scholarly journals The Cross-Talk between Myeloid and Mesenchymal Stem Cells of Human Bone Marrow Represents a Biomarker of Aging That Regulates Immune Response and Bone Reabsorption

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 1
Author(s):  
Maria Elisa Perico ◽  
Tommaso Maluta ◽  
Giamaica Conti ◽  
Antonio Vella ◽  
Lisa Provezza ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Elderly People ◽  
Suppressor Cells ◽  
Cell Types ◽  
Mesenchymal Cells ◽  
Cell Contact ◽  
Biomarkers Of Aging

One of the mechanisms that characterizes the aging process of different organs is the accumulation of fat. Different authors have demonstrated that adipose tissue replaces the loss of other cell types, deriving from mesenchymal cells. During aging, there is substitution or trans-differentiation of mesenchymal cells with other cells having the same embryological origin. Newly formed adipocytes were also observed in the trabecular matrix of elderly people’s bones, associated with myeloid cells. In this study, we have investigated the relationship between immature myeloid-derived suppressor cells (I-MDSCs) and mesenchymal stem cells (MSCs) in bone marrow (BM) samples harvested from 57 patients subjected to different orthopedic surgeries. Patients aged from 18 to 92 years were considered in order to compare the cellular composition of bone marrow of young and elderly people, considered a biomarker of immunity, inflammation, and bone preservation. The I-MDSC percentage was stable during aging, but in elderly people, it was possible to observe a strong basal immunosuppression of autologous and heterologous T cells’ proliferation. We hypothesized that this pattern observed in elders depends on the progressive accumulation in the BM of activating stimuli, including cell–cell contact, or the production of different cytokines and proteins that induce the differentiation of bone marrow mesenchymal stem cells in adipocytes. The collected data provided underline the importance of specific biomarkers of aging that promote a reduction in immune response and incremented inflammatory pathways, leading to bone reabsorption in elderly people.

scholarly journals Comparison of the Proliferation and Differentiation Potential of Human Urine-, Placenta Decidua Basalis-, and Bone Marrow-Derived Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Chengguang Wu ◽  
Long Chen ◽  
Yi-zhou Huang ◽  
Yongcan Huang ◽  
Ornella Parolini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Differentiation ◽  
Cell Types ◽  
Stem Cell Marker ◽  
Differentiation Potential ◽  
Multipotent Stem Cells ◽  
Decidua Basalis

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.

scholarly journals Comparison of the Biological Characteristics of Mesenchymal Stem Cells Derived from Bone Marrow and Skin

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Ruifeng Liu ◽  
Wenjuan Chang ◽  
Hong Wei ◽  
Kaiming Zhang
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
Culture Conditions ◽  
Biological Characteristics ◽  
Cytokine Secretion ◽  
Surface Markers ◽  
Tissue Repair And Regeneration

Mesenchymal stem cells (MSCs) exhibit high proliferation and self-renewal capabilities and are critical for tissue repair and regeneration during ontogenesis. They also play a role in immunomodulation. MSCs can be isolated from a variety of tissues and have many potential applications in the clinical setting. However, MSCs of different origins may possess different biological characteristics. In this study, we performed a comprehensive comparison of MSCs isolated from bone marrow and skin (BMMSCs and SMSCs, resp.), including analysis of the skin sampling area, separation method, culture conditions, primary and passage culture times, cell surface markers, multipotency, cytokine secretion, gene expression, and fibroblast-like features. The results showed that the MSCs from both sources had similar cell morphologies, surface markers, and differentiation capacities. However, the two cell types exhibited major differences in growth characteristics; the primary culture time of BMMSCs was significantly shorter than that of SMSCs, whereas the growth rate of BMMSCs was lower than that of SMSCs after passaging. Moreover, differences in gene expression and cytokine secretion profiles were observed. For example, secretion of proliferative cytokines was significantly higher for SMSCs than for BMMSCs. Our findings provide insights into the different biological functions of both cell types.

