Co‐culture with mesenchymal stromal cells increases proliferation and maintenance of haematopoietic progenitor cells

Walenda, Thomas; Bork, Simone; Horn, Patrick; Wein, Frederik; Saffrich, Rainer; Diehlmann, Anke; Eckstein, Volker; Ho, Anthony D.; Wagner, Wolfgang

doi:10.1111/j.1582-4934.2009.00776.x

Cited by 152 publications

(128 citation statements)

References 74 publications

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“…[15][16][17][18][19] Furthermore, replicative senescence affects the ability of MSC to support hematopoieisis. 20 We observed that MSC cultured with adult pHPL ceased proliferation after fewer than 50 PD, whereas more than 60 PD were possible in FBS-driven cultures. 21 It remains unclear whether common senescence-associated gene expression changes are induced in MSC that have been isolated using different isolation and culture methods.…”

Section: Introductionmentioning

confidence: 85%

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Schallmoser¹,

Bartmann²,

Rohde³

et al. 2010

Haematologica

108

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BackgroundResearch on mesenchymal stromal cells has created high expectations for a variety of therapeutic applications. Extensive propagation to yield enough mesenchymal stromal cells for therapy may result in replicative senescence and thus hamper long-term functionality in vivo. Highly variable proliferation rates of mesenchymal stromal cells in the course of long-term expansions under varying culture conditions may already indicate different propensity for cellular senescence. We hypothesized that senescence-associated regulated genes differ in mesenchymal stromal cells propagated under different culture conditions. Design and MethodsHuman bone marrow-derived mesenchymal stromal cells were cultured either by serial passaging or by a two-step protocol in three different growth conditions. Culture media were supplemented with either fetal bovine serum in varying concentrations or pooled human platelet lysate. ResultsAll mesenchymal stromal cell preparations revealed significant gene expression changes upon long-term culture. Especially genes involved in cell differentiation, apoptosis and cell death were up-regulated, whereas genes involved in mitosis and proliferation were down-regulated. Furthermore, overlapping senescence-associated gene expression changes were found in all mesenchymal stromal cell preparations. ConclusionsLong-term cell growth induced similar gene expression changes in mesenchymal stromal cells independently of isolation and expansion conditions. In advance of therapeutic application, this panel of genes might offer a feasible approach to assessing mesenchymal stromal cell quality with regard to the state of replicative senescence.

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Section: Introductionmentioning

confidence: 85%

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Schallmoser¹,

Bartmann²,

Rohde³

et al. 2010

Haematologica

108

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“…[41][42][43] MSC senescence influences not only differentiation potential but also the support of hematopoiesis. 44 To date, knowledge regarding the role of MSC senescence in hematopoietic support is limited. In this study, other than the classic feature of cellular senescence, Dicer1-KD MSC showed a significantly reduced capacity to support CD34 + cells in LTC-IC assays.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of Dicer1 promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells in patients with myelodysplastic syndrome

Zhao¹,

Wu²,

Fei³

et al. 2014

Haematologica

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ABSTRACTdence suggests that microRNA (miRNA, miR) are functionally involved in MSC senescence. [18][19][20] The ablation of Dicer1 (an RNAse III endonuclease essential for miRNA biogenesis) and the loss of mature miRNA in embryonic fibroblasts and endothelial cells inhibited cell proliferation and induced a premature senescence phenotype. 21,22 Although recent striking findings indicate that Dicer1 deletion can induce an MDS phenotype in mice 23 and that Dicer1 expression is reduced in MSC from MDS patients, 24 the precise mechanism by which the Dicer1 gene contributes to the pathogenesis of MDS remains elusive. We inferred that disordered expression of Dicer1 could contribute to abnormal MSC senescence and impaired stromal support in MDS.The aims of this study were, therefore, to evaluate the senescent features of BM-MSC from patients with MDS and to explore the role of Dicer1 in the senescence of MSC and the disturbed stromal function observed in patients with MDS. Methods Patients and control samplesA total of 77 patients with MDS were included in this study. Their characteristics are detailed in Online Supplementary Table S1. Patients were diagnosed with MDS according to the minimum diagnostic criteria established by the Conference on MDS. 25Patients were classified for the study as "lower-risk" (LR) [International Prognostic Scoring System (IPSS) low/int-1] and as "higher-risk" (HR) (IPSS-int-2/high).26 Twenty-two healthy volunteers were used as controls (median age 62 years; age range, 43-78 years) and were matched for gender and age. All study participants signed an informed consent form. The research was approved by the ethics committee of the Sixth Hospital affiliated with Shanghai Jiao Tong University, and all patient-relevant research strictly abided by the Declaration of Helsinki. Mesenchymal stromal cell characterizationBM-MSC were isolated and cultured; their immunophenotype, clonogenic and proliferative potential, and differentiation were studied and SA-β-Gal assay were performed. Detailed information about the experiments is provided in the Online Supplementary Material. RNA isolation and real-time polymerase chain reaction analysisTotal RNA was isolated using TRIzol (Invitrogen, Paisley, Scotland) according to the manufacturer's instructions. For mRNA detection, the RNA was reverse transcribed using the RevertAid First Strand cDNA Synthesis Kit (Fermentas, Burlington, Canada) according to the manufacturer's protocol, and real-time polymerase chain reaction (RT-PCR) was performed using RealMasterMix (Takara, Dalian, China). The process used was described in detail in our previous study. 27 The primers are listed in Online Supplementary Table S2. RT-PCR for miRNA was performed using the PrimeScript ™ miRNA qPCR Starter Kit Ver. 2.0 (Takara, Dalian, China). RNU6B was used as the housekeeping gene. Fold change was calculated using the DDCT method of relative quantification. Isolation of CD34 + cells and CD271 + cellsMononuclear cells were obtained from BM aspirates by density gradient separation and...

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“…75 These functional changes are accompanied by continuous changes in their gene expression profile 76 and DNA-methylation pattern. 77 Furthermore, miRNA expression profiles vary in the course of culture expansion 78,79 and these may contribute to the supportive hematopoiesis function of MSC.…”

Section: Mirnas In the Hematopoietic Stem Cell Nichementioning

confidence: 99%

MicroRNAs are shaping the hematopoietic landscape

Bissels¹,

Bosio²,

Wagner³

2011

Haematologica

115

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Co‐culture with mesenchymal stromal cells increases proliferation and maintenance of haematopoietic progenitor cells

Cited by 152 publications

References 74 publications

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Replicative senescence-associated gene expression changes in mesenchymal stromal cells are similar under different culture conditions

Down-regulation of Dicer1 promotes cellular senescence and decreases the differentiation and stem cell-supporting capacities of mesenchymal stromal cells in patients with myelodysplastic syndrome

MicroRNAs are shaping the hematopoietic landscape

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