Pub Date : 2022-07-06DOI: 10.3390/transplantology3030024
R. Hage, M. Schuurmans
COVID-19 can be associated with lung fibrosis. Although lung fibrosis after COVID-19 is a relatively rare finding, the mere fact that globally a very large number of patients have had COVID-19 leads to a significant burden of disease. However, patients with COVID-19-associated lung fibrosis have different clinical and radiological features. The aim of this review is to define the different phenotypes of COVID-19-associated lung fibrosis, based on the medical literature. We found that two phenotypes have emerged. One phenotype is COVID-19-related acute respiratory distress syndrome (CARDS); the other phenotype is post-COVID-19 pulmonary fibrosis (PCPF). Both phenotypes have different risk factors, clinical, and radiological features, and differ in their pathophysiological mechanisms and prognoses. A long-term follow-up of patients with pulmonary complications after COVID-19 is warranted, even in patients with only discrete fibrosis. Further studies are needed to determine the optimal treatment because currently the literature is scarce, and evidence is only based on small case series or case reports.
{"title":"COVID-19-Associated Lung Fibrosis: Two Pathways and Two Phenotypes, Lung Transplantation, and Antifibrotics","authors":"R. Hage, M. Schuurmans","doi":"10.3390/transplantology3030024","DOIUrl":"https://doi.org/10.3390/transplantology3030024","url":null,"abstract":"COVID-19 can be associated with lung fibrosis. Although lung fibrosis after COVID-19 is a relatively rare finding, the mere fact that globally a very large number of patients have had COVID-19 leads to a significant burden of disease. However, patients with COVID-19-associated lung fibrosis have different clinical and radiological features. The aim of this review is to define the different phenotypes of COVID-19-associated lung fibrosis, based on the medical literature. We found that two phenotypes have emerged. One phenotype is COVID-19-related acute respiratory distress syndrome (CARDS); the other phenotype is post-COVID-19 pulmonary fibrosis (PCPF). Both phenotypes have different risk factors, clinical, and radiological features, and differ in their pathophysiological mechanisms and prognoses. A long-term follow-up of patients with pulmonary complications after COVID-19 is warranted, even in patients with only discrete fibrosis. Further studies are needed to determine the optimal treatment because currently the literature is scarce, and evidence is only based on small case series or case reports.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82396147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-30DOI: 10.3390/transplantology3030023
M. Salvadori, A. Tsalouchos
Multiple case series of kidney transplant recipients with COVID-19 have shown increased mortality compared to nontransplant patients. To date, we do not have high-level evidence to inform immunosuppression minimization strategies in infected transplant recipients. Most centers, however, have adopted an early antimetabolite withdrawal in addition to other interventions. The epidemiological problem concerns also dialysis patients and waitlisted patients who have a higher COVID-19 infection diffusion with respect to kidney transplant recipients. Several factors influence mortality among kidney transplant recipients. Among these factors are the age, race, and comorbidity factors, such as hypertension, diabetes mellitus, obesity, and previous respiratory problems. Treatment is still limited. The only effective antiviral drug is remdesivir that should be administered before the development of the cytokine storm. Vaccination seems to be useful, but due to the concomitant immunosuppression limiting its efficacy, at least three or four doses should be administered.
