Characteristics of Mesenchymal Stem Cells under Hypoxia

Amorin, Bruna; Alegretti, Ana Paula; Valim, Vanessa de Souza; Silva, Annelise Martins Pezzi da; Silva, Maria Aparecida Lima da; Sehn, Filipe; Silla, Lúcia Mariano da Rocha

doi:10.4236/cellbio.2013.21002

Cited by 4 publications

(2 citation statements)

References 73 publications

(132 reference statements)

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“…The relationship between BMAT and hypoxia is likely an important, dynamic, and bidirectional relationship that contributes to MM development and drug resistance. As oxygen tension ranges from 21 (in normoxia) to 12% in peripheral blood and ~1.3 to 3% (hypoxia) in the BM, based on the proximity to the vasculature and endosteum ( 120 ), it is probable that BMAT-MM in vitro experiments, and perhaps all BM cultures, will give more translational data if they are performed in hypoxic rather normoxic conditions ( 121 ). This is because hypoxia can drive proliferation of stem cells via HIF1 signaling ( 122 ), induce drug resistance in MM cells, and affect MM cell homing and egress from the BM ( 123 – 126 ).…”

Section: Bone Marrow Adipocyte Influences On MMmentioning

confidence: 99%

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

2016

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In the year 2000, Hanahan and Weinberg (1) defined the six Hallmarks of Cancer as: self-sufficiency in growth signals, evasion of apoptosis, insensitivity to antigrowth mechanisms, tissue invasion and metastasis, limitless replicative potential, and sustained angiogenesis. Eleven years later, two new Hallmarks were added to the list (avoiding immune destruction and reprograming energy metabolism) and two new tumor characteristics (tumor-promoting inflammation and genome instability and mutation) (2). In multiple myeloma (MM), a destructive cancer of the plasma cell that grows predominantly in the bone marrow (BM), it is clear that all these hallmarks and characteristics are in play, contributing to tumor initiation, drug resistance, disease progression, and relapse. Bone marrow adipose tissue (BMAT) is a newly recognized contributor to MM oncogenesis and disease progression, potentially affecting MM cell metabolism, immune action, inflammation, and influences on angiogenesis. In this review, we discuss the confirmed and hypothetical contributions of BMAT to MM development and disease progression. BMAT has been understudied due to technical challenges and a previous lack of appreciation for the endocrine function of this tissue. In this review, we define the dynamic, responsive, metabolically active BM adipocyte. We then describe how BMAT influences MM in terms of: lipids/metabolism, hypoxia/angiogenesis, paracrine or endocrine signaling, and bone disease. We then discuss the connection between BMAT and systemic inflammation and potential treatments to inhibit the feedback loops between BM adipocytes and MM cells that support MM progression. We aim for researchers to use this review to guide and help prioritize their experiments to develop better treatments or a cure for cancers, such as MM, that associate with and may depend on BMAT.

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Section: Bone Marrow Adipocyte Influences On MMmentioning

confidence: 99%

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

2016

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“…Mesenchymal stem cells (MSCs), also referred to mesenchymal stromal cells, are considered as non-hematopoietic multipotent stem cells with self-renewal properties and ability to differentiate into mesoderm tissues. MSCs were first described by Friedenstein et al in the 1970s, as cells morphologically similar to fibroblasts and with a high ability to adhere to plastic surfaces [1]. MSC must express CD105, CD73 and CD90, and lack expression of CD45, CD34, CD14 or CD11b, CD79a or CD19 and HLA-DR surface molecules.…”

Section: Introductionmentioning

confidence: 99%

Optimization of the Cultivation of Donor Mesenchymal Stromal Cells for Clinical Use in Cellular Therapy

Valim¹,

Amorin²,

Pezzi³

et al. 2014

CellBio

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Mesenchymal stromal cells (MSC) have shown their benefits in graft-versus-host disease (GVHD), with five unsettled matters: 1) MSCs expansion in medium with Fetal Bovine Serum (FBS) and its risk of xenoreaction;2) The number of cells indicated for therapy that is relatively high, with the need to optimize the expansion, number and time wise; 3) The utilization of third party donors; 4) Culture passage number (P); and 5) Source of the cells. This study was designed to determine the superiority of the Platelet Lysates (PL) over FBS on the expansion of MSC, the optimal cell' plating density and days between each pass, and to investigate if donor total nucleated cells (TNC) obtained from the washouts of discharged bags and filters of hematopoietic stem cell transplantation (HSCT) can be expanded to be used at clinical grade. TNC were removed, plated and after the first passage were cultivated in different concentrations with FBS or PL, and the number of days to reach 80% of confluence was observed. Next, cultures with the same plating density were fed either with PL or with FBS and after seven days counted to analyze how much they had grown in that period. The proliferation of mesenchymal stromal cells in the presence of PL and SFB was averaged 11.88 and 2.5 times, respectively, in a period of 7 days. The highest concentration of plating cells using PL took less time to reach confluence as compared with the three lower ones. This study suggests that the PL is the best choice as a supplement to expand MSC and to allow the proliferation of enough number of MSC at P2 for clinical use. KeywordsPlatelet Lysate; MSC, Optimization; Cell Therapy V. Valim et al. 26

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Aldehyde Dehydrogenase Activity in Adipose Tissue: Isolation and Gene Expression Profile of Distinct Sub-population of Mesenchymal Stromal Cells

Najar

Crompot

Grunsven

et al. 2018

Stem Cell Rev and Rep

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Thanks to their relative abundance and easier collection, adipose tissue (AT) is considered an alternative source for the isolation of mesenchymal stromal cells (MSCs). MSCs have great therapeutic values and are thus under investigations for several clinical indications such as regenerative medicine and immunomodulation. In this work, we aimed to identify, isolate and characterize AT-MSCs based on their aldehyde dehydrogenase (ALDH) activity known to be a classical feature of stem cells. FACS technology allowed to isolate two different populations of AT-MSCs according to their ALDH activity (referred as ALDH and ALDH). Depending on their ALDH activity, the transcriptome analysis of both cell populations demonstrated a differential pattern of genes related to the main properties of MSCs (proliferation, response to hypoxia, angiogenesis, phenotype, stemness, multilineage, hematopoiesis, immunomodulation). Based on these profiling, both AT-MSC populations could differ in terms of biological responses and functionalities. Collectively, the use of ALDH for isolating and identifying sub-populations of MSCs with specific gene profile may represent an alternative method to provide solutions for targeted therapeutic applications.

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Characteristics of Mesenchymal Stem Cells under Hypoxia

Cited by 4 publications

References 73 publications

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

Signaling Interplay between Bone Marrow Adipose Tissue and Multiple Myeloma cells

Optimization of the Cultivation of Donor Mesenchymal Stromal Cells for Clinical Use in Cellular Therapy

Aldehyde Dehydrogenase Activity in Adipose Tissue: Isolation and Gene Expression Profile of Distinct Sub-population of Mesenchymal Stromal Cells

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