scholarly journals Coordinated Regulation of Mesenchymal Stem Cell Migration by Various Chemotactic Stimuli

2020 ◽  
Vol 21 (22) ◽  
pp. 8561
Author(s):  
Donghyun Nam ◽  
Aran Park ◽  
Maria Jose Dubon ◽  
Jinyeong Yu ◽  
Wootak Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mouse Bone Marrow ◽  
Functional Interactions ◽  
Combination Treatments

Endogenous bone marrow-derived mesenchymal stem cells are mobilized to peripheral blood and injured tissues in response to changes in the expression of various growth factors and cytokines in the injured tissues, including substance P (SP), transforming growth factor-beta (TGF-β), and stromal cell-derived factor-1 (SDF-1). SP, TGF-β, and SDF-1 are all known to induce the migration of bone marrow-derived mesenchymal stem cells (BM-MSCs). However, it is not yet clear how these stimuli influence or interact with each other during BM-MSC mobilization. This study used mouse bone marrow-derived mesenchymal stem cell-like ST2 cells and human BM-MSCs to evaluate whether SP, TGF-β, and SDF-1 mutually regulate their respective effects on the mobilization of BM-MSCs. SP pretreatment of ST2 and BM-MSCs impaired their response to TGF-β while the introduction of SP receptor antagonist restored the mobilization of ST2 and BM-MSCs in response to TGF-β. TGF-β pretreatment did not affect the migration of ST2 and BM-MSCs in response to SP, but downregulated their migration in response to SDF-1. SP pretreatment modulated the activation of TGF-β noncanonical pathways in ST2 cells and BM-MSCs, but not canonical pathways. These results suggest that the migration of mesenchymal stem cells is regulated by complex functional interactions between SP, TGF-β, and SDF-1. Thus, understanding the complex functional interactions of these chemotactic stimuli would contribute to ensuring the development of safe and effective combination treatments for the mobilization of BM-MSCs.

scholarly journals Cytotoxic Effect of Hypoxic Environment in Mesenchymal Stem Cell

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1592
Author(s):  
Sevil Özer ◽  
H. Seda Vatansever ◽  
Feyzan Özdal-Kurt
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Human Mesenchymal Stem Cells ◽  
Hypoxic Condition ◽  
Immunoperoxidase Technique ◽  
Cellular Functions ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BM-MSCs) are used to repair hypoxic or ischemic tissue. After hypoxic the level of ATP is decreases, cellular functions do not continue and apoptosis or necrosis occur. Apoptosis is a progress of programmed cell death that occurs in normal or pathological conditions. In this study, we were investigated the hypoxic effect on apoptosis in mesenchymal stem cell. Bone marrow-derived stem cells were cultured in hypoxic (1% or 3%) or normoxic conditions 24, 96 well plates for 36 h. Cell viability was shown by MTT assay on 36 h. After fixation of cells with 4% paraformaldehyde, distributions of caspase-3, Bcl-2 and Bax with indirect immunoperoxidase technique, apoptotic cells with TUNEL assay were investigated. All staining results were evaluated using H-score analyses method with ANOVA, statistically. As a result, hypoxic condition was toxic for human mesenchymal stem cells and the number of death cell was higher in that than normoxic condition.

microRNA-265 Regulates Bone Marrow Mesenchymal Stem Cells Differentiation and Promotes Sepsis Lung Injury Repair via Transforming Growth Factor Beta 1

2022 ◽  
Vol 12 (2) ◽  
pp. 405-410
Author(s):  
Lian Tan ◽  
Xiongxiong Wang ◽  
Danqi Chen ◽  
Li Xu ◽  
Yudong Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Lung Injury ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Alveolar Type ◽  
Injury Repair ◽  
Qrt Pcr ◽  
Marrow Mesenchymal Stem Cells

Our study investigates whether miR-265 regulates the differentiation of rat bone marrow mesenchymal stem cells (BMSCs) into alveolar type II epithelial cells (ATII) through TGF-β1 and promotes lung injury repair in rats with sepsis, thereby inhibiting sepsis progression. 25 patients with sepsis admitted to the Respiratory and Critical Care Medicine Department of the hospital and 17 normal controls were included. TGF-β1 level was measured by ELISA. miR-265 level was measured by qRT-PCR and AT II-related genes and proteins expression was analyzed by western blot and qRT-PCR. miR-265 expression was significantly higher in sepsis patients than normal group. Progenitor BMSCs were long and shuttle-shaped after 1 and 3 days of growth. Cultured MSCs had low expression of the negative antigen CD34 (4.32%) and high expression of the positive antigen CD44 (99.87%). TGF-β1 level was significantly increased with longer induction time, while miR-265 expression was significantly decreased in cell culture medium. miR-265 interference significantly decreased TGF-β1 expression. In conclusion, miR-265 inhibits BMSC differentiation to AT II via regulation of TGF-β1, thereby inhibiting sepsis progression.

