scholarly journals Use of paracrine factors from stem cells to treat local radiation burns in rats

2018 ◽  
Vol Volume 11 ◽  
pp. 69-76
Author(s):  
A Temnov ◽  
T Astrelina ◽  
Konstantin Rogov ◽  
B Moroz ◽  
Vladimir Lebedev ◽  
...  
Keyword(s):  
Stem Cells ◽  
Paracrine Factors ◽  
Local Radiation

Investigation of the Influence of the Conditioning Medium Factors Obtained During the Cultivation of Bone Marrow Mesenchymal Stem Cells on the Course of Severe Local Radiation Injuries of Skin in Rats

2018 ◽  
Vol 63 (1) ◽  
pp. 35-43 ◽  
Author(s):  
А. Темнов ◽  
A. Temnov ◽  
Т. Астрелина ◽  
T. Astrelina ◽  
К. Рогов ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Skin Lesion ◽  
Conditioned Medium ◽  
Radiation Injuries ◽  
Lesion Area ◽  
Paracrine Factors ◽  
Local Radiation ◽  
Radiation Ulcers

Purpose: Study of the effect of paracrine factors, produced by MMSC of bone marrow during the cultivation, on the severity of local radiation injuries in the conditions of application in the early periods after irradiation. Material and methods: Experiments were performed on rats of the breed Wistar weighing 280 g. Rats were exposed locally in iliolumbar region of the back using X-ray machine LNC-268 (RAP 100-10) at a dose of 110 Gy (30 kV tube voltage, current 6.1 mA, filter Al 0.1 mm thick), dose rate is 21.4 Gy/min. Area of the irradiation field was 8.2–8.5 cm2. The conditioned medium obtained by culturing MMSC of rats’ bone marrow was administered in dose 1.0 ml (total protein 8 mg/ml) at 1, 3, 6, 8 and 10 days after irradiation. The severity of radiation damage to the skin and the effects of therapy were evaluated in dynamics by clinical manifestations, using planimetry and histological methods. Results: It was shown that in control animals and in rats, with the introduction of the conditioned medium, the values of the skin lesion area in the period up to the 29th day after irradiation practically did not differ, gradually decreasing in control animals from 5.9 ± 0.6 cm2 to 2.2 ± 0.3 cm2 at the 15th and 29th days after irradiation, respectively. Then, in the control group, the lesion area ranged from 1.4 ± 0.6 cm2 on the 50th day to 1.9 ± 0.8 cm2 on the 71st day. In the experimental group of animals, with the introduction of factors of the conditioning medium, a decrease in the area of the lesion and a stable dynamics of healing of radiation ulcers, beginning from the 36th day, there was a gradual decrease in the area of the lesion, which reached 0.2 ± 0.1 cm2 by the 71st day after irradiation. On the 64–71th day after irradiation, the difference between the areas of skin lesion in the experimental and control groups was statistically significant, p <0.05. The histological analysis showed that the use of paracrine factors obtained from MMSC in the process of cultivation significantly reduces the severity of the inflammatory reaction and accelerates the regeneration processes. Conclusion: Thus, the introduction of conditioned medium factors obtained during the cultivation of mesenchymal stem cells of the bone marrow facilitates a more easy flow of the pathological process and the healing of radiation ulcers after local radiation damage to the skin of rats. Apparently, the favorable effect of paracrine factors introduced in the early periods after irradiation, with severe local radiation injuries, is associated with their effect on pathological processes in the inflammatory-destructive stage.

The Influence of Mesenchymal Stem Cells of Adipose Tissue and Paracrine Factors of Conditioned Medium on the Healing of Radiation Ulcers in the Treatment of Severe Radiation Injuries of Skin in Rats

2021 ◽  
Vol 66 (2) ◽  
pp. 5-12
Author(s):  
V Lebedev ◽  
Yu. Deshevoy ◽  
A. Temnov ◽  
T. Astrelina ◽  
K. Rogov ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Conditioned Medium ◽  
Control Group ◽  
X Rays ◽  
Radiation Injuries ◽  
Paracrine Factors ◽  
Local Radiation ◽  
Radiation Ulcers

