Mesenchymal Stem/Stromal Cells from Discarded Neonatal Sternal Tissue: In Vitro Characterization and Angiogenic Properties

Autologous and nonautologous bone marrow mesenchymal stem/stromal cells (MSCs) are being evaluated as proangiogenic agents for ischemic and vascular disease in adults but not in children. A significant number of newborns and infants with critical congenital heart disease who undergo cardiac surgery already have or are at risk of developing conditions related to inadequate tissue perfusion. During neonatal cardiac surgery, a small amount of sternal tissue is usually discarded. Here we demonstrate that MSCs can be isolated from human neonatal sternal tissue using a nonenzymatic explant culture method. Neonatal sternal bone MSCs (sbMSCs) were clonogenic, had a surface marker expression profile that was characteristic of bone marrow MSCs, were multipotent, and expressed pluripotency-related genes at low levels. Neonatal sbMSCs also demonstrated in vitro proangiogenic properties. Sternal bone MSCs cooperated with human umbilical vein endothelial cells (HUVECs) to form 3D networks and tubes in vitro. Conditioned media from sbMSCs cultured in hypoxia also promoted HUVEC survival and migration. Given the neonatal source, ease of isolation, and proangiogenic properties, sbMSCs may have relevance to therapeutic applications.

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RETRACTED ARTICLE: Effect of the co-culture of human bone marrow mesenchymal stromal cells with human umbilical vein endothelial cells in vitro

Journal of Receptors and Signal Transduction ◽

10.3109/10799893.2015.1075043 ◽

2015 ◽

Vol 36 (3) ◽

pp. 221-224 ◽

Cited By ~ 2

Author(s):

Qiwang Lin ◽

Linhui Wang ◽

Yuling Bai ◽

Menglin Hu ◽

Jianling Mo ◽

...

Keyword(s):

Bone Marrow ◽

Endothelial Cells ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Umbilical Vein ◽

Human Bone ◽

Human Umbilical Vein ◽

Retracted Article ◽

Umbilical Vein Endothelial Cells

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Growth characteristics of human bone marrow mesenchymal stromal cells at cultivation on synthetic polyelectrolyte nanofilms in vitro

Heliyon ◽

10.1016/j.heliyon.2021.e06517 ◽

2021 ◽

Vol 7 (3) ◽

pp. e06517

Author(s):

Lyudmila M. Mezhevikina ◽

Dmitriy A. Reshetnikov ◽

Maria G. Fomkina ◽

Nurbol O. Appazov ◽

Saltanat Zh. Ibadullayeva ◽

...

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Growth Characteristics ◽

Human Bone ◽

Human Bone Marrow

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Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells

Cells ◽

10.3390/cells10020268 ◽

2021 ◽

Vol 10 (2) ◽

pp. 268

Author(s):

Jonathan Ribot ◽

Cyprien Denoeud ◽

Guilhem Frescaline ◽

Rebecca Landon ◽

Hervé Petite ◽

...

Keyword(s):

Type 2 Diabetes ◽

Bone Marrow ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Therapeutic Modality ◽

Multipotent Stromal Cells ◽

Cell Therapies

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine. BMMSCs were obtained from Zucker diabetic fatty (ZDF; an obese-T2DM model) rats and their lean littermates (ZL; controls), and cultured under normoglycemic conditions. The BMMSCs derived from ZDF animals were fewer in number, with limited clonogenicity (by 2-fold), adhesion (by 2.9-fold), proliferation (by 50%), migration capability (by 25%), and increased apoptosis rate (by 2.5-fold) compared to their ZL counterparts. Compared to the cultured ZL-BMMSCs, the ZDF-BMMSCs exhibited (i) enhanced adipogenic differentiation (increased number of lipid droplets by 2-fold; upregulation of the Pparg, AdipoQ, and Fabp genes), possibly due to having been primed to undergo such differentiation in vivo prior to cell isolation, and (ii) different angiogenesis-related gene expression in vitro and decreased proangiogenic potential after transplantation in nude mice. These results provided evidence that the T2DM environment impairs BMMSC expansion and select functions pertinent to their efficacy when used in autologous cell therapies.

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Bone marrow stromal cells from MDS and AML patients show increased adipogenic potential with reduced Delta-like-1 expression

Scientific Reports ◽

10.1038/s41598-021-85122-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Marie-Theresa Weickert ◽

Judith S. Hecker ◽

Michèle C. Buck ◽

Christina Schreck ◽

Jennifer Rivière ◽

...

Keyword(s):

Bone Marrow ◽

Cell Fate ◽

Stromal Cells ◽

Adipogenic Differentiation ◽

Cell Types ◽

Bone Marrow Niche ◽

Differentiation Potential ◽

Hematopoietic Stem ◽

Bm Niche

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.