PRECONDITIONING MESENCHYMAL STEM CELLS WITH TRANSFORMING GROWTH FACTOR-ALPHA IMPROVES MESENCHYMAL STEM CELL-MEDIATED CARDIOPROTECTION

Shock ◽  
2010 ◽  
Vol 33 (1) ◽  
pp. 24-30 ◽  
Author(s):  
Jeremy L. Herrmann ◽  
Yue Wang ◽  
Aaron M. Abarbanell ◽  
Brent R. Weil ◽  
Jiangning Tan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Mesenchymal Stem Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Alpha ◽  
Factor Alpha

scholarly journals GDF11 enhances therapeutic functions of mesenchymal stem cells for angiogenesis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chi Zhang ◽  
Yinuo Lin ◽  
Ke Zhang ◽  
Luyang Meng ◽  
Xinyang Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Lentiviral Vector ◽  
Retention Rate ◽  
Antibody Array ◽  
Mouse Bone Marrow ◽  
Control Mscs

Abstract Background The efficacy of stem cell therapy for ischemia repair has been limited by low cell retention rate. Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β super family, which has multiple effects on development, physiology and diseases. The objective of the study is to investigate whether GDF11 could affect the efficacy of stem cell transplantation. Methods We explored the effects of GDF11 on proangiogenic activities of mesenchymal stem cells (MSCs) for angiogenic therapy in vitro and in vivo. Results Mouse bone marrow-derived MSCs were transduced with lentiviral vector to overexpress GDF11 (MSCGDF11). After exposed to hypoxia and serum deprivation for 48 h, MSCGDF11 were significantly better in viability than control MSCs (MSCvector). MSCGDF11 also had higher mobility and better angiogenic paracrine effects. The cytokine antibody array showed more angiogenic cytokines in the conditioned medium of MSCGDF11 than that of MSCvector, such as epidermal growth factor, platelet-derived growth factor-BB, placenta growth factor. When MSCs (1 × 106 cells in 50 μl) were injected into ischemic hindlimb of mice after femoral artery ligation, MSCGDF11 had higher retention rate in the muscle than control MSCs. Injection of MSCGDF11 resulted in better blood reperfusion and limb salvage than that of control MSCs after 14 days. Significantly more CD31+ endothelial cells and α-SMA + smooth muscle cells were detected in the ischemic muscles that received MSCGDF11. The effects of GDF11 were through activating TGF-β receptor and PI3K/Akt signaling pathway. Conclusion Our study demonstrated an essential role of GDF11 in promoting therapeutic functions of MSCs for ischemic diseases by enhancing MSC viability, mobility, and angiogenic paracrine functions.

Application of Bone Marrow–Derived Mesenchymal Stem Cells for Muscle Healing After Contusion Injury in Mice

2020 ◽  
Vol 48 (5) ◽  
pp. 1226-1235 ◽  
Author(s):  
Chih-Hao Chiu ◽  
Tsan-Hsuan Chang ◽  
Shih-Sheng Chang ◽  
Gwo-Jyh Chang ◽  
Alvin Chao-Yu Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Mesenchymal Stem Cell Therapy ◽  
Contusion Injury ◽  
Fast Twitch

Background: Skeletal muscle injuries are very common in sports medicine. Conventional therapies have limited clinical efficacy. New treatment methods should be developed to allow athletes to return to play with better function. Purpose: To evaluate the in vitro differentiation potential of bone marrow–derived mesenchymal stem cells and the in vivo histologic and physiologic effects of mesenchymal stem cell therapy on muscle healing after contusion injury. Study Design: Controlled laboratory study. Methods: Bone marrow cells were flushed from both femurs of 5-week-old C57BL/6 mice to establish immortalized mesenchymal stem cell lines. A total of 36 mice aged 8 to 10 weeks were used to develop a muscle contusion model and were divided into 6 groups (6 mice/group) on the basis of the different dosages of IM2 cells to be injected (0, 1.25 × 105, and 2.5 × 105 cells with/without F-127 in 100 μL of phosphate-buffered saline). Histological analysis of muscle regeneration was performed, and the fast-twitch and tetanus strength of the muscle contractions was measured 28 days after muscle contusion injury, after injections of different doses of mesenchymal stem cells with or without the F-127 scaffold beginning 14 days after contusion injury. Results: The mesenchymal stem cell–treated muscles exhibited numerous regenerating myofibers. All the groups treated with mesenchymal stem cells (1.25 × 105 cells, 2.5 × 105 cells, 1.25 × 105 cells plus F-127, and 2.5 × 105 cells plus F-127) exhibited a significantly higher number of regenerating myofibers (mean ± SD: 111.6 ± 14.77, 133.4 ± 21.44, 221.89 ± 32.65, and 241.5 ± 25.95, respectively) as compared with the control group and the control with F-127 (69 ± 18.79 and 63.2 ± 18.98). The physiologic evaluation of fast-twitch and tetanus strength did not reveal differences between the age-matched uninjured group and the groups treated with various doses of mesenchymal stem cells 28 days after contusion. Significant differences were found between the control group and the groups treated with various doses of mesenchymal stem cells after muscle contusion. Conclusion: Mesenchymal stem cell therapy increased the number of regenerating myofibers and improved fast-twitch and tetanus muscle strength in a mouse model of muscle contusion. However, the rapid decay of transplanted mesenchymal stem cells suggests a paracrine effect of this action. Treatment with mesenchymal stem cells at various doses combined with the F-127 scaffold is a potential therapy for a muscle contusion. Clinical Relevance: Mesenchymal stem cell therapy has an effect on sports medicine because of its effects on myofiber regeneration and muscle strength after contusion injury.

