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.

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.

Study of the effects of stromal vascular fraction, cultured adipose-derived stem cells, and paracrine factors of a conditioned medium in the treatment of severe radiation injuries of rat skin

2019 ◽  
pp. 24-32
Author(s):  
В.Г. Лебедев ◽  
Ю.Б. Дешевой ◽  
А.А. Темнов ◽  
Т.А. Астрелина ◽  
К.А. Рогов ◽  
...  
Keyword(s):  
Stem Cells ◽  
Adipose Tissue ◽  
Conditioned Medium ◽  
Stromal Vascular Fraction ◽  
Planar Geometry ◽  
X Rays ◽  
Radiation Injuries ◽  
Paracrine Factors ◽  
Wistar Kyoto ◽  
Radiation Ulcers

Цель - изучение влияния трансплантации стромально-васкулярной фракции (СВФ), культивированных мультипотентных мезенхимальных стволовых клеток (ММСК) жировой ткани и введения паракринных факторов кондиционной среды, полученных при культивировании ММСК, на течение тяжелых местных радиационных поражений кожи. Методика. Крыс инбредной линии Wistar-Kyoto облучали на рентгеновской установке в дозе 110 Гр, при мощности дозы 20,0 Гр/мин. Напряжение на трубке 30 кВ, ток 6,1 мА, фильтр Al толщиной 0,1 мм, площадь поля облучения составляла 8,5 см2. Трансплантацию клеток СВФ жировой ткани проводили двукратно в дозах 2,2 х 106 и 3,0 х 106 на 28-е и 35-е сут после облучения, соответственно. Культивированные ММСК вводили в дозах 2,8 × 106 и 3,4 × 106 на 28-е и 35-е сут после действия радиации. Паракринные факторы кондиционной среды вводили пятикратно с 1-х по 10-е сут после облучения, подкожно по 1,0 мл (общий белок 8 мг/мл). Тяжесть лучевого поражения кожи и эффекты терапии оценивали в динамике по клиническим проявлениям, с помощью планиметрии и патоморфологических методов. Результаты. Выбранный режим радиационного воздействия вызывал тяжелые лучевые поражения кожи с длительно (до 5 мес) незаживающими язвами. Площадь лучевых язв у крыс контрольной группы в период с 28-х до 84-х сут медленно уменьшалась от 2,73±0,17 см2 до 1,52±0,17 см2, а через 4 и 5 мес после облучения составляла 0,52±0,15 см2 и 0,05±0,04 см2, соответственно. Во всех опытных группах после 84-х сут отмечалась тенденция к снижению площади лучевых язв, а через 4 мес после облучения уменьшение площади язв и снижение тяжести поражения в опытных группах по сравнению с контролем были статистически значимыми (р < 0,05). У 70-80 % крыс в опытных группах через 4 мес после облучения наблюдалась полная эпителизация радиационных ран с образованием атрофического рубца, а в контрольной группе в этот период атрофические рубцы наблюдались лишь у 40% крыс. Заключение. Трансплантация СВФ жировой ткани или культивированных ММСК, а также введение паракринных факторов кондиционной среды способствуют усилению регенераторных процессов в пораженной ткани, и могут быть в равной степени эффективны при терапии тяжелых лучевых поражений кожи в эксперименте. Aim. To study effects of stromal-vascular fraction (SVF) transplantation, cultured multipotent mesenchymal stem cells (MMSC) of adipose tissue, and administration of paracrine factors of the conditioned MMSC culture medium on the course of severe, local radiation lesions of the skin. Methods. Wistar-Kyoto rats were irradiated with X-rays at a dose of 110 Gy and a dose rate of 20.0 Gy/min. The tube voltage was 30 kV, current - 6.1 mA, filter -0.1 mm thick A1, and irradiation field area - 8.5 cm2. Transplantation of adipose tissue SVF cells was performed twice at doses of 2.2 x 106 and 3.0 x 106 on the 28th and 35th days after irradiation, respectively. Cultured MMSC was administered at doses of 2.8 x 106 and 3,4 x 106 on the 28th and 35th days after irradiation. Paracrine factors of the conditioned medium were administered five times from the 1st to the 10th day after irradiation at a dose of 1.0 ml, s.c. (total protein, 8 mg/ml). Severity of radiation damage of the skin and effects of the therapy were followed up by clinical manifestations using planar geometry and pathomorphological methods. Results. Radiation exposure under the specified conditions caused severe radiation injuries of the skin with nonhealing ulcers that persisted for up to 5 months after irradiation. In control rats the area of radiation ulcers slowly decreased between the 28th and 84th days from 2.73 ± 0.17 cm2 to 1.52 ± 0.17 cm2, respectively, and was 0.52 ± 0.15 cm2 and 0.05 ± 0.04 cm2 at 4 and 5 months after irradiation. In all experimental groups, the healing was more intensive after the 84th day with a tendency to decrease the area of radiation ulcers; at 4 months after irradiation, statistically significant decreases in the area of ulcers and severity of lesions were observed in the experimental groups compared to the control (p <0.05). At four months after irradiation, 70-80% of rats in the treatment groups showed complete epithelialization of radiation wounds with formation of an atrophic scar whereas in the control group during the same period, atrophic scars were observed only in 40% of rats. Conclusion. Transplantation of adipose-derived SVF or cultured adipose tissue MMSC as well as administration of paracrine factors of the conditioned medium contributed to the enhancement of regenerative processes in the affected tissue and can be equally effective in the treatment of severe experimental radiation lesions of the skin.