280 MULTILINEAGE POTENTIAL OF PORCINE BONE MARROW AND ADIPOSE-DERIVED MESENCHYMAL STEM CELLS IN 3-D ALGINATE HYDROGELS

2009 ◽  
Vol 21 (1) ◽  
pp. 237 ◽  
Author(s):  
D. Kim ◽  
A. J. Maki ◽  
H.-J. Kong ◽  
E. Monaco ◽  
M. Bionaz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Cell Types ◽  
Scaffold Material ◽  
Over Time

Adipose tissue presents an appealing alternative to bone marrow as a source of mesenchymal stem cells (MSC). However, in order to enhance cell proliferation and differentiation, 3-dimensional (3-D) culture may be required. A 3-D culture has benefits due to its more in vivo-like environment. Further, to form a functional tissue, a scaffold material is required to ensure proper shape and allow for efficient delivery of nutrients and growth factors. Alginate, a resorbable hydrogel, is a potential injectable scaffold for fat and bone tissue engineering due to its high biocompatibility, gelation with calcium and slow dissolution in a physiologic environment. In the present study, we examined the viability, gene expression and morphology of MSC, isolated from porcine adipose (ADSC) and bone marrow (BMSC), during osteogenic and adipogenic differentiation in a 3D alginate hydrogel environment for 0, 7 and 14 days (d). ADSC and BMSC were infused into alginate hydrogels, which polymerized upon the addition of Ca+2 ions. Both stem cell types were differentiated into osteoblasts using 0.1 μm dexamethasone, 10 mm beta glycerophosphate and 50 μm ascorbic acid, whereas adipocytes were differentiated using 10 μm insulin, 1 μm dexamethasone, and 0.5 mm IBMX. Osteogenic differentiation was confirmed using alkaline phosphatase, Von Kossa, and alizarin red S staining and adipogenic differentiation was confirmed using Oil Red O. Cell viability and proliferation was quantified using the MTT assay. Gene expression was measured using qPCR. The morphology of ADSC and BMSC differentiated toward osteogenic lineages changed with both cell types forming osteogenic nodules over time. The nodules formed by ADSC were larger in diameter than those formed by BMSC. Unlike the osteogenic cells that formed nodules, the ADSC and BMSC differentiated into adipogenic cells showed no significant changes in cell size or aggregation. Gene expression results indicated increased PPARG expression in BMSC with time whereas ADSC showed a peak of expression on day 7 and then decreased. ADSC showed increased (14-fold) PPRG expression when compared with BMSC. ADSC had 160-fold less expression of ALP than BMSC. BMSC showed a 16-fold higher expression level of BGLAP than ADSC. ADSC showed a 15.8% higher expression than BMSC for COL1a1. Both ADSC and BMSC showed similar trends SPARC expression, but BMSC had a 12-fold higher expression of SPP1 than ADSC. In summary, both types of mesenchymal stem cells successfully differentiated into both lineages and maintained viability in the hydrogel over time. In conclusion, alginate is a viable scaffold material for the differentiation of mesenchymal stem cells for tissue engineering applications. These results allow for future studies using the pig as an in vivo fat and bone tissue engineering model. This research was supported by the Illinois Regenerative Medicine Institute.

scholarly journals Dose-Response Tendon-Specific Markers Induction by Growth Differentiation Factor-5 in Human Bone Marrow and Umbilical Cord Mesenchymal Stem Cells

2020 ◽  
Vol 21 (16) ◽  
pp. 5905
Author(s):  
Maria Camilla Ciardulli ◽  
Luigi Marino ◽  
Erwin Pavel Lamparelli ◽  
Maurizio Guida ◽  
Nicholas Robert Forsyth ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Differentiation Factor ◽  
Anti Inflammatory ◽  
Growth Differentiation Factor 5