{"title":"COVID-19 and Kidney Transplantation: Epidemiology, Histopathological Presentation, Clinical Presentation and Outcomes, and Therapeutic Strategies","authors":"M. Salvadori, A. Tsalouchos","doi":"10.3390/transplantology3030023","DOIUrl":"https://doi.org/10.3390/transplantology3030023","url":null,"abstract":"Multiple case series of kidney transplant recipients with COVID-19 have shown increased mortality compared to nontransplant patients. To date, we do not have high-level evidence to inform immunosuppression minimization strategies in infected transplant recipients. Most centers, however, have adopted an early antimetabolite withdrawal in addition to other interventions. The epidemiological problem concerns also dialysis patients and waitlisted patients who have a higher COVID-19 infection diffusion with respect to kidney transplant recipients. Several factors influence mortality among kidney transplant recipients. Among these factors are the age, race, and comorbidity factors, such as hypertension, diabetes mellitus, obesity, and previous respiratory problems. Treatment is still limited. The only effective antiviral drug is remdesivir that should be administered before the development of the cytokine storm. Vaccination seems to be useful, but due to the concomitant immunosuppression limiting its efficacy, at least three or four doses should be administered.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90904753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-16DOI: 10.3390/transplantology3020021
H. Hardgrave, Allison Wells, J. Nigh, T. Osborn, Garrett N. Klutts, Derek Krinock, M. Rude, Sushma Bhusal, L. Burdine, E. Giorgakis
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was declared a pandemic in March 2020. Its reported impact on solid-organ-transplant-recipient morbidity and mortality has varied. The aim of this study was to present the effect of transplant status, patient comorbidities and immunosuppression modality on the survival of solid-organ-transplant recipients who contracted SAR-CoV-2 during the pre-vaccination era, at a single academic transplant center. Patients (n = 103) were assessed for 90-day mortality. A univariate analysis identified an age of over 60 years (HR = 10, p = 0.0034), Belatacept (HR = 6.1, p = 0.022), and Cyclosporine (HR = 6.1, p = 0.0089) as significant mortality risk factors; Tacrolimus was protective (HR = 0.23, p = 0.022). Common metabolic comorbidities (hypertension, diabetes, obesity) did not stand out as risk factors in our patient cohort. This study on the unvaccinated is expected to facilitate a paired comparison of outcomes in transplanted patients who contracted SARS-CoV-2 during the latter period of the pandemic, when broad SARS-CoV-2 vaccination and novel antibody treatments became broadly available.
2020年3月，严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2)被宣布为大流行。据报道，其对实体器官移植受体发病率和死亡率的影响各不相同。本研究的目的是在单个学术移植中心研究移植状态、患者合并症和免疫抑制方式对接种前感染sars - cov -2的实体器官移植受者生存的影响。对103例患者进行90天死亡率评估。单因素分析发现，年龄超过60岁(HR = 10, p = 0.0034)、Belatacept (HR = 6.1, p = 0.022)和环孢素(HR = 6.1, p = 0.0089)是显著的死亡危险因素;他克莫司具有保护作用(HR = 0.23, p = 0.022)。在我们的患者队列中，常见的代谢合并症(高血压、糖尿病、肥胖)没有作为危险因素出现。这项针对未接种疫苗患者的研究预计将有助于对在大流行后期感染SARS-CoV-2的移植患者的结果进行配对比较，当时广泛的SARS-CoV-2疫苗接种和新型抗体治疗已广泛可用。
{"title":"SARS-CoV-2 Infection of Unvaccinated Liver- and Kidney-Transplant Recipients: A Single-Center Experience of 103 Consecutive Cases","authors":"H. Hardgrave, Allison Wells, J. Nigh, T. Osborn, Garrett N. Klutts, Derek Krinock, M. Rude, Sushma Bhusal, L. Burdine, E. Giorgakis","doi":"10.3390/transplantology3020021","DOIUrl":"https://doi.org/10.3390/transplantology3020021","url":null,"abstract":"Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was declared a pandemic in March 2020. Its reported impact on solid-organ-transplant-recipient morbidity and mortality has varied. The aim of this study was to present the effect of transplant status, patient comorbidities and immunosuppression modality on the survival of solid-organ-transplant recipients who contracted SAR-CoV-2 during the pre-vaccination era, at a single academic transplant center. Patients (n = 103) were assessed for 90-day mortality. A univariate analysis identified an age of over 60 years (HR = 10, p = 0.0034), Belatacept (HR = 6.1, p = 0.022), and Cyclosporine (HR = 6.1, p = 0.0089) as significant mortality risk factors; Tacrolimus was protective (HR = 0.23, p = 0.022). Common metabolic comorbidities (hypertension, diabetes, obesity) did not stand out as risk factors in our patient cohort. This study on the unvaccinated is expected to facilitate a paired comparison of outcomes in transplanted patients who contracted SARS-CoV-2 during the latter period of the pandemic, when broad SARS-CoV-2 vaccination and novel antibody treatments became broadly available.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77888082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Spinal cord injuries (SCI) lead to large-scale physical, physiological, psychological and professional losses. Therefore, today, one of the urgent aims of neurophysiology is the study of the consequences of spinal cord injury. The most common type of SCI is a hemisection. For a comprehensive and detailed study of the functional post-traumatic recovery of the spinal cord, various hemisection options are developed. The aim of the study was to analyse the level of locomotor activity and changes in spasticity of the mice ipsilateral hindlimb (IH) after SCI. Materials and methods. The injury of the left-side spinal cord hemisection was modelled at the level of the lower thoracic segments (T10-T11) in female FVB mice. The locomotor activity and spasticity of the IH were determined every week using the Basso-Beattie-Bresnahan (ВВВ), the Basso (B) scales and the Ashworth scale during the first 1-12 weeks of the post-traumatic period. Results. At a later date (the 11th, 12th weeks) compared with the first weeks of the post-traumatic period, there was a marked recovery of the IH function: 4.39±0.61 points (out of 21 possible) on the BBB scale and 2.22±0.31 points (out of 9 possible) on the B scale. However, at all studied time interval after SCI, a consistently high level of hindlimb spasticity in experimental animals was noted, on the 12th week: 3.03±0.39 (out of 4 possible) on the Ashworth scale. Conclusions. After modelling spinal cord injury by hemisection, spontaneous post-traumatic recovery of locomotor activity was observed (since the 2nd week), which had scores corresponding to the early recovery phase. On the other hand, the levels of IH spasticity in mice were quite high throughout the entire study period, although already at the 2nd week there was a slight decrease in this parameter compared to the 1st week of the post-traumatic period.