Purpose: Studying of the effects transplantation of cultured mesenchymal stem cells of adipose tissue (MMSC) and adipose-derived stromal vascular fraction (SVF), as well as the introduction of paracrine factors (PF) of conditioned medium in an isolated or combined application for severe local radiation skin lesions in the experiment. Material and methods: Rats of the inbred Wistar–Kyoto strain were irradiated to local X-rays exposure in the iliolumbar region of the back at a dose of 110 Gy. The transplantation of cultured MMSC was performed twice at doses of 2.1 × 106 and 2.6 × 106 on the 28th and 35th days after irradiation. Adipose-derived SVF was administered at the same time in doses of 3.2 × 106 and 2.8 × 106, respectively. PF were administered five times from the 1st to the 10th day after irradiation. The severity of radiation damage to the skin and the effects of therapy were evaluated in dynamics by clinical manifestations, using planimetry and histological methods. Results: Radiation exposure with these parameters caused severe radiation injuries of the skin with non-healing ulcers formed by the 21–25th day after irradiation. The area of radiation ulcers in rats of the control group in the period from the 26th to the 83rd day slowly decreased from 2.76 ± 0.12 cm2 to 1.85 ± 0.13 cm2. In 50 % of the animals in the control group, ulcers persisted for more than 4 months after irradiation. In rats of the experimental groups, more intensive healing and a decrease in the area of radiation ulcers was noted. With isolated administration of cultured MMSC or SVF, a statistically significant decrease in the area of ulcers compared with the control was observed on the 104–125th day, and with the introduction of PF on the 83rd day after irradiation, p <0.05. In the control group, by the118th day after irradiation, radiation ulcers healed only in 25 % of rats, and in the experimental groups with isolated administration of cultured MMSC, SVF and PF in 40–55 % of the rats showed complete epithelialization of wounds with the formation of an atrophic scar. Under the conditions of combined use of stem cells and conditioned medium factors, the number of animals with complete healing of radiation ulcers was 85–100 % by 118th days, p <0.05. Conclusion: Thus, transplantation of cultured MMSC of adipose tissue and adipose-derived SVF, as well as the introduction of PF of conditioned medium, can enhance the regeneration processes and stimulate skin regeneration, promoting earlier healing of chronic radiation ulcers in severe local radiation injuries. Moreover, with the combined introduction of PF and adipose-derived stem cell transplantation, the effectiveness of the healing of radiation ulcers was increases.

scholarly journals Adropin-based dual treatment enhances the therapeutic potential of mesenchymal stem cells in rat myocardial infarction

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
HuiYa Li ◽  
DanQing Hu ◽  
Guilin Chen ◽  
DeDong Zheng ◽  
ShuMei Li ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Paracrine Factors ◽  
Dual Treatment

AbstractBoth weak survival ability of stem cells and hostile microenvironment are dual dilemma for cell therapy. Adropin, a bioactive substance, has been demonstrated to be cytoprotective. We therefore hypothesized that adropin may produce dual protective effects on the therapeutic potential of stem cells in myocardial infarction by employing an adropin-based dual treatment of promoting stem cell survival in vitro and modifying microenvironment in vivo. In the current study, adropin (25 ng/ml) in vitro reduced hydrogen peroxide-induced apoptosis in rat bone marrow mesenchymal stem cells (MSCs) and improved MSCs survival with increased phosphorylation of Akt and extracellular regulated protein kinases (ERK) l/2. Adropin-induced cytoprotection was blocked by the inhibitors of Akt and ERK1/2. The left main coronary artery of rats was ligated for 3 or 28 days to induce myocardial infarction. Bromodeoxyuridine (BrdU)-labeled MSCs, which were in vitro pretreated with adropin, were in vivo intramyocardially injected after ischemia, following an intravenous injection of 0.2 mg/kg adropin (dual treatment). Compared with MSCs transplantation alone, the dual treatment with adropin reported a higher level of interleukin-10, a lower level of tumor necrosis factor-α and interleukin-1β in plasma at day 3, and higher left ventricular ejection fraction and expression of paracrine factors at day 28, with less myocardial fibrosis and higher capillary density, and produced more surviving BrdU-positive cells at day 3 and 28. In conclusion, our data evidence that adropin-based dual treatment may enhance the therapeutic potential of MSCs to repair myocardium through paracrine mechanism via the pro-survival pathways.

Abstract 362: Proteomic Analysis of Low Oxygen Tension-Induced Secretome of Adipose Tissue-Derived Stem Cells

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Zeljko Bosnjak ◽  
Bassam Wakim ◽  
Yasheng Yan ◽  
Scott Canfield ◽  
Chika Kikuchi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Oxygen Tension ◽  
Proteomic Analysis ◽  
Stem Cell Markers ◽  
Paracrine Factors ◽  
Differentiation Potential ◽  
Trophic Effect ◽  
Lower Oxygen

