scholarly journals LRP5-Mediated Lipid Uptake Modulates Osteogenic Differentiation of Bone Marrow Mesenchymal Stromal Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiachen Lin ◽  
Zhifa Zheng ◽  
Jieying Liu ◽  
Guihua Yang ◽  
Ling Leng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Target Genes ◽  
Density Lipoprotein ◽  
Conditional Knockout ◽  
Beta Catenin ◽  
Lipid Uptake

Nutritional microenvironment determines the specification of progenitor cells, and lipid availability was found to modulate osteogenesis in skeletal progenitors. Here, we investigated the implications of lipid scarcity in the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) and the role of low-density lipoprotein receptor-related protein 5 (LRP5), a co-receptor transducing canonical Wnt/beta-catenin signals, in BMSC lipid uptake during osteogenesis. The osteogenic differentiation of murine BMSCs was suppressed by lipid scarcity and partially rescued by additional fatty acid treatment with oleate. The enhancement of osteogenesis by oleate was found to be dosage-dependent, along with the enhanced activation of beta-catenin and Wnt target genes. Conditional knockout (CKO) of Lrp5 gene in murine mesenchymal lineage using Lrp5fl/fl;Prrx1-cre mice led to decreased bone quality and altered fat distribution in vivo. After Lrp5 ablation using adenoviral Cre-recombinase, the accumulation of lipid droplets in BMSC cytoplasm was significantly reduced, and the osteogenesis of BMSCs was suppressed. Moreover, the impaired osteogenesis due to either lipid scarcity or Lrp5 ablation could be rescued by recombinant Wnt3a protein, indicating that the osteogenesis induced by Wnt/beta-catenin signaling was independent of LRP5-mediated lipid uptake. In conclusion, lipid scarcity suppresses BMSC osteogenic differentiation. LRP5 plays a role in the uptake of lipids in BMSCs and therefore mediates osteogenic specification.

scholarly journals Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo

Materials ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 208
Author(s):  
Hai Thanh Pham ◽  
Mitsuaki Ono ◽  
Emilio Satoshi Hara ◽  
Ha Thi Thu Nguyen ◽  
Anh Tuan Dang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Bone Marrow ◽  
Stem Cell ◽  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Bone Healing ◽  
Stromal Cells ◽  
Mrna Levels

Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss.

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

Cells ◽  
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.

scholarly journals Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo

2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Lynn M Pezzanite ◽  
Lisa A Fortier ◽  
Douglas F Antczak ◽  
Jennifer M Cassano ◽  
Margaret M Brosnahan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Allogeneic Bone Marrow ◽  
Antibody Responses ◽  
Allogeneic Bone

In vivo systemic delivery of bone marrow-derived mesenchymal stromal cells results in enhanced fascial wound healing

2006 ◽  
Vol 203 (3) ◽  
pp. S42
Author(s):  
David S. Kwon ◽  
Tina Gao ◽  
Bo Liu ◽  
Deborah Dulchavsky ◽  
Scott Dulchavsky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Systemic Delivery

In Vivo Effects of Human Bone Marrow Mesenchymal Stromal Cells on the Development of Experimental B16 Melanoma in Mice

2020 ◽  
Vol 168 (4) ◽  
pp. 561-565 ◽  
Author(s):  
V. N. Petrov ◽  
E. V. Isaeva ◽  
S. E. Ulyanenko ◽  
E. E. Beketov ◽  
E. M. Yatsenko ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
B16 Melanoma ◽  
Human Bone ◽  
Human Bone Marrow ◽  
In Vivo Effects

scholarly journals MRI Tracking of SPIO- and Fth1-Labeled Bone Marrow Mesenchymal Stromal Cell Transplantation for Treatment of Stroke

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaolei Huang ◽  
Yang Xue ◽  
Jinliang Wu ◽  
Qing Zhan ◽  
Jiangmin Zhao
Keyword(s):  
Bone Marrow ◽  
Prussian Blue ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Signal Intensity ◽  
Immunofluorescent Staining ◽  
Blue Staining

