Influence of in vitro biomimicked stem cell ‘niche’ for regulation of proliferation and differentiation of human bone marrow-derived mesenchymal stem cells to myocardial phenotypes: serum starvation without aid of chemical agents and prevention of spontan

2013 ◽  
Vol 10 (1) ◽  
pp. E1-E13 ◽  
Author(s):  
Jae Hyung Kim ◽  
Sang-Hyun Shin ◽  
Tian Zhu Li ◽  
Hwal Suh
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell Niche ◽  
Serum Starvation ◽  
Chemical Agents ◽  
Proliferation And Differentiation ◽  
Regulation Of Proliferation ◽  
Cell Niche

scholarly journals Levels of matrix metalloproteinase-2 in committed differentiation of bone marrow mesenchymal stem cells induced by kartogenin

2019 ◽  
Vol 47 (7) ◽  
pp. 3261-3270
Author(s):  
Cheng Wang ◽  
Qiaohui Liu ◽  
Xiaoyuan Ma ◽  
Guofeng Dai
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Matrix Metalloproteinase ◽  
Type Ii Collagen ◽  
Matrix Metalloproteinase 2 ◽  
Type Ii ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells

Objective To measure the inductive effect of kartogenin on matrix metalloproteinase-2 levels during the differentiation of human bone marrow mesenchymal stem cells (hMSCs) into chondrocytes in vitro. Methods In vitro cultured bone marrow hMSCs were grown to the logarithmic phase and then divided into three groups: control group (0 µM kartogenin), 1 µM kartogenin group and 10 µM kartogenin group. After 72 h of culture, cell proliferation and differentiation were observed microscopically. Matrix metalloproteinase-2 (MMP-2) in the cell supernatant and type II collagen levels in the cells were detected by enzyme linked immunosorbent assay and immunofluorescence staining, respectively. Results Kartogenin induced the proliferation and differentiation of hMSCs. With the increase of kartogenin concentration, the level of type II collagen was increased, while the level of MMP-2 decreased. Conclusion These findings indicate that kartogenin can induce hMSCs to differentiate into chondrocytes, and with the increase of kartogenin concentration, degeneration of the cartilage extracellular matrix may be inhibited.

scholarly journals In vitro proliferation and differentiation of canine bone marrow derived mesenchymal stem cells over hydroxyl functionalized CNT substrates

2019 ◽  
Vol 24 ◽  
pp. e00387
Author(s):  
A.P. Madhusoodan ◽  
Kinsuk Das ◽  
Bhabesh Mili ◽  
Kuldeep Kumar ◽  
Ajay Kumar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
In Vitro Proliferation ◽  
Proliferation And Differentiation

scholarly journals Human Fetal Bone Marrow-Derived Mesenchymal Stem Cells Promote the Proliferation and Differentiation of Pancreatic Progenitor Cells and the Engraftment Function of Islet-Like Cell Clusters

2019 ◽  
Vol 20 (17) ◽  
pp. 4083
Author(s):  
Xing Yu Li ◽  
Shang Ying Wu ◽  
Po Sing Leung
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
Proliferation And Differentiation ◽  
Differentiation And Proliferation

Pancreatic progenitor cells (PPCs) are the primary source for all pancreatic cells, including beta-cells, and thus the proliferation and differentiation of PPCs into islet-like cell clusters (ICCs) opens an avenue to providing transplantable islets for diabetic patients. Meanwhile, mesenchymal stem cells (MSCs) can enhance the development and function of different cell types of interest, but their role on PPCs remains unknown. We aimed to explore the mechanism-of-action whereby MSCs induce the in vitro and in vivo PPC/ICC development by means of our established co-culture system of human PPCs with human fetal bone marrow-derived MSCs. We examined the effect of MSC-conditioned medium on PPC proliferation and survival. Meanwhile, we studied the effect of MSC co-culture enhanced PPC/ICC function in vitro and in vivo co-/transplantation. Furthermore, we identified IGF1 as a critical factor responsible for the MSC effects on PPC differentiation and proliferation via IGF1-PI3K/Akt and IGF1-MEK/ERK1/2, respectively. In conclusion, our data indicate that MSCs stimulated the differentiation and proliferation of human PPCs via IGF1 signaling, and more importantly, promoted the in vivo engraftment function of ICCs. Taken together, our protocol may provide a mechanism-driven basis for the proliferation and differentiation of PPCs into clinically transplantable islets.