Growing evidence from animal studies shows that adipose tissue-derived stem cells (ASCs) improve cardiac function of infarcted hearts. It is commonly accepted that therapeutic potential of ASCs may depend more on their paracrine effects than differentiation potential. The underlying mechanisms remain unclear. However, most data regarding paracrine factors were obtained from ASCs cultured in normoxic condition (20%). The present study investigated how in vivo physiological oxygen (4%) tension influenced the secretome of ASCs. ASCs were isolated from three 8-week-old BALB/c mice. ASCs were confirmed by the expression of stem cell markers (CD44 and CD90) and their capacity to differentiate into adipocytes and osteocytes. ASCs at passage 5 were cultured in normoxic (20%) and lower oxygen (4%) incubators and conditioned for 24 h (3 cultures/group). The conditioned media (CM) from ASCs were subjected to trypsin digestion followed by analysis using automated nano-flow liquid chromatography tandem mass spectrometry. The collected LC/MS/MS data were searched against the rodent subset of the Uniprot database and the total proteomes were identified. The data were from 6 technical replicates. A total of 28 proteins were identified and 7 proteins were unique to normoxic CM. Of the 21 common proteins detected in both normoxic and lower oxygen CM, 9 were extracellular matrix proteins. The abundance of 6 of these proteins (e.g., collagen I and laminin) differed noticeably between normoxic and lower oxygen CM. In addition, a greater amount of cytokine CXCL5 and matrix metalloproteinase (MMP)-2 was detected in lower oxygen CM than in normoxic CM while tissue inhibitor of metalloproteinase (TIMP)-1 was only detected in normoxic CM. These results indicate that lower oxygen tension differentially regulates the secretome of ASCs. Extrapolating the results of this study to the in vivo setting, it would appear that injected ASCs may exert their anti-fibrotic and trophic effect by 1) directly regulating the balance of MMP/TIMP production and preventing collagen accumulation in ischemic hearts to decrease fibrosis, and 2) secreting trophic factors including CXCL5. These data suggest that proteomic analysis of CM is useful for elucidation of the paracrine effect of ASCs in vivo.

Abstract 329: Discovery of a Novel Paracrine Angiogenic Factor from Akt-Transduced Mesenchymal Stem Cells for Cell/Protein-based Therapy in angiogenesis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Jian Guo ◽  
Jing Huang ◽  
Maria Mirotsou ◽  
Hui Mu ◽  
Lunan Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Fusion Proteins ◽  
Stop Codon ◽  
Umbilical Vein ◽  
Hek293 Cells ◽  
Angiogenic Factor ◽  
Cell Protein ◽  
Paracrine Factors ◽  
Novel Transcripts

Previously we have shown that injection of mesenchymal stem cells overexpressing the survival gene Akt (Akt-MSCs) into infarcted rodent hearts dramatically reduced the infarct size and improved ventricular function as early as 72 hours after treatment. Furthermore, injection of conditioned medium isolated from these cells reproduced the similar effects. These data strongly suggest that the observed beneficial effects are due to paracrine factors released from the Akt-MSCs. Since angiogenesis has been shown previously to reduce ischemia injury, we reasoned that part of the protective effects include an angiogenic component. To help identify potential paracrine factors, we performed microarray analysis of Akt-MSCs and identified 46 novel differentially expressed transcripts, and among these, 5 novel transcripts potentially encoding secreted proteins were identified. The open reading frames of these novel transcripts were cloned and expressed in E. coli as maltose binding protein (MBP) fusion proteins. These 5 novel MBP fusion proteins (10nM) were tested in an endothelial tube formation assay using Human Umbilical Vein Endothelial Cells (HUVECs). Compared to MBP control or fresh serum free media, one of the MBP-novel fusion proteins has a pronounced tube forming ability (n = 8, p < 0.001). Bioinformatic analysis reveals that this novel angiogenic factor contains two fibronectin type III domains and a short hydrophobic ~20 amino acid as the signal peptide at amino-terminus. Full-length human cDNA (1704 base pairs) of this novel angiogenic factor was cloned into pcDNA-DEST40 plasmid without the stop codon, in the translational frame fused with V5-epitope at the carboxyl terminus. Upon transient transfection into HEK293 cells with this expression construct, this novel angiogenic factor secreted into culture medium as ~63 KDa protein evidenced by western blotting using anti-V5 antibody. Further studies will dissect the signaling mechanisms of this novel factor and our ongoing in vivo studies will further explore the possibilities of using protein and/or cell-based approach for novel therapeutic angiogenesis for the injured heart.

scholarly journals Analyzing Impetus of Regenerative Cellular Therapeutics in Myocardial Infarction

2020 ◽  
Vol 9 (5) ◽  
pp. 1277 ◽  
Author(s):  
Ming-Long Chang ◽  
Yu-Jui Chiu ◽  
Jian-Sing Li ◽  
Khoot-Peng Cheah ◽  
Hsiu-Hu Lin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Cardiac Fibroblasts ◽  
Cell Lineage ◽  
Specific Cell ◽  
Paracrine Factors ◽  
Differentiation Potential ◽  
Cell Based Therapy ◽  
Organ Specific ◽  
Made In