Mesenchymal stem cells derived from human bone marrow (hBM-MSCs) are utilized in tendon tissue-engineering protocols while extra-embryonic cord-derived, including from Wharton’s Jelly (hWJ-MSCs), are emerging as useful alternatives. To explore the tenogenic responsiveness of hBM-MSCs and hWJ-MSCs to human Growth Differentiation Factor 5 (hGDF-5) we supplemented each at doses of 1, 10, and 100 ng/mL of hGDF-5 and determined proliferation, morphology and time-dependent expression of tenogenic markers. We evaluated the expression of collagen types 1 (COL1A1) and 3 (COL3A1), Decorin (DCN), Scleraxis-A (SCX-A), Tenascin-C (TNC) and Tenomodulin (TNMD) noting the earliest and largest increase with 100 ng/mL. With 100 ng/mL, hBM-MSCs showed up-regulation of SCX-A (1.7-fold) at Day 1, TNC (1.3-fold) and TNMD (12-fold) at Day 8. hWJ-MSCs, at the same dose, showed up-regulation of COL1A1 (3-fold), DCN (2.7-fold), SCX-A (3.8-fold) and TNC (2.3-fold) after three days of culture. hWJ-MSCs also showed larger proliferation rate and marked aggregation into a tubular-shaped system at Day 7 (with 100 ng/mL of hGDF-5). Simultaneous to this, we explored the expression of pro-inflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokines across for both cell types. hBM-MSCs exhibited a better balance of pro-inflammatory and anti-inflammatory cytokines up-regulating IL-1β (11-fold) and IL-10 (10-fold) at Day 8; hWJ-MSCs, had a slight expression of IL-12A (1.5-fold), but a greater up-regulation of IL-10 (2.5-fold). Type 1 collagen and tenomodulin proteins, detected by immunofluorescence, confirming the greater protein expression when 100 ng/mL were supplemented. In the same conditions, both cell types showed specific alignment and shape modification with a length/width ratio increase, suggesting their response in activating tenogenic commitment events, and they both potential use in 3D in vitro tissue-engineering protocols.

scholarly journals The impact of cryopreservation on bone marrow-derived mesenchymal stem cells: a systematic review

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Soukaina Bahsoun ◽  
Karen Coopman ◽  
Elizabeth C. Akam
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Types ◽  
Surface Marker Expression ◽  
Wide Range ◽  
And Migration ◽  
The Impact

AbstractMesenchymal stem cells (MSCs) represent an invaluable asset for the field of cell therapy. Human Bone marrow-derived MSCs (hBM-MSCs) are one of the most commonly used cell types in clinical trials. They are currently being studied and tested for the treatment of a wide range of diseases and conditions. The future availability of MSCs therapies to the public will require a robust and reliable delivery process. Cryopreservation represents the gold standard in cell storage and transportation, but its effect on BM-MSCs is still not well established. A systematic review was conducted to evaluate the impact of cryopreservation on BM-MSCs and to attempt to uncover the reasons behind some of the controversial results reported in the literature. Forty-one in vitro studies were analysed, and their results organised according to the cell attributes they assess. It was concluded that cryopreservation does not affect BM-MSCs morphology, surface marker expression, differentiation or proliferation potential. However, mixed results exist regarding the effect on colony forming ability and the effects on viability, attachment and migration, genomic stability and paracrine function are undefined mainly due to the huge variabilities governing the cryopreservation process as a whole and to the lack of standardised assays.

SDF-1-CXCR4 and HGF-c-met Axes Regulate Mobilization/Recruitment to Injured Tissue of Human Mesenchymal Stem Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2331-2331 ◽  
Author(s):  
Bo-Ra Son ◽  
Dongling Zhao ◽  
Leah A. Marquez-Curtis ◽  
Neeta Shirvaikar ◽  
Mariusz Z. Ratajczak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Therapeutic Tool ◽  
Chemotaxis Assay ◽  
Injured Tissue ◽  
Organ Tissue ◽  
Hepatocyte Growth

