scholarly journals Mesenchymal Stem Cells Coated with Synthetic Bone-Targeting Polymers Enhance Osteoporotic Bone Fracture Regeneration

2020 ◽  
Vol 7 (4) ◽  
pp. 125
Author(s):  
Yuliya Safarova (Yantsen) ◽  
Farkhad Olzhayev ◽  
Bauyrzhan Umbayev ◽  
Andrey Tsoy ◽  
Gonzalo Hortelano ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Density ◽  
Active Sites ◽  
Bone Fractures ◽  
Bone Fragility ◽  
Female Rats ◽  
Osteoporotic Bone ◽  
Osteoblast Progenitor ◽  
Osteoclastic Activity

Osteoporosis is a progressive skeletal disease characterized by reduced bone density leading to bone fragility and an elevated risk of bone fractures. In osteoporotic conditions, decrease in bone density happens due to the augmented osteoclastic activity and the reduced number of osteoblast progenitor cells (mesenchymal stem cells, MSCs). We investigated a new method of cell therapy with membrane-engineered MSCs to restore the osteoblast progenitor pool and to inhibit osteoclastic activity in the fractured osteoporotic bones. The primary active sites of the polymer are the N-hydroxysuccinimide and bisphosphonate groups that allow the polymer to covalently bind to the MSCs’ plasma membrane, target hydroxyapatite molecules on the bone surface and inhibit osteolysis. The therapeutic utility of the membrane-engineered MSCs was investigated in female rats with induced estrogen-dependent osteoporosis and ulnar fractures. The analysis of the bone density dynamics showed a 27.4% and 21.5% increase in bone density at 4 and 24 weeks after the osteotomy of the ulna in animals that received four transplantations of polymer-modified MSCs. The results of the intravital observations were confirmed by the post-mortem analysis of histological slices of the fracture zones. Therefore, this combined approach that involves polymer and cell transplantation shows promise and warrants further bio-safety and clinical exploration.

Antitumor Effect of Mesenchymal Stem Cells from Murine in Breast Cancer in Female Rats

2018 ◽  
Vol 35 (1) ◽  
pp. 369-374
Author(s):  
Omayma A.R. AbouZaid ◽  
Laila A Rashed ◽  
S. M. El-Sonbaty ◽  
Aboel-Ftouh A. I
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Antitumor Effect ◽  
Female Rats

scholarly journals PP2A in LepR+ mesenchymal stem cells contributes to embryonic and postnatal endochondral ossification through Runx2 dephosphorylation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu-Ting Yen ◽  
May Chien ◽  
Pei-Yi Wu ◽  
Shih-Chieh Hung
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Mesenchymal Stem Cells ◽  
Bone Density ◽  
Endochondral Ossification ◽  
Bone Growth ◽  
Leptin Receptor ◽  
Trabecular Bone Density ◽  
Mature Adipocyte ◽  
Ossification Centers

AbstractIt has not been well studied which cells and related mechanisms contribute to endochondral ossification. Here, we fate mapped the leptin receptor-expressing (LepR+) mesenchymal stem cells (MSCs) in different embryonic and adult extremities using Lepr-cre; tdTomato mice and investigated the underling mechanism using Lepr-cre; Ppp2r1afl/fl mice. Tomato+ cells appear in the primary and secondary ossification centers and express the hypertrophic markers. Ppp2r1a deletion in LepR+ MSCs reduces the expression of Runx2, Osterix, alkaline phosphatase, collagen X, and MMP13, but increases that of the mature adipocyte marker perilipin, thereby reducing trabecular bone density and enhancing fat content. Mechanistically, PP2A dephosphorylates Runx2 and BRD4, thereby playing a major role in positively and negatively regulating osteogenesis and adipogenesis, respectively. Our data identify LepR+ MSC as the cell origin of endochondral ossification during embryonic and postnatal bone growth and suggest that PP2A is a therapeutic target in the treatment of dysregulated bone formation.

scholarly journals The effect of mesenchymal stem cells, demineralized bone graft and platelet-rich plasma on osteogenesis in rat tibia defects

2021 ◽  
Vol 11 (Suppl. 1) ◽  
pp. 47-55
Author(s):  
Zozan Erdoğmuş ◽  
Belgin Gülsün
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Graft ◽  
Platelet Rich Plasma ◽  
Female Rats ◽  
Control Group ◽  
Osteoblastic Activity ◽  
Group I ◽  
Rat Tibia ◽  
Demineralized Bone

