scholarly journals Comparing the Gene Expression Profile of Stromal Cells from Human Cord Blood and Bone Marrow: Lack of the Typical “Bone” Signature in Cord Blood Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Julia Bosch ◽  
Amelie Pia Houben ◽  
Tatiana Hennicke ◽  
René Deenen ◽  
Karl Köhrer ◽  
...  

With regard to the bone-regenerative capacity, bone marrow stromal cells (BMSC) can still be termed the “gold standard.” Nevertheless, neonatal stromal cells from cord blood (CB) feature advantages concerning availability, immaturity, and proliferation potential. The detailed gene expression analysis and overexpression of genes expressed differentially provide insight into the inherent capacity of stromal cells. Microarray and qRT-PCR analyses revealed closely related gene expression patterns of two stromal cell populations derived from CB. In contrast to the CB-derived cell types, BMSC displayed high expression levels ofBSP,OSX,BMP4,OC, andPITX2. Lentiviral overexpression ofBSPbut not ofOSXin CB-cells increased the capacity to form a mineralized matrix.BMP4induced the secretion of proteoglycans during chondrogenic pellet culture and extended the osteogenic but reduced the adipogenic differentiation potential. BMSC revealed the typical osteogenic gene expression signature. In contrast, the CB-derived cell types exhibited a more immature gene expression profile and no predisposition towards skeletal development. The absence ofBSPandBMP4—which were defined as potential key players affecting the differentiation potential—in neonatal stromal cells should be taken into consideration when choosing a cell source for tissue regeneration approaches.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2490-2490
Author(s):  
Paola Neri ◽  
Pierfrancesco Tassone ◽  
Masood A. Shammas ◽  
Daniel R. Carrasco ◽  
Renate Burger ◽  
...  

Abstract Multiple Myeloma (MM) cells interact with bone marrow (BM) microenvironment leading to induction of adhesion-mediated and cytokine mediated cell signalling which plays a critical role in promoting MM cell growth, survival, migration and development of drug resistance. We have previously evaluated gene expression changes following interaction between MM cells and BM stromal cells in vitro. However, the interaction between MM cells and microenvironment cells within the bone marrow is unique and its understanding is critical in evaluating effects of novel agents. We here describe a unique model that allows us to analyse in vivo expression changes in MM cells within the human BM milieu; and present preliminary results of expression changes following these in vivo interactions. In this model, BM stromal and IL-6-dependent human MM cell line INA-6 tranduced with GFP (green fluorescent protein) was injected in human fetal bone chip transplanted into SCID mice (SCID-hu mice). The MM cells were allowed to interact with the bone marrow for variable length of time, the bone chip was then retrieved, cells flashed out and GFP+ MM cells were separated by flow cytometry. The GFP negative fraction, containing stromal elements was also separated. Similar flow isolation process was used on INA-6GFP+ cells cultured in vitro and used as control. Total RNA was isolated from these cells and gene expression profile analyzed using the HG-U133 array chip (Affimetrix). We report that interaction between INA-6 cells and the BM microenvironment in vivo induced significant changes in expression profile. In particular, we observed up-regulation of genes implicated in regulation of cell proliferation (RGS 1 and 2, FOS, FOSB, S100A4); DNA transcription (AP1, SWI/SNF related member 1); chromosome organization (Histone1, 2 and 3); cellular trafficking and transport (ARFGEF2, Aquarin 3 and ATPase 4B); and signal transduction (Chemokine ligand 2, 3 and 15, Chemokine receptor 1, 2 and 4, Dual specificity phosphatase 1 and 4, Protein tyrosine phosphatase 1, PIP5-kinase 1A and ZAP70). We also observed down-regulation of genes involved in apoptosis (BCL2-interacting killer, APC, E1A binding protein p300, Fas-associated via death domain, Caspase-activated Dnase, Raf1); and cell-cell adhesion molecules (Cadherin 15, Leupakin, Neurekin, CD44, ICAM2 and PECAM-1a). Although some similarities were observed in gene profile changes following in vitro and in vivo interaction with microenvironment cells, differences were also found. We are now evaluating the effects of interaction on expression profile of stromal cells as well as duration of interaction. Taken together these data confirm the ability of BM microenvironment to modulate gene expression profile of the MM cells in vivo to mediate the MM cell growth, survival and migration. This model now provides us with an opportunity to study effects of novel agents on MM cells expression profile in vivo to pre-clinically characterize their activity.