Abstract Human mesenchymal stem cells (MSC) have been shown to egress from the bone marrow (BM), circulate in peripheral blood (PB) and differentiate into many cell types, making them attractive as a potential therapeutic tool for organ/tissue regeneration. However the signals required for their mobilization into PB and their recruitment into injured sites are not fully understood. We previously reported that stromal-derived factor (SDF)-1 and hepatocyte growth factor (HGF) are upregulated at sites of tissue damage (Cancer Research2003; 63:7926; Leukemia2004; 18:29) and in this study we examined whether these factors mediate the migration of MSC. We investigated (i) the expression in MSC of CXCR4 and c-met, the cognate receptors of SDF-1 and HGF, (ii) whether they are functional after early and late passages (using a chemotaxis assay across fibronectin and the reconstituted basement membrane Matrigel), and (iii) whether MSC express matrix metalloproteinases (MMPs) known to facilitate mobilization and homing of stem cells. MSC were derived from human bone marrow (BM) or cord blood (CB) and maintained for up to 18 passages (in IMDM and 10–20% FCS) with monitoring of markers for cardiac (Nkx2.5/Csx, GATA-4 and MEF2-C), skeletal muscle (Myo-D and myogenin) and endothelial cells (VE-cadherin and VEGFR-2). We found that (i) CB and BM MSC strongly express CXCR4 and c-met transcripts for up to 15 passages, (ii) these receptors are functional as the MSC cells were chemotactic and chemoinvasive (across Matrigel) towards gradients of SDF-1 (100 ng/mL) or HGF (40 ng/mL), and (iii) CB and BM MSC express MMP-2 mRNA and secrete both latent and active forms of MMP-2. Moreover, we found that CB and BM MSC expressed mRNA for all three cardiac markers and the endothelial marker VE-cadherin, indicating their potential for heart regeneration. In conclusion, these results indicate that the SDF-1-CXCR4 and HGF-c-met axes are important signaling pathways in MSC mobilization and their trafficking in PB, and could be involved in recruitment of MSC to damaged tissues (e.g., myocardium).

Notch Signaling Pathway in Hematopoietic Stem Cells Is Activated through Interactive Communication with Mesenchymal Stem Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1408-1408
Author(s):  
Yuji Kikuchi ◽  
Akihiro Kume ◽  
Masashi Urabe ◽  
Hiroaki Mizukami ◽  
Takahiro Suzuki ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Notch Signaling ◽  
Notch Signaling Pathway ◽  
Cell Contact ◽  
Rt Pcr ◽  
Interactive Communication ◽  
Hematopoietic Stem ◽  
Notch Ligands

Abstract Mesenchymal stem cells (MSCs), which are key elements of hematopoietic microenvironment in bone marrow, are known to play a critical role in supporting hematopoiesis. A variety of hematopoietic growth factors are produced from MSCs, and cell-to-cell contact is also believed to be crucial in the interaction between hematopoietic stem cells (HSCs) and MSCs. However, the molecular mechanisms of hematopoiesis-supporting ability of MSCs are still unclear. In particular, there is little information regarding the effects of HSCs on MSC function. In the present study, we investigated the cellular and molecular events in the interactive communication between HSCs and MSCs using a differentiation-inducible MSC model; i.e. parent C3H10T1/2 cells and 10T1/2-derived cell lines, A54 preadipocytes and M1601 myoblasts. These cells were co-cultured with murine HSCs (Lin-Sca1+) isolated from bone marrow. There was 9-fold increase in the number of hematopoietic progenitors after co-culture with A54 preadipocytes, whereas there was no increase when co-cultured with parent 10T1/2 or M1601 cells. More intriguingly, cobblestone areas were observed only when HSCs were co-cultured with A54 cells. Quantitative RT-PCR showed that A54 cells express significantly higher levels of SCF, SDF-1, and angiopoietin-1 (Ang-1) compared with parent 10T1/2 cells and M1601 cells, although these cytokines were not up-regulated when co-cultured with HSCs. To search for the genes involved in the interaction between HSCs and MSCs, we compared gene expression profiles before and after the co-culture by using a microarray analysis. Among the candidate genes with up-regulation after the co-culture, we paid attention to the Notch system, because Notch ligands are considered to play an important role in nurturing HSCs within the hematopoietic microenvironment. As a result, the expression of Notch ligands, Jagged1 and Dll3, increased in A54 cells after the coculture with HSCs. On the other hand, the expression of Notch1 and Hes-1 also increased in HSCs upon co-culture with A54 cells. These data were confirmed by quantitative RT-PCR. Moreover, when HSCs were co-cultured with A54 cells without cell-to-cell contact using Transwell permeable supports, there was neither increase in the number of progenitors in the upper wells, nor the up-regulation of Notch ligands in A54 cells in the lower wells. These findings support the idea that HSCs act on MSCs to induce the expression of Notch ligands via direct cell-to-cell contact and that the Notch ligands derived from MSCs act on HSCs in turn to activate Notch signaling pathway, possibly leading to the cobblestone formation with the maintenance of immature state of HSCs. The Notch system may be one of the critical elements in the interactive communication between HSCs and MSCs.