We aimed to identify a suitable method for long-term monitoring of the migration and proliferation of mesenchymal stromal cells in stroke models of rats using ferritin transgene expression by magnetic resonance imaging (MRI). Bone marrow mesenchymal stromal cells (BMSCs) were transduced with a lentivirus containing a shuttle plasmid (pCDH-CMV-MCS-EF1-copGFP) carrying the ferritin heavy chain 1 (Fth1) gene. Ferritin expression in stromal cells was evaluated with western blotting and immunofluorescent staining. The iron uptake of Fth1-BMSCs was measured with Prussian blue staining. Following surgical introduction of middle cerebral artery occlusion, Fth1-BMSCs and superparamagnetic iron oxide- (SPIO-) labeled BMSCs were injected through the internal jugular vein. The imaging and signal intensities were monitored by diffusion-weighted imaging (DWI), T2-weighted imaging (T2WI), and susceptibility-weighted imaging (SWI) in vitro and in vivo. Pathology was performed for comparison. We observed that the MRI signal intensity of SPIO-BMSCs gradually reduced over time. Fth1-BMSCs showed the same signal intensity between 10 and 60 days. SWI showed hypointense lesions in the SPIO-BMSC (traceable for 30 d) and Fth1-BMSC groups. T2WI was not sensitive enough to trace Fth1-BMSCs. After transplantation, Prussian blue-stained cells were observed around the infarction area and in the infarction center in both transplantation models. Fth1-BMSCs transplanted for treating focal cerebral infarction were safe, reliable, and traceable by MRI. Fth1 labeling was more stable and suitable than SPIO labeling for long-term tracking. SWI was more sensitive than T2W1 and suitable as the optimal MRI-tracking sequence.

Mouse adipose-derived mesenchymal stromal cells undergo osteogenic differentiation in vitro and in vivo

2004 ◽  
Vol 199 (3) ◽  
pp. 62
Author(s):  
Yun-Ying Shi ◽  
Randall Nacamuli ◽  
Ali Salim ◽  
Oliver Aalami ◽  
Catherine Cowan ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells

scholarly journals The Role of Prep1 in the Regulation of Mesenchymal Stromal Cells

2019 ◽  
Vol 20 (15) ◽  
pp. 3639 ◽  
Author(s):  
Giorgia Maroni ◽  
Daniele Panetta ◽  
Raffaele Luongo ◽  
Indira Krishnan ◽  
Federica La Rosa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cell Fate ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Gene Dosage ◽  
Homeobox Gene ◽  
Fate Decision

Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene Prep1 as a candidate regulatory molecule, by adopting Prep1 hypomorphic mice as a model to investigate the effects of Prep1 downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of Prep1 are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased Prep1 gene dosage favors a pro-adipogenic phenotype and induces a “browning” effect in all fat tissues.

Lenalidomide Modulates the Phenotype and Function of Human Mesenchymal Stromal Cells From Healthy Donors and MDS Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3816-3816
Author(s):  
Manja Wobus ◽  
Gwendolin Dünnebier ◽  
Silvia Feldmann ◽  
Gerhard Ehninger ◽  
Martin Bornhauser ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Osteogenic Differentiation ◽  
Clinical Efficacy ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Morphological Changes ◽  
Adipogenic Differentiation ◽  
Healthy Controls ◽  
Healthy Donors

Abstract Abstract 3816 Poster Board III-752 Introduction Recent studies in patients with MDS have clearly demonstrated the clinical efficacy of lenalidomide. However, its exact mechanisms of action have not been elucidated yet. Myelosuppression is the most common adverse event and seems to be dependent on dose as well MDS subtype, being rather infrequent in patients other than del5q. The aim of this study was to investigate whether lenalidomide affects the bone marrow microenvironment. Therefore, we analyzed in-vitro characteristics of isolated mesenchymal stromal cells (MSCs) from MDS patients and from healthy controls. Methods Bone marrow samples were collected from healthy donors (n=5) and patients with MDS (del5q MDS n=3, RA n=2, RAEB1/2 n=3). MSCs were isolated according to the standard adhesion protocol and cultured in the presence or absence of lenalidomide. Results Lenalidomide treatment of MSCs caused no morphological changes but proliferation was slightly increased. Typical surface molecules as CD73, CD90, CD105 and CD166 were expressed in MSCs from MDS patients at comparable levels to healthy controls. Lenalidomide treatment caused an upregulation of CD29 by 17.8 ± 4.4% and of CD73 by 24 ± 5.7% (mean fluorescence intensity). Investigating the cytokine production, we found lower IL-8 mRNA and protein levels in MSCs from MDS patients (mean in MDS MSC: 138.1 pg/ml vs. mean in healthy MSC: 1177 pg/ml). Interestingly, the IL-8 production can be increased by approximately 40% under lenalidomide treatment. MDS MSCs retained the capacity for adipogenic and osteogenic differentiation as well as their supportive function towards hematopoietic cells in long term culture-initiating assays (LTC-IC). However, the LTC-IC frequency was lower on MSC which had been preincubated with lenalidomide compared to controls. Lenalidomide also slightly accelerated osteogenic differentiation because mineralization started as early as on day 5 with lenalidomide whereas in the control cells first calcium deposits were visible after 7 days. Other samples showed augmented lipid vacuoles after adipogenic differentiation under lenalidomide treatment. Conclusion In conclusion, lenalidomide modulates the phenotype of MSC and leads to an increase of their IL-8 secretion by a yet unknown mechanism. Whether these in-vitro effects are associated with the clinical efficacy of this compound in patients with MDS remains to be investigated. Disclosures: Platzbecker: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Sign in / Sign up

Export Citation Format

Share Document