Ectopic Human Mesenchymal Stem Cell-Coated Scaffolds Create An In Vivo Leukemia Niche in NOD/SCID Mice.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 559-559
Author(s):  
Sarah Rivkah Vaiselbuh ◽  
Morris Edelman ◽  
Jeffrey Michael Lipton ◽  
Johnson M. Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Scid Mice ◽  
Cxcr4 Antagonist ◽  
Cell Niche

Abstract Abstract 559 Introduction: Different cellular components of the normal hematopoietic niche have been identified. However, the niche for malignant hematopoiesis remains to be elucidated. Recent work of other groups has suggested that hematopoietic stem cells (HSC) within the bone marrow anchor themselves in place by attaching to osteoblasts and/or vascular sinusoid endothelial cells. We have recently identified mesenchymal stem cells (MSC) as niche-maker cells and found a crucial role of the SDF-1/CXCR4 axis in this process. Stromal Derived Factor-1 (SDF-1/CXCL12) regulates stem cell trafficking and the cell cycle via its receptor CXCR4. Methods: Polyurethane scaffolds, coated in vitro with human bone marrow MSC, were implanted subcutaneously in non-irradiated NOD/SCID mice. CD34+ HSC or primary AML cells (from a leukapheresis product) were injected either in situ or retro-orbitally in the mice and analyzed for engraftment. The mice were treated twice per week with in situ injections of SDF-1, AMD3100 (a CXCR4 antagonist) or PBS (control). After 2 to 4 weeks, the scaffolds were processed and evaluated for cell survival in the mesenchymal niche by immunohistochemistry. Results: We created in vitro MSC-coated scaffolds that retained inoculated AML cells in the presence of SDF-1, while AML cells seeded on empty scaffolds were not retained. In vivo in NOD/SCID mice, the MSC-coated scaffolds, in the presence of SDF-1 enabled homing of both in situ injected normal CD34+ HSC and retroorbital- or in situ injected primary human AML cells. The scaffolds were vascularized and showed osteoclasts and adipocytes present, suggestive of an ectopic human bone marrow microenvironment in the murine host. Finally, the SDF-1-treated scaffolds showed proliferation of the MSC stromal layer with multiple adherent AML cells, while in the AMD3100-treated scaffolds the stromal lining was thin and disrupted at several points, leaving AML cells free floating in proximity. The PBS-treated control-scaffold showed a thin single cell MSC stromal layer without disruption, with few AML cells attached. Conclusion: The preliminary data of this functional ectopic human microenvironment in NOD/SCID mice suggest that AMD3100 (a CXCR4 antagonist) can disrupt the stem cell niche by modulation of the mesenchymal stromal. Further studies are needed to define the role of mesenchymal stem cells in maintaining the hematopoietic/leukemic stem cell niche in vivo. In Vivo Leukemia Stem Cell Niche: (A) Empty polyurethane scaffold. (B)Vascularization in SQ implanted MSC-coated scaffold (s) niche in NOD/SCID mice. (C) DAB Peroxidase (brown) human CD45 positive nests of AML cells (arrows) 1 week after direct in situ AML injection. (D) Human CD45 positive myeloid cells adhere to MSC in vivo (arrows). Disclosures: No relevant conflicts of interest to declare.

In vitro proliferation and differentiation potential of bone marrow-derived mesenchymal stem cells from ovariectomized rats

2014 ◽  
Vol 46 (6) ◽  
pp. 450-456 ◽  
Author(s):  
Ying Gao ◽  
Yanjun Jiao ◽  
Wei Nie ◽  
Bo Lian ◽  
Binquan Wang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Ovariectomized Rats ◽  
In Vitro Proliferation ◽  
Differentiation Potential ◽  
Proliferation And Differentiation

scholarly journals Platelet-Derived Growth Factor Stimulated Migration of Bone Marrow Mesenchymal Stem Cells into an Injectable Gelatin-Hydroxyphenyl Propionic Acid Matrix