{"title":"Locomotor activity and spasticity level of the limb in female mice with a spinal cord injury model","authors":"Yu. R. Nesterenko, O. Rybachuk","doi":"10.22494/cot.v10i1.136","DOIUrl":"https://doi.org/10.22494/cot.v10i1.136","url":null,"abstract":"Spinal cord injuries (SCI) lead to large-scale physical, physiological, psychological and professional losses. Therefore, today, one of the urgent aims of neurophysiology is the study of the consequences of spinal cord injury. The most common type of SCI is a hemisection. For a comprehensive and detailed study of the functional post-traumatic recovery of the spinal cord, various hemisection options are developed. The aim of the study was to analyse the level of locomotor activity and changes in spasticity of the mice ipsilateral hindlimb (IH) after SCI. Materials and methods. The injury of the left-side spinal cord hemisection was modelled at the level of the lower thoracic segments (T10-T11) in female FVB mice. The locomotor activity and spasticity of the IH were determined every week using the Basso-Beattie-Bresnahan (ВВВ), the Basso (B) scales and the Ashworth scale during the first 1-12 weeks of the post-traumatic period. Results. At a later date (the 11th, 12th weeks) compared with the first weeks of the post-traumatic period, there was a marked recovery of the IH function: 4.39±0.61 points (out of 21 possible) on the BBB scale and 2.22±0.31 points (out of 9 possible) on the B scale. However, at all studied time interval after SCI, a consistently high level of hindlimb spasticity in experimental animals was noted, on the 12th week: 3.03±0.39 (out of 4 possible) on the Ashworth scale. Conclusions. After modelling spinal cord injury by hemisection, spontaneous post-traumatic recovery of locomotor activity was observed (since the 2nd week), which had scores corresponding to the early recovery phase. On the other hand, the levels of IH spasticity in mice were quite high throughout the entire study period, although already at the 2nd week there was a slight decrease in this parameter compared to the 1st week of the post-traumatic period.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47547327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Uzlenkova, N. Skorobogatova, A. Kryvko, M. Krasnoselsky
At present, applying multipotent mesenchymal stromal cells (MSCs) as cell therapy for radiation damages have gained increasing attention since current medical management remains far from satisfactory. The aim of the study is to examine the efficacy of cryopreserved ex vivo expanded bone marrow-derived MSCs (rBM-MSCs) to the repair of radiation injuries on rat models of total and local radiation exposure. Materials and methods. The MSCs were derived from bone marrow of non-irradiated female albino rats aged 4 months, short-term ex vivo expanded for two passages and cryopreserved under dimethyl sulfoxide cryoprotection for low temperature storage at -70 oC for 6-12 months. The cryopreserved samples from each batch of rBM-MSCs culture were tested for the viability and functional characteristics before being transplanted to rats in experiments in vivo. The acute radiation damages in rats were modeled by total body irradiation (TBI) at doses of 5.5 Gy (TBI 5.5) and 7.0 Gy (TBI 7.0) and locally irradiated in the right hip skin at a dose of 50 Gy. The cryopreserved rBM-MSCs (1.5•106 and 0.5•106 cells/animal) were intravenously transplanted within 24 h following TBI and locally injected (twice 1.5•106 Cells/animals) on days 15 and 21 following thigh irradiation. The efficacy of cryopreserved rBM-MSCs was assessed by survival and hematological study as well as the irradiated skin wound healing assay. Results. The cryopreserved ex vivo expanded rBM-MSCs were characterized by high level of functional activity with cell viability about 80 %, include at least 8.5 % of the colony forming MSCs and MSCs with ability to adipogenic and osteogenic differentiation In TBI 5.5 rats, cryopreserved transplanted rBM-MSCs (1.5·106 cells/animal) prevented acute leukopenia in the first critical days of the radiation injury by increasing the number of leukocytes by 3.7 times on day 2 and contributed to a more complete recovery of hematological disorders by increasing the BM cells number and platelet count on day 22, which led to the increase of the increase of overall survival up to 100 % with a regain of body weight. In TBI 7.0 rats, the lower transplanted dose of rBM-MSCs (0.5•106 cells/animal) was more effective in terms of general recovery and extended the overall survival time for 6 days. The locally injected rBM-MSCs (twice 1.5•106 cells/animals) reduced the severity and promoted the healing of radiation skin wounds according to the results of scoring and wound size assay. Conclusion. The present study confirms that the cryopreserved ex vivo expanded rBM-MSCs were functionally complete for the therapeutic use on rat models of experimental radiation damage and were effective for the recovery of hematopoietic system and severe skin wound after radiation exposure.