Transplantion of autologous cells of stromal vascular fraction of adipose tissue in severe local radiation injuries of skin caused by x-ray

2017 ◽  
Vol 62 (1) ◽  
pp. 5-11 ◽  
Author(s):  
Бушманов ◽  
Andrey Bushmanov ◽  
Самойлов ◽  
Alyeksandr Samoylov ◽  
Добрынина ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Clinical Manifestations ◽  
Stromal Vascular Fraction ◽  
Control Group ◽  
Tissue Cell ◽  
X Rays ◽  
Radiation Injuries ◽  
X Ray ◽  
Local Radiation ◽  
Radiation Ulcers

Purpose: To investigate the effectiveness of autologous cells of stromal vascular fraction of adipose tissue in severe local radiation skin injuries after the exposure of rats to X-rays. Material and methods: Experiments were performed on Wistar rats, weighing 200–230 g. Rats were exposed locally in iliolumbar region using X-ray machine LNC-268 (RAP 100-10) at a dose of 110 Gy (30 kV tube voltage, current 6.1 mA, thick Al filter 0.1 mm), dose rate: 17.34 Gy/min. Area of the irradiation field was 8.2–8.5 cm2. Transplantation of autologous cells of stromal vascular fraction (SVFC) of adipose tissue was carried out on 21st or 35th days after irradiation. SVFC isolation was performed by means of enzymatic treatment of adipose tissue. SVFC suspension was administered subcutaneously at a dose of 1×106 cells per injection around the radiation ulcers.The severity of radiation damage to the skin and the effects of cellular therapy were evaluated in the dynamics of clinical manifestations, with the help of plane geometry and pathomorphometry. Results: It was found that by the 17–25th day after irradiation radiation ulcers were formedon rat skin. In the control group of animalsulcers persisted throughout the observation period of more than 3 months. The area of ulcers was 1,87 ± 0,35 cm2 and 1.52 ± 0.24 cm2 at 83th and 90th days after irradiation, respectively. In animals of the experimental group, with autologous stromal vascular fraction of adipose tissue, was significant decrease in ulceration the area in comparison to control animals. In 80 % of the rats treated with SVFC on 21st day after exposure, to the 90th day after irradiation complete healing of ulcers occurred with the formation of atrophic scar at the site of radiation injuries. These clinical observations and planimetric were correlated with the results of histomorphometry. Conclusion: Transplantation autologous SVFC of adipose tissue contributes to accelerate the healing of radiation ulcers after local x-ray exposure in the experiment, indicating that the prospects of using adipose tissue cell products for the treatment of severe local radiation injuries.

scholarly journals Evaluation of the Effectiveness of Mesenchymal Stem Cells of the Placenta and Their Conditioned Medium in Local Radiation Injuries

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2558
Author(s):  
Vitaliy Brunchukov ◽  
Tatiana Astrelina ◽  
Daria Usupzhanova ◽  
Anna Rastorgueva ◽  
Irina Kobzeva ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Complete Healing ◽  
Laboratory Animals ◽  
Control Group ◽  
Radiation Injuries ◽  
Wound Surface ◽  
Open Wound ◽  
Local Radiation

Background: The search for an effective therapy for local radiation injuries (LRI) is urgent; one option is mesenchymal stem cells (MSC) derived from the placenta and their conditioned medium for the regenerative processes of the skin. Methods: We used 80 animals, randomly assigned to four groups: control (C) animals that did not receive therapy; control with the introduction of culture medium concentrate (CM); introduction of MSCs (PL); introduction of CMPL. LRI modeling was performed on an X-ray machine at a dose of 110 Gy. Histological and immunohistochemical tests were performed. Results: On the 112th day, the area of the open wound surface in the CMPL group was 6.7 times less than in the control group. Complete healing of the open wound surface of the skin in the CM group was observed in 40%, in CMPL 60%, in the PL group 20%, and in the C group there were no animals with a prolonged wound defect. A decrease in inflammatory processes was observed in the CMPL group. Conclusions: the use of a concentrate of conditioned MSCs (CMPL group) in severe LRI in laboratory animals accelerates the transition of the wound process to the stage of regeneration and epithelization.