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 203
Author(s):  
Wanting Niu ◽  
Teck Chuan Lim ◽  
Abdulmonem Alshihri ◽  
Ravikumar Rajappa ◽  
Lishan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Propionic Acid ◽  
Platelet Derived Growth Factor ◽  
Paracrine Factors ◽  
Proliferation And Differentiation ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (bMSCs) are responsible in the repair of injured tissue through differentiation into multiple cell types and secretion of paracrine factors, and thus have a broad application profile in tissue engineering/regenerative medicine, especially for the musculoskeletal system. The lesion due to injury or disease may be a closed irregular-shaped cavity deep within tissue necessitating an injectable biomaterial permissive of host (endogenous) cell migration, proliferation and differentiation. Gelatin-hydroxyphenyl propionic acid (Gtn-HPA) is a natural biopolymer hydrogel which is covalently cross-linked by horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) in situ and can be delivered to the lesion by needle injection. Growth factors and cytokines can be directly incorporated into the gel or into nano- and micro-particles, which can be employed for sustained release of biomolecules while maintaining their bioactivity. In this study, we selected polyelectrolyte complex nanoparticles (PCNs) prepared with dextran sulfate and chitosan as the carrier for platelet-derived growth factor (PDGF)-BB and stromal cell-derived factor (SDF)-1α, which have been tested effectively in recruiting stem cells. Our in vitro results showed a high degree of viability of bMSCs through the process of Gtn-HPA covalent cross-linking gelation. The Gtn-HPA matrix was highly permissive of bMSC migration, proliferation, and differentiation. PDGF-BB (20 ng/mL) directly incorporated into the gel and, alternatively, released from PCNs stimulated bMSC migration and proliferation. There were only small differences in the results for the direct incorporation of PDGF into the gel compared with its release from PCNs, and for increased doses of the growth factor (200 ng/mL and 2 µg/mL). In contrast, SDF-1α elicited an increase in migration and proliferation only when released from PCNs; its effect on migration was notably less than PDGF-BB. The in vitro results demonstrate that PDGF-BB substantially increases migration of bMSCs into Gtn-HPA and their proliferation in the gel, and that these benefits can be derived from incorporation of a relatively low dose of the growth factor directly into the gel. These findings commend the use of Gtn-HPA/PDGF-BB as an injectable therapeutic agent to treat defects in musculoskeletal tissues.

Cellular Interaction Between Human Mesenchymal Stem Cells and Hematopoietic Stem Cells in 2D- and 3D-Culture-Systems.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1442-1442
Author(s):  
Patrick Wuchter ◽  
Rainer Saffrich ◽  
Annette Ludwig ◽  
Mario Schubert ◽  
Volker Eckstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Cxcr4 Expression ◽  
Cellular Interaction ◽  
Feeder Layer ◽  
Hematopoietic Stem ◽  
Cell Niche

Abstract Abstract 1442 Poster Board I-465 We previously characterized the interaction between human hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) in a 2D-coculture-system and demonstrated that MSC-feeder-layer is capable of maintaining “stemness” in HSC. In order to develop a more physiological in vitro surrogate model for the stem cell niche, we established a 3D-coculture-system using MSC-spheroids. In this model system we analyzed the role of major adhesion molecules such as N-cadherin and the CXCR4/SDF-1 axis upon migration, adhesion and proliferation of HSC. MSC were derived from bone marrow aspirates from healthy voluntary donors. HSC were isolated from umbilical cord blood by magnetic cell sorting of CD34+ mononuclear cells. MSC were cultured as “hanging drops” with initially around 500 cells. Alternatively, MSC were seeded on a layer of 1% agarose in 96 well plates (500-1000 cells per well). In both cases after 24-48h forming of spheroid-like cell aggregations could be observed. Formation of spheroids was obviously independent upon different MSC culture conditions. MSC-spheroids were cocultured with HSC and continuously monitored with time-lapse microscopy. After 24-48 hours of cocultivation, we stained the cellular contacts with a panel of antibodies specific for various components of tight, gap and adherens junctions. Using advanced confocal laser scanning microscopy in combination with deconvolution and volume rendering software, we were able to produce 3D-images of intercellular junctions between HSC and MSC. Additionally, thin sections of the spheroids were analyzed by electron microscopy. In 2D-cocultures, intercellular connections between HSC and MSC are mainly characterized by podia formation of the HSC linking to the adjacent MSC. At the intimate contact zone to the MSC, the cytoplasmic plaque proteins alpha- and beta-catenin, as well as the transmembrane glycoprotein N-cadherin could be identified. Upon 3D-coculture of HSCs with MSC-spheroids, HSCs showed directed locomotion towards MSC-spheroids. After 12h several HSC showed directed locomotion towards MSC-spheroids and connected to the outer cell layer by podia formation. At the contact zone cadherin-catenin-based junctions could be identified. After additional 12-24h a further integration of HSC into the inner mass of the spheroid was observed. Cell division kinetic of HSC was increased when cocultured with MSC and the rate of CD34+ cells remained higher compared to monoculturing of HSC in the same culture-medium. Culturing HSC on MSC feeder-layer resulted in a reduced CXCR4 expression, possibly due to an internalization triggered by direct cell contact to MSC. This novel 3D-setup of an in vitro surrogate model for the human stem cell niche provides deeper inside into the cellular interaction between HSC and stromal cells and demonstrates that direct cellular contact influences cell division kinetics and CXCR4 expression of HSC. Disclosures No relevant conflicts of interest to declare.

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