{"title":"The efficacy of cryopreserved ex vivo expanded rat bone marrow-derived multipotent mesenchymal stromal cells in the repair of radiation injuries in rats","authors":"N. Uzlenkova, N. Skorobogatova, A. Kryvko, M. Krasnoselsky","doi":"10.22494/cot.v10i1.139","DOIUrl":"https://doi.org/10.22494/cot.v10i1.139","url":null,"abstract":"At present, applying multipotent mesenchymal stromal cells (MSCs) as cell therapy for radiation damages have gained increasing attention since current medical management remains far from satisfactory. The aim of the study is to examine the efficacy of cryopreserved ex vivo expanded bone marrow-derived MSCs (rBM-MSCs) to the repair of radiation injuries on rat models of total and local radiation exposure. Materials and methods. The MSCs were derived from bone marrow of non-irradiated female albino rats aged 4 months, short-term ex vivo expanded for two passages and cryopreserved under dimethyl sulfoxide cryoprotection for low temperature storage at -70 oC for 6-12 months. The cryopreserved samples from each batch of rBM-MSCs culture were tested for the viability and functional characteristics before being transplanted to rats in experiments in vivo. The acute radiation damages in rats were modeled by total body irradiation (TBI) at doses of 5.5 Gy (TBI 5.5) and 7.0 Gy (TBI 7.0) and locally irradiated in the right hip skin at a dose of 50 Gy. The cryopreserved rBM-MSCs (1.5•106 and 0.5•106 cells/animal) were intravenously transplanted within 24 h following TBI and locally injected (twice 1.5•106 Cells/animals) on days 15 and 21 following thigh irradiation. The efficacy of cryopreserved rBM-MSCs was assessed by survival and hematological study as well as the irradiated skin wound healing assay. Results. The cryopreserved ex vivo expanded rBM-MSCs were characterized by high level of functional activity with cell viability about 80 %, include at least 8.5 % of the colony forming MSCs and MSCs with ability to adipogenic and osteogenic differentiation In TBI 5.5 rats, cryopreserved transplanted rBM-MSCs (1.5·106 cells/animal) prevented acute leukopenia in the first critical days of the radiation injury by increasing the number of leukocytes by 3.7 times on day 2 and contributed to a more complete recovery of hematological disorders by increasing the BM cells number and platelet count on day 22, which led to the increase of the increase of overall survival up to 100 % with a regain of body weight. In TBI 7.0 rats, the lower transplanted dose of rBM-MSCs (0.5•106 cells/animal) was more effective in terms of general recovery and extended the overall survival time for 6 days. The locally injected rBM-MSCs (twice 1.5•106 cells/animals) reduced the severity and promoted the healing of radiation skin wounds according to the results of scoring and wound size assay. Conclusion. The present study confirms that the cryopreserved ex vivo expanded rBM-MSCs were functionally complete for the therapeutic use on rat models of experimental radiation damage and were effective for the recovery of hematopoietic system and severe skin wound after radiation exposure.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48600997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is known that a deficiency of estrogens of any origin (physiological menopause, surgical removal of the ovaries, etc.) accelerates the aging processes of both the body in general and the skin in particular in women. Studies of the morphometric properties of skin caused by estrogen-deficient states may help in the development of more effective regenerative medicine approaches aimed at treating and preventing age-related skin changes. The purpose of the study is to determine the morphological changes in the skin of young and old SBA/Сa mice with estrogen deficiency on the ovariectomy model. Materials and methods. Skin samples from young (4 months) and old (16 months) mice two months after ovariectomy were compared with age-matched sham-operated mice. The thickness of the epidermis and dermis, the number of hair follicles, and sebaceous glands were determined on histological samples of the skin. Results and discussion. It was shown that the thickness of the epidermis was significantly smaller both in the group of young and in the group of old ovariectomized mice compared to the thickness of the epidermis of the control group of animals of the corresponding age. A significant increase in the thickness of the dermis was found in the group of young ovariectomized mice in comparison with the thickness of the dermis in the young control group, however, in the group of old ovariectomized mice, the thickness of the dermis did not differ significantly compared to the age-matched control group. No significant differences were found in the number of sebaceous glands and hair follicles in the studied groups. Conclusions. Ovariectomy, as a model of artificial estrogen deficiency, is accompanied by significant changes in the epidermis in young and old animals and the dermis in young ovariectomized animals, without affecting the number of sebaceous glands and hair follicles.