Comparison of the therapeutic potential of human and rats mesenchymal stem cells and their conditioned medium with local radiation injuries

Cytotherapy ◽  
2021 ◽  
Vol 23 (5) ◽  
pp. S44
Author(s):  
T. Astrelina ◽  
V. Brunchukov ◽  
A. Rastorgueva ◽  
D. Usupzhanova ◽  
V. Nikitina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Therapeutic Potential ◽  
Radiation Injuries ◽  
Local Radiation

scholarly journals The Compromised Anti-microbial Function of Mesenchymal Stem Cells in Diabetic Patients

2017 ◽  
Vol 2 (3) ◽  
pp. 2473011417S0004
Author(s):  
Zijun Zhang ◽  
Lew Schon ◽  
Young Cho
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bacterial Infection ◽  
Conditioned Medium ◽  
Culture Media ◽  
Cell Metabolism ◽  
Diabetic Group ◽  
Diabetic Patients ◽  
Paracrine Factors ◽  
E Coli

Category: Basic Sciences/Biologics Introduction/Purpose: Diabetic foot infection (DFI), including skin infection and osteomyelitis, is a severe complication of late- stage diabetes. Mesenchymal stem cells (MSCs) facilitate bacterial clearance. In bacterial infection, MSCs, via paracrine mediators, regulate the host cell metabolism and inflammatory response. Particularly, MSCs augment the antibacterial function of neutrophils. It is generally believed that hyperglycemia in diabetes is toxic to MSCs/progenitors and detrimental to their regenerative function. It is unknown, however, whether the antibacterial function of MSCs is compromised in diabetes. Methods: Bone marrow samples from 6 diabetic and 4 non-diabetic patients (approved by IRB) were used for MSC isolation. 1. MSCs from both diabetic and non-diabetic patients were treated with lipopolysaccharides (LPS), a bacterial wall component, for 6 hours. The tissue culture media were collected as conditioned medium. E. coli from a single colony were cultured with addition of the conditioned medium generated by either diabetic or non-diabetic MSCs and inoculated on LB-agar plates overnight. Bacterial colonies were counted. 2. Human macrophages were isolated from umbilical cord blood and co-cultured with either diabetic or non-diabetic MSCs, in a trans-well system, for 24 hours. The macrophages were then cultured with heat-inactivated E. coli for one hour. After extensive washing, macrophage and bacteria were stained with Pappenheim method. Bacterial phagocytosis of macrophages, after co- cultured with diabetic or non-diabetic MSCs, was assessed under a microscope. Results: There was no statistical difference in the number of E. coli colonies when regular medium produced by diabetic and non- diabetic MSCs was added into the bacterial culture. When the diabetic and non-diabetic MSCs were treated with LPS and the conditioned medium was collected and added into bacterial cultures, E. coli colonies increased in the diabetic group, about 3 fold, as compared with the non-diabetic group (p < 0.05). Macrophages were counted in defined areas of the Petri dishes and designated as infected or uninfected, according to the presentation of bacterial bodies or not. While the infection rate of macrophages co-cultured with non-diabetic MSCs was 85% (±5.5%), it was 70% (±6.6%) when macrophages were co-cultured with diabetic MSCs (p = 0.006). Conclusion: MSCs-produced paracrine factors suppressed the growth of E. coli but diabetic and non-diabetic MSCs had no difference in such a function. Activation with LPS did not augment the non-diabetic MSCs but weakened diabetic MSCs in suppression of bacterial growth. MSCs regulate macrophages in bacterial phagocytosis. Diabetic MSCs, however, had a limited role in regulation of macrophages. This study demonstrated that MSCs in diabetic patients are compromised in anti-bacterial infection. The results not only deepen the understanding of bacterial infection in diabetes but also open up new strategy to control bacterial infection in diabetic patients.

scholarly journals Adipose tissue-derived mesenchymal stem cells have better restorative capacity than bone marrow-derived cells in a cerebellar ataxic rat model

2020 ◽  
Author(s):  
Rasha Att ◽  
Angie Ameen ◽  
Horeya Korayem ◽  
Noha Abogresha ◽  
Yasser El-Wazir
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Motor Performance ◽  
Therapeutic Potential ◽  
Monosodium Glutamate ◽  
Control Group