Aim: Deformities of the jaw and face are often caused by infection, inflammation, and cystic and neoplastic pathological conditions. Defects with various aetiologies should be repaired promptly using the most appropriate approach to reconstruct the anatomical form. To treat defects, bone grafts with various combinations have been used. In particular, combinations including cellular products to enhance osteogenic properties have been implemented. In this study, we aimed to investigate the effects of different materials and cells on bone defects by using mesenchymal stem cells (MSCs), which are thought to have a positive effect on healing, demineralized bone graft (DMB) and platelet-rich plasma (PRP). Methodology: We used 55 female rats weighing between 200-250 g, four of which were used to obtain platelet-rich plasma. The remaining animals were divided into five groups. Group I (n = 6) was the operative control group, Group II (n = 24) was given DMB, Group III (n = 24) was given DMB+PRP, Group IV (n = 24) was given MSC+DBG and Group V (n = 24) was given DMB+PRP+MSC applied to rat tibial defects (10 mm x 3 mm x 2 mm). Results: Statistically significant differences were observed in bone osteoblastic activity in tibia defects among the groups (p<0.05). Conclusion: Bone regeneration was significantly improved in groups where MSCs were used in combination with DMB and PRP.   How to cite this article: Erdoğmuş Z, Gülsün B. The effect of mesenchymal stem cells, demıneralızed bone graft and platelet-rıch plasma on osteogenesıs ın rat tıbıa defects. Int Dent Res 2021;11(Suppl.1):47-55. https://doi.org/10.5577/intdentres.2021.vol11.suppl1.8   Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.

scholarly journals Osteogenic differentiation of adipose tissue-derived mesenchymal stem cells cultured with different concentrations of prolactin

2017 ◽  
Vol 69 (6) ◽  
pp. 1573-1580
Author(s):  
K.P. Oliveira ◽  
A.M.S. Reis ◽  
A.P. Silva ◽  
C.L.R. Silva ◽  
A.M. Goes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Osteogenic Differentiation ◽  
Bone Sialoprotein ◽  
Collagen I ◽  
Female Rats ◽  
Osteogenic Potential ◽  
Vitro Effect

ABSTRACT The objective was to evaluate the in vitro effect of prolactin in osteogenic potential of adipose tissue-derived mesenchymal stem cells (ADSCs) in female rats. ADSCs were cultured in osteogenic medium with and without the addition of prolactin and distributed into three groups: 1) ADSCs (control), 2) ADSCs with addition of 100ng/mL of prolactin and 3) ADSCs with addition of 300ng/mL of prolactin. At 21 days of differentiation, the tests of MTT conversion into formazan crystals, percentage of mineralized nodules and cells per field and quantification of genic transcript for alkaline phosphatase, osteopontin, osteocalcin, bone sialoprotein, BMP-2 and collagen I by real-time RT-PCR were made. The addition of prolactin reduced the conversion of MTT in group 3 and increased the percentage of cells per field in the groups 2 and 3, however without significantly increasing the percentage of mineralized nodules and the expression of alkaline phosphatase, osteopontin, osteocalcin, bone sialoprotein, BMP-2 and collagen I. In conclusion, the addition of prolactin in concentrations of 100ng/mL and 300ng/mL does not change the osteogenic differentiation to the ADSCs of female rats despite increase in the cellularity of the culture.

scholarly journals Amygdalin Promotes Fracture Healing through TGF-β/Smad Signaling in Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Jun Ying ◽  
Qinwen Ge ◽  
Songfeng Hu ◽  
Cheng Luo ◽  
Fengyi Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fracture Healing ◽  
Bone Fracture ◽  
Transforming Growth Factor ◽  
Bone Fractures ◽  
Conditional Knockout ◽  
Mesenchymal Progenitor Cells ◽  
Bone Fracture Healing ◽  
Smad Signaling

Chondrogenesis and subsequent osteogenesis of mesenchymal stem cells (MSCs) and angiogenesis at injured sites are crucial for bone fracture healing. Amygdalin, a cyanogenic glycoside compound derived from bitter apricot kernel, has been reported to inhibit IL-1β-induced chondrocyte degeneration and to stimulate blood circulation, suggesting a promising role of amygdalin in fracture healing. In this study, tibial fractures in C57BL/6 mice were treated with amygdalin. Fracture calluses were then harvested and subjected to radiographic, histological, and biomechanical testing, as well as angiography and gene expression analyses to evaluate fracture healing. The results showed that amygdalin treatment promoted bone fracture healing. Further experiments using MSC-specific transforming growth factor- (TGF-) β receptor 2 conditional knockout (KO) mice (Tgfbr2Gli1-Cre) and C3H10 T1/2 murine mesenchymal progenitor cells showed that this effect was mediated through TGF-β/Smad signaling. We conclude that amygdalin could be used as an alternative treatment for bone fractures.