{"title":"Morphometric analysis of skin in ovariectomized mice of different ages","authors":"V. Ivanishchev, A. Ustymenko, G. Butenko","doi":"10.22494/cot.v10i1.138","DOIUrl":"https://doi.org/10.22494/cot.v10i1.138","url":null,"abstract":"It is known that a deficiency of estrogens of any origin (physiological menopause, surgical removal of the ovaries, etc.) accelerates the aging processes of both the body in general and the skin in particular in women. Studies of the morphometric properties of skin caused by estrogen-deficient states may help in the development of more effective regenerative medicine approaches aimed at treating and preventing age-related skin changes. The purpose of the study is to determine the morphological changes in the skin of young and old SBA/Сa mice with estrogen deficiency on the ovariectomy model. Materials and methods. Skin samples from young (4 months) and old (16 months) mice two months after ovariectomy were compared with age-matched sham-operated mice. The thickness of the epidermis and dermis, the number of hair follicles, and sebaceous glands were determined on histological samples of the skin. Results and discussion. It was shown that the thickness of the epidermis was significantly smaller both in the group of young and in the group of old ovariectomized mice compared to the thickness of the epidermis of the control group of animals of the corresponding age. A significant increase in the thickness of the dermis was found in the group of young ovariectomized mice in comparison with the thickness of the dermis in the young control group, however, in the group of old ovariectomized mice, the thickness of the dermis did not differ significantly compared to the age-matched control group. No significant differences were found in the number of sebaceous glands and hair follicles in the studied groups. Conclusions. Ovariectomy, as a model of artificial estrogen deficiency, is accompanied by significant changes in the epidermis in young and old animals and the dermis in young ovariectomized animals, without affecting the number of sebaceous glands and hair follicles.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42774056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In modern regenerative medicine, the use of adipose-derived multipotent mesenchymal stromal cells (ADSCs) is an important strategy for the treatment of many diseases, including age-dependent ones. However, the question of a direct link between the aging of ADSCs and the aging of the body as a whole remains open. The purpose of the study was to determine the morphofunctional properties of multipotent mesenchymal stromal cells of adipose tissue in young and old mice when cultured in vitro. Materials and methods. Subcutaneous adipose tissue was isolated from young (2 months old) and old (14 months old) female CBA/Ca mice, fermented, and the stromal vascular fraction was obtained. ADSCs were isolated after cell culturing for 2nd passage. Cells were phenotyped by flow cytometry and morphological characteristics, proliferative potential, ability to directed multilinear differentiation in osteogenic, adipogenic directions were evaluated in vitro. Results. ADSCs obtained from old animals after the second passage showed a decrease in the proliferative, clonogenic potentials of ADSCs in vitro compared to the cells from young animals. In addition, the osteogenic potential of ADSCs in vitro decreased and the potential for adipogenic differentiation increased. Conclusions. The results of the study indicate an age-dependent effect on the functional activity of ADSCs, which is manifested by a disorder of their potential for proliferation, colony formation and directed differentiation.