IntroductionRegenerative treatment using stem cells represents a potentially effective therapy for cerebellar ataxia (CA). We compared the therapeutic potential of adipose tissue stem cells (ASCs) and bone marrow mesenchymal stem cells (BM-MSCs) in a rodent monosodium glutamate (MSG)-induced CA cell (BM-MSC) model.Material and methodsFemale Wistar rats (n = 40) were equally divided into a saline-treated control group and 3 MSG-induced CA groups randomly treated with either saline, or 1 × 106 ASCs or BM-MSCs. We assessed the following: 1) cerebellar motor functions in vivo (by Rotarod test, open-field test, and Quantitative gait analysis); 2) cerebellar histological architecture; and 3) cerebellar immunohistochemical examination of the Bax/Bcl-2 ratio as in indicator of apoptosis, and the levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) as neuroprotective factors.ResultsTreatment with either of the MSCs improved MSG-induced poor motor performance, restored the disrupted Purkinje cell layer, decreased neuronal apoptosis and enhanced cerebellar VEGF and IGF-1 levels observed in CA rats. Adipose tissue stem cells showed superiority over BM-MSCs in the improvement of some motor performance parameters and cerebellar VEGF and IGF-1 levels.ConclusionsIn conclusion, both stem cell types induced structural, physiological, and biochemical improvement, with ASCs being best for treatment of CA.

scholarly journals APPLICATION OF CELLULAR TECHNOLOGIES FOR REGENERATION OF PERIODONTAL TISSUES IN EXPERIMENT

2018 ◽  
Vol 62 (4) ◽  
pp. 463-472 ◽  
Author(s):  
Sergei P. Rubnikovich ◽  
Igor D. Volotovsky ◽  
Yulia L. Denisova ◽  
Тatiana E. Vladimirskaya ◽  
Vasilina A. Andreeva ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
Morphological Changes ◽  
Fibrous Tissue ◽  
Laboratory Animals ◽  
Control Group ◽  
Cell Transplant ◽  
Periodontal Tissues ◽  
White Rats

A promising scope of modern scientific research is the use of autologous and allogeneic mesenchymal stem cells for regeneration of periodontal tissues. The aim of the study was to evaluate the nature of morphological changes in the pathologically altered periodontal tissues after injection of a biotransplant containing mesenchymal stem cells of the adipose tissue immobilized on a collagen carrier in an animal experiment. In the experiment, 60 randobbred females of white rats were used as a model, whose adipose tissue was taken to obtain allogenic mesenchymal stem cells. All animals were divided into 5 groups, depending on the planned method of treatment – 10 rats each. The control group consisted of 10 laboratory animals with healthy gingiva. The experimental gingival recession model was created by the V-shaped excision of periodontal tissues. The bioplastic collagen material “Collost” gel 7 % in isolated form determines the fibrosis intensification and serves as a “matrix” for the formation of a fibrous tissue, ensures the adhesion of stem cells and their transformation into pro- and fibroblasts. Injection of a cell transplant suspension into physiological saline activates the processes of cell proliferation and transformation of fibroblast differentiating cells. Suspension of the cell transplant on a sterile bioplastic collagen material “Collost” gel 7 % enhances the effects of gel and stem cells, promotes the leveling of atrophic and dystrophic changes in the gum, strengthening a mechanical component, reducing the recession of the gum and the depth of the gingival pocket.

scholarly journals S100A8/A9 Enhances Immunomodulatory and Tissue-Repairing Properties of Human Amniotic Mesenchymal Stem Cells in Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 22 (20) ◽  
pp. 11175
Author(s):  
Tzu-Jou Chen ◽  
Yen-Ting Yeh ◽  
Fu-Shiang Peng ◽  
Ai-Hsien Li ◽  
Shinn-Chih Wu
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myocardial Ischemia ◽  
Conditioned Medium ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Amniotic Mesenchymal Stem Cells ◽  
Myocardial Ischemia Reperfusion

Paracrine factors of human mesenchymal stem cells (hMSCs) have the potential of preventing adverse cardiac remodeling after myocardial infarction (MI). S100A8 and S100A9 are calcium-binding proteins playing essential roles in the regulation of inflammation and fibrous tissue formation, and they might modulate the paracrine effect of hMSCs. We isolated human amniotic mesenchymal stem cells (hAMSCs) and examined the changes in the expression level of regulatory genes of inflammation and fibrosis after hAMSCs were treated with S100A8/A9. The anti-inflammatory and anti-fibrotic effects of hAMSCs pretreated with S100A8/A9 were shown to be superior to those of hAMSCs without S100A8/A9 pretreatment in the cardiomyocyte hypoxia/reoxygenation experiment. We established a murine myocardial ischemia/reperfusion model to compare the therapeutic effects of the conditioned medium of hAMSCs with or without S100A8/A9 pretreatment. We found the hearts administered with a conditioned medium of hAMSCs with S100A8/A9 pretreatment had better left ventricular systolic function on day 7, 14, and 28 after MI. These results suggest S100A8/A9 enhances the paracrine therapeutic effects of hAMSCs in aspects of anti-inflammation, anti-fibrosis, and cardiac function preservation after MI.

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