: Tracking Cell Differentiationmentioning

confidence: 95%

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Kasoju

Wang

Zhang

et al. 2017

Biotechnology Advances

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The plastic-adherent, fibroblast-like, clonogenic cells found in the human body now defined as multipotent "Mesenchymal Stromal Cells" (MSCs) hold immense potential for cell-based therapies. Recently, research and basic knowledge of these cells has fast-tracked, both from fundamental and translational perspectives. There have been important discoveries with respect to the available variety of tissue sources, the development of protocols for their easy isolation and in vitro expansion and for directed differentiation into various cell types. In addition, there has been discovery of novel abilities such as immune-modulation and further development of the use of biomaterials to aid isolation, expansion and differentiation together with improved delivery to the selected optimal tissue site. However, the molecular fingerprint of MSCs in these contexts remains imprecise and inadequate. Consequently, without this crucial knowledge it is difficult to achieve progress to determine with precision their practical developmental potentials. Detailed investigations on the global gene expression, or transcriptome, of MSCs could offer essential clues in this regard. In this article, we address the challenges associated with MSC transcriptome studies, the paradoxes observed in published experimental results and the need for careful transcriptomic analysis. We describe the exemplary applications with various transcriptome platforms that are used to address the variation in biomarkers and the identification of differentiation processes. The evolution and the potentials for adapting next-generation sequencing (NGS) technology in transcriptome analysis are discussed. Lastly, based on review of the existing understanding and published studies, we propose how NGS may be applied to promote further understanding of the biology of MSCs and their use in allied fields such as regenerative medicine.

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Section: Tracking Cell Differentiationmentioning

confidence: 95%

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Kasoju

Wang

Zhang

et al. 2017

Biotechnology Advances

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“…The relevance of MSCs for the bone marrow homeostasis is underpinned by the observation that co‐administration of autologous MSCs facilitated HSC engraftment after myeloablative treatments . Similarly, MSCs interact with tissue‐specific stem cells and functional parenchymal cells in various other organs including bone, lung and blood vessels …”

Section: Introductionmentioning

confidence: 99%

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

Rühle

Huber

Saffrich

et al. 2018

Intl Journal of Cancer

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Chemotherapeutic agents are part of the standard treatment algorithms for many malignancies; however, their application and dosage are limited by their toxic effects to normal tissues. Chemotherapy-induced toxicities can be long-lasting and may be incompletely reversible; therefore, causative therapies for chemotherapy-dependent side effects are needed, especially considering the increasing survival rates of treated cancer patients. Mesenchymal stem cells (MSCs) have been shown to exhibit regenerative abilities for various forms of tissue damage. Preclinical data suggest that MSCs may also help to alleviate tissue lesions caused by chemotherapeutic agents, mainly by establishing a protective microenvironment for functional cells. Due to the systemic administration of most anticancer agents, the effects of these drugs on the MSCs themselves are of crucial importance to use stem cell-based approaches for the treatment of chemotherapy-induced tissue toxicities. Here, we present a concise review of the published data regarding the influence of various classes of chemotherapeutic agents on the survival, stem cell characteristics and physiological functions of MSCs. Molecular mechanisms underlying the effects are outlined, and resulting challenges of MSC-based treatments for chemotherapy-induced tissue injuries are discussed.

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“…In addition, pericytes have been reported to possess multipotent potential, differentiating down the mesenchymal lineages in vitro . Recent reports have suggested that mesenchymal stromal cells (MSCs) may represent a subclass of pericytes following their identification in the perivascular tissue of almost all organs of the human body, including the adult brain . In vitro, MSCs, in addition to their multipotency are characterized by their capacity to exert strong immunosuppressive and trophic properties, mainly by the secretion of soluble factors .…”

Section: Introductionmentioning

confidence: 99%

Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination

Iacobaeus¹,

Sugars²,

Andrén³

et al. 2017

Stem Cells Translational Medicine

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Vascular changes, including blood brain barrier destabilization, are common pathological features in multiple sclerosis (MS) lesions. Blood vessels within adult organs are reported to harbor mesenchymal stromal cells (MSCs) with phenotypical and functional characteristics similar to pericytes. We performed an immunohistochemical study of MSCs/pericytes in brain tissue from MS and healthy persons. Post-mortem brain tissue from patients with early progressive MS (EPMS), late stage progressive MS (LPMS), and healthy persons were analyzed for the MSC and pericyte markers CD146, platelet-derived growth factor receptor beta (PDGFRb), CD73, CD271, alphasmooth muscle actin, and Ki67. The MS samples included active, chronic active, chronic inactive lesions, and normal-appearing white matter. MSC and pericyte marker localization were detected in association with blood vessels, including subendothelial CD146 1 PDGFRb 1 Ki67 1 cells and CD73 1 CD271 1 PDGFRb 1 Ki67 -cells within the adventitia and perivascular areas. Both immunostained cell subpopulations were termed mesenchymal perivascular cells (MPCs). Quantitative analyses of immunostainings showed active lesions containing increased regions of CD146 1 PDGFRb 1 Ki67 1 and CD73 1 CD271 1 PDGFRb 1 Ki67 -MPC subpopulations compared to inactive lesions. Chronic lesions presented with decreased levels of CD146 1 PDGFRb 1 Ki67 1 MPC cells compared to control tissue. Furthermore, LPMS lesions displayed increased numbers of blood vessels harboring greatly enlarged CD73 1 CD271 1 adventitial and perivascular areas compared to control and EPMS tissue. In conclusion, we demonstrate the presence of MPC subgroups in control human brain vasculature, and their phenotypic changes in MS brain, which correlated with inflammation, demyelination and MS disease duration. Our findings demonstrate that brain-derived MPCs respond to pathologic mechanisms involved in MS disease progression and suggest that vessel-targeted therapeutics may benefit patients with progressive MS. STEM CELLS TRANSLATIONAL MEDICINE 2017;6:1840-1851 SIGNIFICANCE STATEMENTThis immunohistochemical study characterized vascular cells phenotypically similar to pericytes and mesenchymal stromal cells (MSCs) in brain tissue of multiple sclerosis (MS) and healthy persons. We found variations in phenotype, distribution, and proliferation of cells co-expressing markers for MSCs and pericytes that associated with inflammation and MS disease duration. Tissue from long standing MS presented with increased numbers of blood vessels that harbored expanded perivascular areas of cells staining positive for MSCs/pericyte markers. This is the first study to show involvement of MSC/pericyte phenotypic changes in MS pathology and highlights that vessel-targeted treatments may benefit late stage MS.

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Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential

Cited by 19 publications

References 38 publications

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

Transcriptomics of human multipotent mesenchymal stromal cells: Retrospective analysis and future prospects

The current understanding of mesenchymal stem cells as potential attenuators of chemotherapy‐induced toxicity

Dynamic Changes in Brain Mesenchymal Perivascular Cells Associate with Multiple Sclerosis Disease Duration, Active Inflammation, and Demyelination

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