The Effect of Mesenchymal Stem Cells as a Cell Therapy in Renal Ischemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4756-4756
Author(s):  
Dae Sik Hong ◽  
Seongkyu Park ◽  
Jong-Ho Won ◽  
Chan Kyu Kim ◽  
Sang Chul Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Renal Failure ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Y Chromosome ◽  
Renal Injury ◽  
Female Rats ◽  
Sprague Dawley ◽  
Creatinine Concentration ◽  
Histologic Evaluation

Abstract Introduction: The most commonly used therapeutic targets in nephrology are the reduction of injury, the delay of progression, or renal replacement therapy. Many animal and human studies demonstrated the role of stem cells in repair and regenerations of kidney. Mesenchymal stem cells (MSCs) have shown to improve outcome of acute renal injury models. It is controversial whether MSCs can reduce injury following a toxic/ischemic event and delay renal failure in chronic kidney disease. We evaluated the hypothesis that the treatment with MSCs could improve renal function and attenuate injury in chronic renal failure (CRF). Materials and methods: Sprague-Dawley female rats (8 weeks old, 182.2 ± 7.2g) were underwent modified 5/6 nephrectomy. Rats in the MSC group received an injection of MSCs (1 × 106 cells) via tail vein 1 day after nephrectomy. Blood and urine samples were collected after 7 days and every month thereafter. The kidneys of rats were removed for histologic evaluation after 24-hr urine collection and blood sampling. The Y-chromosome stain using fluorescent in situ hybridization was performed to verify the presence of male MSCs in the kidney of female recipients. Results: No significant differences in blood urea nitrogen and creatinine concentration were observed between MSC group and untreated CRF group. However, the weight gain and creatinine clearance in the MSC group were greater than those of the CRF group. Proteinuria in the MSC group was less after 4 months. Y chromosome was detected in the kidney of MSC group. Although no significances were observed between two groups, the histologic analysis suggests that MSCs have positive effect against glomerulosclerosis. Conclusions: These results suggest that MSCs help preserve renal function and attenuate renal injury in CRF.

scholarly journals PROLONGED LIFESPAN OF AGING RAT AFTER XENOTRANPLANTATION OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS (hUC-MSCs)

2020 ◽  
Vol 21 (4) ◽  
pp. 539-549
Author(s):  
Elpita Tarigan ◽  
Adisti Dwijayanti ◽  
Frans Dhyanagiri Suyatna ◽  
Indra Bachtiar ◽  
Sandy Qlintang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Body Weight ◽  
Blood Chemistry ◽  
Blood Analysis ◽  
Female Rats ◽  
Human Umbilical Cord ◽  
Female Rat ◽  
Aging Rat ◽  
Before And After

Currently, mesenchymal stem cells (MSCs) for implementing regenerative medicine in aging become interest in medical research science, especially in degerative disease and other aging problems. This research was aimed to determine the effectiveness of hUC-MSCs on inhibiting the aging process through the lifetime of the rat and the effect of intravenous administration of hUC-MSCs in phisiologycally aging female rat on the blood analysis. This study was used 40 aged female rats with 29-30 months of age divided into four groups with 10 rats each. The control rat group was given physiological NaCl (0.9%) 0.5 mL, and the treated rat group was given hUC-MSCs 1x107 cells/kg body weight in 0.5 mL NaCl 0.9%, was injected intravenously in caudo lateralis tail vein with stratified frequency; one time injection (SC1), three times injections (SC3) and five times injections (SC5). Perifer blood was collected from retro-ortbital sinus vein 30 days before and after injection of hUC-MSCs for hematology and blood chemistry analysis. Based on the results were obtained, it indicated that hUC-MSCs increased the survival of aging rat were in treatment group, life span of rats was extended up to 40 months compared to the average life of control rat aged up to 34±2 months. The injection of hUC-MSCs 1x107 cells/kg of body weight with one, three and five times injection were affected to blood profiles and blood chemistry with correlation were low. The conclusions are hUC-MSCs extend the lifespan of aging rat and were affect the blood in general but in normal range of aging rat, affect in ALT and creatinin as tissue repair and tolerated by aging rat.

scholarly journals Loss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin

2020 ◽  
Vol 28 (1) ◽  
pp. 156-169
Author(s):  
Tania Velletri ◽  
Yin Huang ◽  
Yu Wang ◽  
Qing Li ◽  
Mingyuan Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Density ◽  
Osteogenic Differentiation ◽  
Bone Remodeling ◽  
Bone Homeostasis ◽  
Loss Of Function ◽  
P53 Expression ◽  
Receptor Activator

Abstractp53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53+/+, p53+/−, and p53−/− mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling.

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