scholarly journals The Antihypertensive Drug Nifedipine Modulates the Metabolism of Chondrocytes and Human Bone Marrow-Derived Mesenchymal Stem Cells

2019 ◽  
Author(s):  
Ilona Uzieliene ◽  
Eiva Bernotiene ◽  
Greta Urbonaite ◽  
Jaroslav Denkovskij ◽  
Edvardas Bagdonas ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Antihypertensive Drug ◽  
Mitochondrial Respiration ◽  
Collagen Type ◽  
Cell Types ◽  
Cartilage Tissue ◽  
Type Ii ◽  
Collagen Type Ii

Abstract Aging is associated with the development of various chronic diseases, in which both hypertension and osteoarthritis (OA) are dominant. Currently, there is no effective treatment for OA, whereas hypertension is often treated using L-type voltage-operated calcium channel (VOCC) blocking drugs, nifedipine being among the most classical ones. Although nifedipine together with other VOCC inhibitors plays an important role in people wellbeing, there are unresolved questions on its possible effect on cartilage tissue homeostasis and the development of OA. Due to that, the aim of this study was to analyse the effects of nifedipine on metabolic processes in human chondrocytes and bone marrow mesenchymal stem cells (BMMSCs). To analyze whether those events were mediated specifically through VOCC, agonist BayK8644 was used. Our results demonstrate that nifedipine downregulated chondrocyte proliferation rate as well as mitochondrial respiration and ATP production (Agilent Seahorse) in both cell types. Analysis of cartilage explant histological sections by electron microscopy also suggested that part of mitochondria lose their activity in response to nifedipine.However, switch of energetic metabolic pathway towards glycolytic was observed only in chondrocytes. Stimulation with either nifedipine or BayK8644 resulted in elevated production of collagen type II and proteoglycans in micromass cultures under chondrogenic condition, although the effects of VOCC inhibitor Bay8466 were less expressed. Nitric oxide (NO) activity, as measured by flow cytometry, was upregulated by nifedipine in BMMSCs and particularly chondrocytes, suggesting that NO at least in part may account for the effects of nifedipine on metabolism in both tested cell types.Taken together, we conclude that antihypertensive drug nifedipine inhibits mitochondrial respiration in both chondrocytes and BMMSCs and that these effects may be associated with increased NO accumulation and pro-inflammatory activity. Glycolytic capacity was enhanced only in chondrocytes, suggesting that these cells have the capacity to switch from oxidative phosphorylation to glycolysis and alter their metabolic activity in response to VOCC inhibition. Finally, nifedipine stimulated production of collagen type II and proteoglycans in both cell types, implying its potentially beneficial anabolic effects on articular cartilage. These results highlight a potential link between consumption of antihypertensive drugs and cartilage health

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