scholarly journals Effect of Lactoferrin on the Expression Profiles of Long Non-coding RNA during Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells

2019 ◽  
Vol 20 (19) ◽  
pp. 4834 ◽  
Author(s):  
Yan Xu ◽  
Jing-Jing An ◽  
Dina Tabys ◽  
Yin-Dan Xie ◽  
Tian-Yu Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Expression Profiles ◽  
Bioinformatic Analysis ◽  
Marrow Mesenchymal Stem Cells ◽  
The Impact

Lactoferrin (LF) has demonstrated stimulation of osteogenic differentiation of mesenchymal stem cells (MSCs). Long non-coding RNAs (lncRNAs) participate in regulating the osteogenic differentiation processes. However, the impact of LF on lncRNA expression in MSC osteogenic differentiation is poorly understood. Our aim was to investigate the effects of LF on lncRNAs expression profiles, during osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), by RNA sequencing. A total number of 1331 putative lncRNAs were identified in rBMSCs during osteogenic differentiation in the study. LF influenced the expression of 120 lncRNAs (differentially expressed lncRNAs [DELs], Fold change > 1.5 or < −1.5; p < 0.05) in rBMSCs on day 14 of osteogenic differentiation, consisted of 60 upregulated and 60 down-regulated. Furthermore, the potential functions of DELs were of prediction by searching their target cis- and trans-regulated protein-coding genes. The bioinformatic analysis of DELs target gene revealed that LF led to the disfunction of transforming growth factor beta stimulus (TGF-β) and positive regulation of I-κappa B kinase/NF-κappa B signaling pathway, which may relate to osteogenic differentiation of rBMSCs. Our work is the first profiling of lncRNA in osteogenic differentiation of rBMSCs induced by LF, and provides valuable insights into the potential mechanisms for LF promoting osteogenic activity.

Use of mesenchymal stem cells from adult bone marrow for injured tissue repair

2009 ◽  
Vol 150 (27) ◽  
pp. 1259-1265 ◽  
Author(s):  
Antal Salamon ◽  
Erzsébet Toldy
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Transforming Growth Factor Beta ◽  
Tissue Repair ◽  
Transforming Growth Factor ◽  
Injured Tissue ◽  
Growth Factor Beta ◽  
Adult Bone

A csontvelőből származó mesenchymalis őssejtek pluripotensek, s képesek porc, csont, valamint adiposus és ínsejtekké differenciálódni. Ezen mesenchymalis progenitor sejteket stromasejteknek vagy mesenchymalis őssejteknek nevezik. A csontvelőben két fő sejttípus van: haematopoeticus sejt és stromasejt. Mesenchymalis őssejtek kis beavatkozással nyerhetők a csontvelőből, majd sejtkultúrában szaporíthatóak. Differenciálódásuk bioaktív molekulákkal, specifikus növekedési faktorokkal segíthető elő. A transforming growth factor beta (TGF-β) család tagjai proteinek, közülük a bone morphogenetic proteinek (BMP) a legfontosabb faktorok, amelyek elősegítik a mesenchymalis őssejtek porc- és csontszövetté történő differenciálódását. Kevésbé ismert még ezen sejteknek a tenogenesisben való szerepe, de már vannak biztató adatok e téren is. A mesenchymalis őssejteknek és növekedési faktoroknak a sérült szövetekbe való juttatásra vivő vázanyagra (carrier, scaffold) van szükség. Mesenchymalis őssejtek használhatók fel génterápiára és a tissue engineering alkalmazására. A szerzők jelen munkájukban áttekintik a mesenchymalis őssejtek, biomolekulák és növekedési faktorok szövetpótlás céljából történő használatával foglalkozó kísérletes vizsgálatok eddigi eredményeit és ismertetik a klinikai alkalmazás lehetőségeit.