Both vasculature and myocardium in the heart are excessively damaged following myocardial infarction (MI), hence therapeutic strategies for treating MI hearts should concurrently aim for true cardiac repair by introducing new cardiomyocytes to replace lost or injured ones. Of them, mesenchymal stem cells (MSCs) have long been considered a promising candidate for cell-based therapy due to their unspecialized, proliferative differentiation potential to specific cell lineage and, most importantly, their capacity of secreting beneficial paracrine factors which further promote neovascularization, angiogenesis, and cell survival. As a consequence, the differentiated MSCs could multiply and replace the damaged tissues to and turn into tissue- or organ-specific cells with specialized functions. These cells are also known to release potent anti-fibrotic factors including matrix metalloproteinases, which inhibit the proliferation of cardiac fibroblasts, thereby attenuating fibrosis. To achieve the highest possible therapeutic efficacy of stem cells, the other interventions, including hydrogels, electrical stimulations, or platelet-derived biomaterials, have been supplemented, which have resulted in a narrow to broad range of outcomes. Therefore, this article comprehensively analyzed the progress made in stem cells and combinatorial therapies to rescue infarcted myocardium.

scholarly journals Adipose-Derived Stem Cells: Current Applications and Future Directions in the Regeneration of Multiple Tissues

2020 ◽  
Vol 2020 ◽  
pp. 1-26
Author(s):  
Jiaxin Zhang ◽  
Yuzhe Liu ◽  
Yutong Chen ◽  
Lei Yuan ◽  
He Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Skin Wound ◽  
Current Status ◽  
Therapeutic Effects ◽  
Adipose Derived Stem Cells ◽  
Isolation And Identification ◽  
Comprehensive Overview ◽  
Skin Wound Healing ◽  
Paracrine Factors ◽  
Future Directions

Adipose-derived stem cells (ADSCs) can maintain self-renewal and enhanced multidifferentiation potential through the release of a variety of paracrine factors and extracellular vesicles, allowing them to repair damaged organs and tissues. Consequently, considerable attention has increasingly been paid to their application in tissue engineering and organ regeneration. Here, we provide a comprehensive overview of the current status of ADSC preparation, including harvesting, isolation, and identification. The advances in preclinical and clinical evidence-based ADSC therapy for bone, cartilage, myocardium, liver, and nervous system regeneration as well as skin wound healing are also summarized. Notably, the perspectives, potential challenges, and future directions for ADSC-related researches are discussed. We hope that this review can provide comprehensive and standardized guidelines for the safe and effective application of ADSCs to achieve predictable and desired therapeutic effects.

scholarly journals Comparison of Immunosuppressive and Angiogenic Properties of Human Amnion-Derived Mesenchymal Stem Cells between 2D and 3D Culture Systems

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Vitale Miceli ◽  
Mariangela Pampalone ◽  
Serena Vella ◽  
Anna Paola Carreca ◽  
Giandomenico Amico ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Three Dimensional ◽  
3D Culture ◽  
Culture Method ◽  
Paracrine Factors ◽  
Human Amnion ◽  
Tissue Repair And Regeneration ◽  
3D Culture System

The secretion of potential therapeutic factors by mesenchymal stem cells (MSCs) has aroused much interest given the benefits that it can bring in the field of regenerative medicine. Indeed, the in vitro multipotency of these cells and the secretive capacity of both angiogenic and immunomodulatory factors suggest a role in tissue repair and regeneration. However, during culture, MSCs rapidly lose the expression of key transcription factors associated with multipotency and self-renewal, as well as the ability to produce functional paracrine factors. In our study, we show that a three-dimensional (3D) culture method is effective to induce MSC spheroid formation, to maintain the multipotency and to improve the paracrine activity of a specific population of human amnion-derived MSCs (hAMSCs). The regenerative potential of both 3D culture-derived conditioned medium (3D CM) and their exosomes (EXO) was assessed against 2D culture products. In particular, tubulogenesis assays revealed increased capillary maturation in the presence of 3D CM compared with both 2D CM and 2D EXO. Furthermore, 3D CM had a greater effect on inhibition of PBMC proliferation than both 2D CM and 2D EXO. To support this data, hAMSC spheroids kept in our 3D culture system remained viable and multipotent and secreted considerable amounts of both angiogenic and immunosuppressive factors, which were detected at lower levels in 2D cultures. This work reveals the placenta as an important source of MSCs that can be used for eventual clinical applications as cell-free therapies.

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