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Atelocollagen Sponge as a Stem Cell Implantation Scaffold for the Treatment of Scarred Vocal Folds

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348941011901110 ◽

2010 ◽

Vol 119 (11) ◽

pp. 805-810 ◽

Cited By ~ 1

Author(s):

Satoshi Ohno ◽

Shigeru Hirano ◽

Ichiro Tateya ◽

Shin-Ichi Kanemaru ◽

Hiroo Umeda ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stromal Cells ◽

Fluorescent Protein ◽

In Vitro Study ◽

Vocal Folds ◽

Green Fluorescent ◽

Cell Implantation

Objectives: Treatment of vocal fold scarring remains a therapeutic challenge. Our group previously reported the efficacy of treating injured vocal folds by implantation of bone marrow—derived stromal cells containing mesenchymal stem cells. Appropriate scaffolding is necessary for the stem cell implant to achieve optimal results. Terudermis is an atelocollagen sponge derived from calf dermis. It has large pores that permit cellular entry and is degraded in vivo. These characteristics suggest that this material may be a good candidate for use as scaffolding for implantation of cells. The present in vitro study investigated the feasibility of using Terudermis as such a scaffold. Methods: Bone marrow—derived stromal cells were obtained from GFP (green fluorescent protein) mouse femurs. The cells were seeded into Terudermis and incubated for 5 days. Their survival, proliferation, and expression of extracellular matrix were examined. Results: Bone marrow—derived stromal cells adhered to Terudermis and underwent significant proliferation. Immunohistochemical examination demonstrated that adherent cells were positive for expression of vimentin, desmin, fibronectin, and fsp1 and negative for beta III tubulin. These findings indicate that these cells were mesodermal cells and attached to the atelocollagen fibers biologically. Conclusions: The data suggest that Terudermis may have potential as stem cell implantation scaffolding for the treatment of scarred vocal folds.

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Evaluation of Browning Agents on the White Adipogenesis of Bone Marrow Mesenchymal Stromal Cells: A Contribution to Fighting Obesity

Cells ◽

10.3390/cells10020403 ◽

2021 ◽

Vol 10 (2) ◽

pp. 403

Author(s):

Girolamo Di Maio ◽

Nicola Alessio ◽

Ibrahim Halil Demirsoy ◽

Gianfranco Peluso ◽

Silverio Perrotta ◽

...

Keyword(s):

Bone Marrow ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

White Adipocyte ◽

Drug Candidates ◽

Fat Depots ◽

Treatment Of Obesity ◽

White Fat

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

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The lower in vitro chondrogenic potential of canine adipose tissue-derived mesenchymal stromal cells (MSC) compared to bone marrow derived MSC is not improved by BMP-2 or BMP-6

The Veterinary Journal ◽

10.1016/j.tvjl.2020.105605 ◽

2020 ◽

pp. 105605

Author(s):

M. Teunissen ◽

F. Verseijden ◽

F.M. Riemers ◽

G.J.V.M. van Osch ◽

M.A. Tryfonidou

Keyword(s):

Bone Marrow ◽

Adipose Tissue ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Chondrogenic Potential

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A Method for Measurement of Drug Sensitivity of Myeloma Cells Co-Cultured with Bone Marrow Stromal Cells

CrossRef Listing of Deleted DOIs ◽

10.1177/1087057113478168 ◽

2013 ◽

Vol 18 (6) ◽

pp. 637-646 ◽

Cited By ~ 18

Author(s):

Kristine Misund ◽

Katarzyna A. Baranowska ◽

Toril Holien ◽

Christoph Rampa ◽

Dionne C. G. Klein ◽

...

Keyword(s):

Bone Marrow ◽

Cell Survival ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Large Scale ◽

Stromal Cell ◽

Marrow Stromal Cells ◽

Cell Nuclei ◽

Myeloma Cells

The tumor microenvironment can profoundly affect tumor cell survival as well as alter antitumor drug activity. However, conventional anticancer drug screening typically is performed in the absence of stromal cells. Here, we analyzed survival of myeloma cells co-cultured with bone marrow stromal cells (BMSC) using an automated fluorescence microscope platform, ScanR. By staining the cell nuclei with DRAQ5, we could distinguish between BMSC and myeloma cells, based on their staining intensity and nuclear shape. Using the apoptotic marker YO-PRO-1, the effects of drug treatment on the viability of the myeloma cells in the presence of stromal cells could be measured. The method does not require cell staining before incubation with drugs, and less than 5000 cells are required per condition. The method can be used for large-scale screening of anticancer drugs on primary myeloma cells. This study shows the importance of stromal cell support for primary myeloma cell survival in vitro, as half of the cell samples had a marked increase in their viability when cultured in the presence of BMSC. Stromal cell–induced protection against common myeloma drugs is also observed with this method.

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