Efficacy of Bone Marrow Mononuclear Cells to Promote Bone Regeneration Compared With Isolated CD34+ Cells From the Same Volume of Aspirate

Abstract Abstract 3857 The diagnosis of patients with myelodysplastic syndromes (MDS) is largely dependent on morphologic examination of bone marrow aspirates. Several criteria that form the basis of the classifications and scoring systems most commonly used in clinical practice are affected by operator-dependent variation. In order to identify more standardized molecular markers that would allow a more reliable prediction of prognosis, we have used gene expression profiling (GEP) data on CD34+ cells from MDS patients to determine the relationship between gene expression levels and prognosis in this disorder. GEP data on CD34+ cells from 125 MDS patients with a minimum 12-month follow-up since date of bone marrow sample collection were included in this study. Prediction for overall survival was performed using supervised principal components (“SuperPC”) and lasso penalized Cox proportional hazards regression applying the “Coxnet” algorithm. Supervised principal components analysis was performed on patients randomly split in a training set (n=84) and a test set (n=41), and 139 genes were identified the expression of which was significantly associated with MDS patient survival, including LEF1, CDH1, WT1 and MN1. In order to identify a smaller set of genes associated with patient survival, a second approach aiming at building sparse prediction models was used. A model was generated using the Coxnet algorithm and a predictor consisting of 20 genes was identified. Eight genes identified by the supervised principal components method were in common with the genes identified by the Coxnet model: ADHFE1, BTBD6, CPT1B, LEF1, FRMD6, GPR114, C7orf58 and LOC100286844. The Coxnet predictor outperformed other predictors including one which additionally used clinical information. To validate our findings, we evaluated the performance of our prognostic Coxnet gene signature in an independent gene expression profiling dataset on MDS bone marrow mononuclear cells (Mills et al, Gene Expression Omnibus series GSE15061). Our Coxnet gene signature based on CD34+ cells significantly identified a low-risk patient group in this independent GEP dataset based on unsorted bone marrow mononuclear cells, demonstrating that our signature is robust and may be applicable to bone marrow cells without the need to isolate CD34+ cells. These GEP-based signatures correlating with clinical outcome may significantly contribute to a refined risk classification of MDS. Disclosures: No relevant conflicts of interest to declare.

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Neovascularization and bone regeneration by implantation of autologous bone marrow mononuclear cells

Biomaterials ◽

10.1016/j.biomaterials.2004.11.032 ◽

2005 ◽

Vol 26 (22) ◽

pp. 4550-4556 ◽

Cited By ~ 52

Author(s):

Takashi Hisatome ◽

Yuji Yasunaga ◽

Shinobu Yanada ◽

Yasuhiko Tabata ◽

Yoshito Ikada ◽

...

Keyword(s):

Bone Marrow ◽

Bone Regeneration ◽

Mononuclear Cells ◽

Autologous Bone Marrow ◽

Bone Marrow Mononuclear Cells ◽

Autologous Bone

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The effect of bone marrow mononuclear cells on vascularization and bone regeneration in steroid-induced osteonecrosis of the femoral head

Joint Bone Spine ◽

10.1016/j.jbspin.2009.04.002 ◽

2009 ◽

Vol 76 (6) ◽

pp. 685-690 ◽

Cited By ~ 46

Author(s):

Yuan Sun ◽

Yong Feng ◽

Changqing Zhang

Keyword(s):

Bone Marrow ◽

Femoral Head ◽

Bone Regeneration ◽

Mononuclear Cells ◽

Bone Marrow Mononuclear Cells

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Effect of erythropoietin on bone marrow mononuclear cells

Medical Immunology (Russia) ◽

10.15789/1563-0625-eeo-1807 ◽

2020 ◽

Vol 22 (1) ◽

pp. 135-142

Author(s):

A. P. Lykov ◽

M. A. Surovtseva ◽

O. V. Poveshchenko ◽

A. M. Chernyavsky ◽

A. V. Fomichev ◽

...

Keyword(s):

Cell Cycle ◽

Stem Cells ◽

Bone Marrow ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Mononuclear Cells ◽

Proliferative Potential ◽

Bone Marrow Mononuclear Cells ◽

Short Term ◽

Cd34 Cells

Stem/progenitor cells are considered an alternative method of heart failure therapy by promoting regeneration of damaged myocardium in myocardial infarction. Effectiveness of cell therapy depends on the population composition and functional activity of the cell graft, and, in turn, it depends on the conditions of microenvironment. Cultivation of stem/progenitor cells with erythropoietin stimulates proliferative potential causing in vitro resistance to hypoxia, and in vivo stimulation of angiogenesis. We aimed for assessing effects of erythropoietin upon hematopoietic cells. We studied some effects of short-term incubation of bone marrow mononuclear cells (BM-MNCs) in patients with coronary heart disease (CHD) with erythropoietin upon cellular phenotype, cell cycle, apoptosis and their proliferative potential. BM-MNCs were isolated from bone marrow aspirate from patients with CHD in a density gradient, then incubated for 60 minutes with erythropoietin (33.4 IU/ml). Using flow cytometric assay of the total BM-MNCs pool, we have shown there endothelial progenitor cells at different stages of maturation and differentiation, mesenchymal stem cells are. Their total number did not exceed 30%. Short-term incubation of BM-MNCs with erythropoietin reduces expression of CD184 “homing receptor” molecules on CD34+ cells, and causes increase of CD184 on CD31+ cells in the BM-MNCs pool (p < 0.05). In addition, erythropoietin has been shown to cause a delay of CD34+ cells in the resting phase (G0G1), reduce a proportion of cells in the synthetic phase (S) and mitosis (G2/M) (p<0.05), and does not affect apoptosis, as shown by Annexin V-FITC Apoptosis Detection Kit. Erythropoietin had no significant effects on expression on BM-MNCs surface molecules involved in providing adhesion, such as CD18, CD29, CD44, CD49a, CD54, CD62E, CD146, and CD202b. MTT-method has shown that the short-term preincubation of BM-MNCs with erythropoietin contributed to a significant decrease in proliferative activity of BM-MNCs (p < 0.05). However, there was a tendency towards increased resistance of erythropoietin-pretreated BM-MNCs to oxidative stress induced by hydrogen peroxide. We have also revealed a correlation between the numbers of endothelial progenitor cells at different stages of differentiation, and numbers of hematopoietic stem cells in the total BM-MNCs pool. The number of CD34+/CD133+, CD34- / CD31+, CD45+/EpoR+, and CD34+/EpoR+ in BM-MNCs pool are dependent on the age of patients. Hence, a short-term incubation of BM-MNCs with erythropoietin promotes the cells to be retained in resting phase of the cell cycle, thus, in turn, helping to reduce proliferative potential of BM-MNCs.

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