{"title":"Morphofunctional characteristics of adipose-derived multipotent mesenchymal stromal cells from CBA/Ca mice of different ages in cell culture in vitro","authors":"A. Ustymenko, Vitalii Kyryk, G. Butenko","doi":"10.22494/cot.v10i1.137","DOIUrl":"https://doi.org/10.22494/cot.v10i1.137","url":null,"abstract":"In modern regenerative medicine, the use of adipose-derived multipotent mesenchymal stromal cells (ADSCs) is an important strategy for the treatment of many diseases, including age-dependent ones. However, the question of a direct link between the aging of ADSCs and the aging of the body as a whole remains open. The purpose of the study was to determine the morphofunctional properties of multipotent mesenchymal stromal cells of adipose tissue in young and old mice when cultured in vitro. Materials and methods. Subcutaneous adipose tissue was isolated from young (2 months old) and old (14 months old) female CBA/Ca mice, fermented, and the stromal vascular fraction was obtained. ADSCs were isolated after cell culturing for 2nd passage. Cells were phenotyped by flow cytometry and morphological characteristics, proliferative potential, ability to directed multilinear differentiation in osteogenic, adipogenic directions were evaluated in vitro. Results. ADSCs obtained from old animals after the second passage showed a decrease in the proliferative, clonogenic potentials of ADSCs in vitro compared to the cells from young animals. In addition, the osteogenic potential of ADSCs in vitro decreased and the potential for adipogenic differentiation increased. Conclusions. The results of the study indicate an age-dependent effect on the functional activity of ADSCs, which is manifested by a disorder of their potential for proliferation, colony formation and directed differentiation.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44588222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
I. Labunets, N. Utko, T. Panteleymonova, Vitalii Kyryk, Y. Kharkevych, A. Rodnichenko, Z. Litoshenko, G. Butenko
The transplantation of adipose-derived multipotent mesenchymal stromal cells (ADSCs) in Parkinson’s disease/parkinsonism is a promising area in their therapy. The effects of such cells may be influenced by the age of the donor and biologically active factors. The purpose of the study is to compare the effect of transplanted ADSCs of donor mice of different age on the parameters of behaviour, oxidative stress and neuroinflammation in the brain of mice with an experimental model of parkinsonism; to evaluate changes in the effects of cells from older donors under the influence of exogenous hormone melatonin. Materials and methods. The object of the study was adult (5-6 months) and aging (15-17 months) 129/Sv mice. Adult mice were injected once with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and after 17 days – ADSCs of adult or aging donor mice at a dose of 700 thousand cells in the tail vein. Some mice received ADSCs of aging donors in combination with melatonin. Behavioural parameters were assessed in open-field, rigidity and rotarod tests; the relative content of macrophages was measured in the brain, malondialdehyde (MDA), the activity of antioxidant enzymes. Results. Under the influence of MPTP, the number of squares, rearings, body length and length is significantly less than in the intact group, and muscle tone is higher; in the brain the content of MDA and macrophages increases and the activity of superoxide dismutase (SOD) decreases. After the transplantation of adult donor ADSCs, the parameters of body and step length increase significantly, but not to the level of intact mice; the activity of SOD, glutathione reductase (GR) and the proportion of macrophages increase in the brain. After the administration of ADSCs of aging donors, the values of behavioural parameters and the proportion of macrophages in the brain correspond to the control group (only MPTP), and the activity of SOD corresponds to intact animals. In mice treated with ADSCs of aging donors in combination with melatonin, the direction of changes in behavioural parameters, SOD and GR activity, macrophage percentage was similar to that observed after the administration of adult donor ADSCs. Conclusions. The effects of ADSCs transplantation in mice with the MPTP model of parkinsonism depend on the age of the donor and are more pronounced in transplanted cells derived from adult mice. The effects of ADSCs from aging donors in combination with melatonin are consistent with those observed after administration of cells from adult donors.