scholarly journals Mesenchymal stem cells targeting PI3K/AKT pathway in leukemic model

Tumor Biology ◽  
2019 ◽  
Vol 41 (4) ◽  
pp. 101042831984680 ◽  
Author(s):  
Esraa S A Ahmed ◽  
Neamat H Ahmed ◽  
Amina M Medhat ◽  
Ussama Z Said ◽  
Laila A Rashed ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
B Cell ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cell Lymphoma ◽  
Hematological Parameters ◽  
B Cell Lymphoma

Mesenchymal stem cells have therapeutic properties that are related to their potentials for trans-differentiation, immunomodulation, anti-inflammatory, inhibitory effect on tumor proliferation, and induction of apoptosis. This study was performed to analyze the role of mesenchymal stem cells as an alternative for cellular signaling growth factors involved in the pathogenesis of leukemogenesis in rats. Treatment of rats with 7,12-dimethyl benz [a] anthracene induced leukemogenesis appeared as a significant decrease in hematological parameters with concomitant significant increase in bone marrow oxidative and inflammatory indices (transforming growth factor beta and interleukin-6) in comparison with normal groups. On the contrary, Western immunoblotting showed a significant increase in the signaling growth factors: PI3K, AKT, mTOR proteins and a significant decrease in PTEN in 7,12-dimethyl benz [a] anthracene–treated group. In addition, a significant increase in the transcript levels of B cell lymphoma-2 protein gene in the 7,12-dimethyl benz [a] anthracene group, while that of C-X-C motif chemokine receptor-4 and B cell lymphoma-2 protein associated x-protein were significantly downregulated compared to controls. Meanwhile, therapeutic mesenchymal stem cells treatment predict a significant improvement versus 7,12-dimethyl benz [a] anthracene group through the modulation of growth factors that confront bone marrow dysplasia. In the same direction treatment of 7,12-dimethyl benz [a] anthracene group with mesenchymal stem cells, it induced apoptosis and increased the homing efficacy to bone marrow. In conclusion, mesenchymal stem cells improve hematopoiesis and alleviate inflammation, and modulated PI3K/AKT signaling pathway contributed to experimental leukemogenesis.

Mesenchymal stem cells may ameliorate inflammation in an ex vivo model of extracorporeal membrane oxygenation

Perfusion ◽  
2019 ◽  
Vol 34 (1_suppl) ◽  
pp. 15-21 ◽  
Author(s):  
Viktor von Bahr ◽  
Jonathan E Millar ◽  
Maximillian V Malfertheiner ◽  
Katrina K Ki ◽  
Margaret R Passmore ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Growth Factor ◽  
Mesenchymal Stem Cell ◽  
Extracorporeal Membrane Oxygenation ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Transforming Growth Factor Β1 ◽  
Membrane Oxygenation

Introduction: Mesenchymal stem cells exhibit immunomodulatory properties which are currently being investigated as a novel treatment option for Acute Respiratory Distress Syndrome. However, the feasibility and efficacy of mesenchymal stem cell therapy in the setting of extracorporeal membrane oxygenation is poorly understood. This study aimed to characterise markers of innate immune activation in response to mesenchymal stem cells during an ex vivo simulation of extracorporeal membrane oxygenation. Methods: Ex vivo extracorporeal membrane oxygenation simulations (n = 10) were conducted using a commercial extracorporeal circuit with a CO2-enhanced fresh gas supply and donor human whole blood. Heparinised circuits (n = 4) were injected with 40 × 106-induced pluripotent stem cell–derived human mesenchymal stem cells, while the remainder (n = 6) acted as controls. Simulations were maintained, under physiological conditions, for 240 minutes. Circuits were sampled at 15, 30, 60, 120 and 240 minutes and assessed for levels of interleukin-1β, interleukin-6, interleukin-8, interleukin-10, tumour necrosis factor-α, transforming growth factor-β1, myeloperoxidase and α-Defensin-1. In addition, haemoglobin, platelet and leukocyte counts were performed. Results: There was a trend towards reduced levels of pro-inflammatory cytokines in mesenchymal stem cell–treated circuits and a significant increase in transforming growth factor-β1. Blood cells and markers of neutrophil activation were reduced in mesenchymal stem cell circuits during the length of the simulation. As previously reported, the addition of mesenchymal stem cells resulted in a reduction of flow and increased trans-oxygenator pressures in comparison to controls. Conclusions: The addition of mesenchymal stem cells during extracorporeal membrane oxygenation may cause an increase in transforming growth factor-β1. This is despite their ability to adhere to the membrane oxygenator. Further studies are required to confirm these findings.

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