Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche

Tian, Lei; Wu, Yaojiong

doi:10.1155/2011/353878

Cited by 72 publications

(55 citation statements)

References 100 publications

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“…Accordingly, the expression of two cytokines, G-CSF and vascular endothelial growth factor were significantly down-regulated in Dicer1-KD MSC. These molecules are involved in the regulation of hematopoiesis, 45,46 suggesting that their deregulation contributes to the impaired support of hematopoiesis characteristic of Dicer1-KD MSC. It is worth mentioning that the level of G-CSF expression has been reported to be decreased in MDS-MSC.…”

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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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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“…They can differentiate along multiple lineages and exhibit significant expansion capability in vitro. Co-transplantation with MSCs improves engraftment of HSCs after autologous intra-bone marrow transplantation [3]. MSCs are also considered useful as vehicles for emerging cell and gene therapies in the field of tissue engineering [4].…”

Section: Introductionmentioning

confidence: 99%

“…MSCs are also considered useful as vehicles for emerging cell and gene therapies in the field of tissue engineering [4]. Recently it has been postulated that MSC provide the conducive microenvironment for HSCs and thus maintain the stemness and proliferation of HSCs and support HSC transplantation [3].…”

Section: Introductionmentioning

confidence: 99%

Pluripotent Stem Cells in Bone Marrow and Cord Blood

Shaikh¹,

Bhartiya²

2012

Blood Cell - An Overview of Studies in Hematology

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“…MSCs have been demonstrated to support long-term growth of HSCs hematopoietic stem cells and maintain hematopoietic and skeletal homeostasis [2]. Previous studies showed MSCs transplantation resulted in improvement of diabetes conditions, such as reducing blood glucose levels [3][4][5], partially because of the immunosuppressive effects of MSCs on T cells, increasing pancreatic islet β cell mass, preventing of β cell death [6] and promoting islet regeneration [7].…”

Section: Introductionmentioning

confidence: 99%

Regulation of blood glucose by administration of allogenic bone marrow derived mesenchymal stem cells into diabetic rats through modulating regeneration of both α and β islet cells

Meng¹,

Liu²,

Li³

et al. 2013

J Diab Res Clin Met

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Background: Transplanting bone marrow derived mesenchymal stem cells(MSCs) have positive effects in treating many disease conditions including diabetes. To investigate the effects of systemic administration of MSCs on blood glucose changes, we studied the changes of islet β and α cellsin STZ-induced diabetic rats following systemic MSCs administration. Methods: MSCs were isolated from rat bone marrow, characterized, expanded in vitro and labeled with GFP by lentivirus transfection. 2x106 MSCs were injected into the rats via caudal vein at 10 days following STZ administration. The fasting glucose serum levels were measured following the treatment. Animals were terminated at day 21 and 35 following STZ injection. The insulin, Pdx1, glucagon and somatoatatin expressing cells in the pancreatic sections were quantified by immunofluorescence methods. Results: We found that the blood glucose levels in the rats receiving MSCs were significantly reduced compared to the control group at day 21 following STZ treatment, and it reached to the similar high glucose level again at day 28. The injected MSCs were found in the pancreatic tissues, and the islets in the treatment group were partially restored in contrast to the control group. There were greater numbers of Pdx1+Insulin− cells in the MSCs treatment group, suggesting the ongoing regeneration of islet. The number of α cellswas significantly higher in the MSCs-treated group and untreated control group than that of normal group, which may associate with higher blood glucose level in later stage of MSCs administration. In addition, MSCs were co-cultured with the isolated rat islets and islet-like cells (INS1) in vitro and we found that the expression of Cdk4 was up-regulated in the islets when co-cultured with MSCs. Conclusions: We concluded that transplanting allogenic MSCs may promote the regeneration of the injured islets, but the underlying mechanisms need further investigation.

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Paracrine Molecules of Mesenchymal Stem Cells for Hematopoietic Stem Cell Niche

Cited by 72 publications

References 100 publications

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

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

Pluripotent Stem Cells in Bone Marrow and Cord Blood

Regulation of blood glucose by administration of allogenic bone marrow derived mesenchymal stem cells into diabetic rats through modulating regeneration of both α and β islet cells

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