{"title":"The effects of transplanted adipose-derived multipotent mesenchymal stromal cells from mice of different age or from aging donors in combination with melatonin at experimental parkinsonism","authors":"I. Labunets, N. Utko, T. Panteleymonova, Vitalii Kyryk, Y. Kharkevych, A. Rodnichenko, Z. Litoshenko, G. Butenko","doi":"10.22494/cot.v10i1.134","DOIUrl":"https://doi.org/10.22494/cot.v10i1.134","url":null,"abstract":"The transplantation of adipose-derived multipotent mesenchymal stromal cells (ADSCs) in Parkinson’s disease/parkinsonism is a promising area in their therapy. The effects of such cells may be influenced by the age of the donor and biologically active factors. The purpose of the study is to compare the effect of transplanted ADSCs of donor mice of different age on the parameters of behaviour, oxidative stress and neuroinflammation in the brain of mice with an experimental model of parkinsonism; to evaluate changes in the effects of cells from older donors under the influence of exogenous hormone melatonin. Materials and methods. The object of the study was adult (5-6 months) and aging (15-17 months) 129/Sv mice. Adult mice were injected once with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and after 17 days – ADSCs of adult or aging donor mice at a dose of 700 thousand cells in the tail vein. Some mice received ADSCs of aging donors in combination with melatonin. Behavioural parameters were assessed in open-field, rigidity and rotarod tests; the relative content of macrophages was measured in the brain, malondialdehyde (MDA), the activity of antioxidant enzymes. Results. Under the influence of MPTP, the number of squares, rearings, body length and length is significantly less than in the intact group, and muscle tone is higher; in the brain the content of MDA and macrophages increases and the activity of superoxide dismutase (SOD) decreases. After the transplantation of adult donor ADSCs, the parameters of body and step length increase significantly, but not to the level of intact mice; the activity of SOD, glutathione reductase (GR) and the proportion of macrophages increase in the brain. After the administration of ADSCs of aging donors, the values of behavioural parameters and the proportion of macrophages in the brain correspond to the control group (only MPTP), and the activity of SOD corresponds to intact animals. In mice treated with ADSCs of aging donors in combination with melatonin, the direction of changes in behavioural parameters, SOD and GR activity, macrophage percentage was similar to that observed after the administration of adult donor ADSCs. Conclusions. The effects of ADSCs transplantation in mice with the MPTP model of parkinsonism depend on the age of the donor and are more pronounced in transplanted cells derived from adult mice. The effects of ADSCs from aging donors in combination with melatonin are consistent with those observed after administration of cells from adult donors.","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46782069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Bondariev, S. Strafun, Y. Holiuk, K. Saulenko, O. Darovskyi, A. Syvak
Recent studies show that among people with an active lifestyle about 6-10 % of injuries are acute injuries of the knee joints, namely – meniscus tear. The main treatment options for traumatic meniscus tears include surgical arthroscopic partial meniscectomy or meniscus reconstruction, and conservative regenerative injection techniques. Today, the choice of treatment tactics remains controversial. The purpose of the study was to evaluate the effectiveness of regenerative injection techniques in comparison with partial resection of the menisci and non-steroidal anti-inflammatory drugs together with the systematic use of kinesiotherapy for traumatic meniscus injuries. Materials and methods. The results of еру treatment of 154 patients with traumatic meniscus injuries were evaluated. Group 1 (n = 53) received intra-articular injection of plasma enriched with growth factors with a high platelet concentration of at least 1 million/μL and a high number of leukocytes (L-PRP/L-PCP) in combination with low molecular weight hyaluronic acid; the number of injections from 3 to 6 with an interval between injections of 2 weeks. Group 2 (n = 49) received NSAID therapy (orally, 1 tablet twice daily, 7 days with a break of 1 week) for 2 months and a course of physiotherapy exercises. Patients in group 3 underwent arthroscopic partial meniscectomy, followed by recommendations for motor regime. Evaluations were performed using VAS scale, WOMAC questionnaire and KOOS survey scale at 3, 6, 12, 24, and 36 months after the end of treatment. Results. The obtained results demonstrated the effectiveness of intra-articular use of L-PRP/L-PCP in the treatment of traumatic meniscus tears in the short term (up to 3 months) and in the long term (up to 3 years), represented by the improvement of joint function and a significant reduction in the level of pain, which was observed in patients of group №1 after 36 months: by VAS 1.2 ± 0.5 cm, questionnaire KOOS 94.5 ± 4.8 points, and WOMAC 4.0 ± 1.9, (p <0.05). The use of nonsteroidal