2003 ◽  
Vol 311 (2) ◽  
pp. 227-237 ◽  
Author(s):  
Georg Wieczorek ◽  
Christine Steinhoff ◽  
Ralph Schulz ◽  
Marina Scheller ◽  
Martin Vingron ◽  
...  

2020 ◽  
Vol 319 (2) ◽  
pp. L197-L210 ◽  
Author(s):  
Stefanie Noel Sveiven ◽  
Tara M. Nordgren

Until recently, data supporting the tissue-resident status of mesenchymal stromal cells (MSC) has been ambiguous since their discovery in the 1950–60s. These progenitor cells were first discovered as bone marrow-derived adult multipotent cells and believed to migrate to sites of injury, opposing the notion that they are residents of all tissue types. In recent years, however, it has been demonstrated that MSC can be found in all tissues and MSC from different tissues represent distinct populations with differential protein expression unique to each tissue type. Importantly, these cells are efficient mediators of tissue repair, regeneration, and prove to be targets for therapeutics, demonstrated by clinical trials ( phase 1– 4) for MSC-derived therapies for diseases like graft-versus-host-disease, multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. The tissue-resident status of MSC found in the lung is a key feature of their importance in the context of disease and injuries of the respiratory system, since these cells could be instrumental to providing more specific and targeted therapies. Currently, bone marrow-derived MSC have been established in the treatment of disease, including diseases of the lung. However, with lung-resident MSC representing a unique population with a different phenotypic and gene expression pattern than MSC derived from other tissues, their role in remediating lung inflammation and injury could provide enhanced efficacy over bone marrow-derived MSC methods. Through this review, lung-resident MSC will be characterized, using previously published data, by surface markers, gene expression patterns, and compared with bone-marrow MSC to highlight similarities and, importantly, differences in these cell types.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Marie-Theresa Weickert ◽  
Judith S. Hecker ◽  
Michèle C. Buck ◽  
Christina Schreck ◽  
Jennifer Rivière ◽  
...  

AbstractMyelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell disorders with a poor prognosis, especially for elderly patients. Increasing evidence suggests that alterations in the non-hematopoietic microenvironment (bone marrow niche) can contribute to or initiate malignant transformation and promote disease progression. One of the key components of the bone marrow (BM) niche are BM stromal cells (BMSC) that give rise to osteoblasts and adipocytes. It has been shown that the balance between these two cell types plays an important role in the regulation of hematopoiesis. However, data on the number of BMSC and the regulation of their differentiation balance in the context of hematopoietic malignancies is scarce. We established a stringent flow cytometric protocol for the prospective isolation of a CD73+ CD105+ CD271+ BMSC subpopulation from uncultivated cryopreserved BM of MDS and AML patients as well as age-matched healthy donors. BMSC from MDS and AML patients showed a strongly reduced frequency of CFU-F (colony forming unit-fibroblast). Moreover, we found an altered phenotype and reduced replating efficiency upon passaging of BMSC from MDS and AML samples. Expression analysis of genes involved in adipo- and osteogenic differentiation as well as Wnt- and Notch-signalling pathways showed significantly reduced levels of DLK1, an early adipogenic cell fate inhibitor in MDS and AML BMSC. Matching this observation, functional analysis showed significantly increased in vitro adipogenic differentiation potential in BMSC from MDS and AML patients. Overall, our data show BMSC with a reduced CFU-F capacity, and an altered molecular and functional profile from MDS and AML patients in culture, indicating an increased adipogenic lineage potential that is likely to provide a disease-promoting microenvironment.


2015 ◽  
Vol 24 (23) ◽  
pp. 2822-2840 ◽  
Author(s):  
Lindolfo da Silva Meirelles ◽  
Tathiane Maistro Malta ◽  
Virgínia Mara de Deus Wagatsuma ◽  
Patrícia Viana Bonini Palma ◽  
Amélia Goes Araújo ◽  
...  

2011 ◽  
Vol 39 (5) ◽  
pp. 546-557.e8 ◽  
Author(s):  
Caroline Bret ◽  
Dirk Hose ◽  
Thierry Reme ◽  
Alboukadel Kassambara ◽  
Anja Seckinger ◽  
...  

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