anti-inflammatory drugs and physiotherapy exercises is not effective in the short term (3-6 months), and over time the condition of patients only worsens: after 36 months VAS 7.6 ± 1.9 cm, KOOS questionnaire 24.9 ± 3 , 9 points (p < 0.05), and WOMAC 72.2 ± 7.1, (p < 0.01 compared to primary data). Partial arthroscopic meniscal resection can reduce pain and restore functional status to satisfactory within one year, with further progression of pain symptoms and functional limitations in the second and third year of the study, which is reflected in the results after 36 months: for VAS 5.7 ± 1.9 cm, questionnaire for COOS 47.1 ± 5.7 points, and WOMAC 64.1 ± 5.9, (p < 0.05 compared to primary data). Conclusion. Intra-articular administration of L-PRP/L-PCP with hyaluronic acid can improve functionality and reduce pain in patients with traumatic meniscus injuries for up to 3 years. The use of NSAIDs and kinesiotherapy is not effective at all stages of follow
{"title":"Comparative analysis of the use of L-PRP/L-PCP injections, arthroscopic partial resection and nonsteroidal anti-inflammatory drugs in the treatment of the meniscus tears","authors":"G. Bondariev, S. Strafun, Y. Holiuk, K. Saulenko, O. Darovskyi, A. Syvak","doi":"10.22494/cot.v10i1.133","DOIUrl":"https://doi.org/10.22494/cot.v10i1.133","url":null,"abstract":"Recent studies show that among people with an active lifestyle about 6-10 % of injuries are acute injuries of the knee joints, namely – meniscus tear. The main treatment options for traumatic meniscus tears include surgical arthroscopic partial meniscectomy or meniscus reconstruction, and conservative regenerative injection techniques. Today, the choice of treatment tactics remains controversial. The purpose of the study was to evaluate the effectiveness of regenerative injection techniques in comparison with partial resection of the menisci and non-steroidal anti-inflammatory drugs together with the systematic use of kinesiotherapy for traumatic meniscus injuries. Materials and methods. The results of еру treatment of 154 patients with traumatic meniscus injuries were evaluated. Group 1 (n = 53) received intra-articular injection of plasma enriched with growth factors with a high platelet concentration of at least 1 million/μL and a high number of leukocytes (L-PRP/L-PCP) in combination with low molecular weight hyaluronic acid; the number of injections from 3 to 6 with an interval between injections of 2 weeks. Group 2 (n = 49) received NSAID therapy (orally, 1 tablet twice daily, 7 days with a break of 1 week) for 2 months and a course of physiotherapy exercises. Patients in group 3 underwent arthroscopic partial meniscectomy, followed by recommendations for motor regime. Evaluations were performed using VAS scale, WOMAC questionnaire and KOOS survey scale at 3, 6, 12, 24, and 36 months after the end of treatment. Results. The obtained results demonstrated the effectiveness of intra-articular use of L-PRP/L-PCP in the treatment of traumatic meniscus tears in the short term (up to 3 months) and in the long term (up to 3 years), represented by the improvement of joint function and a significant reduction in the level of pain, which was observed in patients of group №1 after 36 months: by VAS 1.2 ± 0.5 cm, questionnaire KOOS 94.5 ± 4.8 points, and WOMAC 4.0 ± 1.9, (p <0.05). The use of nonsteroidal anti-inflammatory drugs and physiotherapy exercises is not effective in the short term (3-6 months), and over time the condition of patients only worsens: after 36 months VAS 7.6 ± 1.9 cm, KOOS questionnaire 24.9 ± 3 , 9 points (p < 0.05), and WOMAC 72.2 ± 7.1, (p < 0.01 compared to primary data). Partial arthroscopic meniscal resection can reduce pain and restore functional status to satisfactory within one year, with further progression of pain symptoms and functional limitations in the second and third year of the study, which is reflected in the results after 36 months: for VAS 5.7 ± 1.9 cm, questionnaire for COOS 47.1 ± 5.7 points, and WOMAC 64.1 ± 5.9, (p < 0.05 compared to primary data). Conclusion. Intra-articular administration of L-PRP/L-PCP with hyaluronic acid can improve functionality and reduce pain in patients with traumatic meniscus injuries for up to 3 years. The use of NSAIDs and kinesiotherapy is not effective at all stages of follow","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45909767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Liubich, L. Staino, D. Egorova, V. Medvedev, N. Oleksenko, S. Verbovska, L. Pichkur, V. Tsymbaliuk
{"title":"Structural changes of spinal cord tissue of rats with experimental spinal cord injury after implantation of fibrin matrix associated with neural and mesenchymal progenitor cells","authors":"L. Liubich, L. Staino, D. Egorova, V. Medvedev, N. Oleksenko, S. Verbovska, L. Pichkur, V. Tsymbaliuk","doi":"10.22494/cot.v10i1.135","DOIUrl":"https://doi.org/10.22494/cot.v10i1.135","url":null,"abstract":"","PeriodicalId":36461,"journal":{"name":"Cell and Organ Transplantology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42055254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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