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Age-Related Impaired Efficacy of Bone Marrow Cell Therapy for Myocardial Infarction Reflects a Decrease in B Lymphocytes
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05.07.2018 |
An S.
Wang X.
Ruck M.
Rodriguez H.
Kostyushev D.
Varga M.
Luu E.
Derakhshandeh R.
Suchkov S.
Kogan S.
Hermiston M.
Springer M.
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Molecular Therapy |
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1 |
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© 2018 The American Society of Gene and Cell Therapy Treatment of myocardial infarction (MI) with bone marrow cells (BMCs) improves post-MI cardiac function in rodents. However, clinical trials of BMC therapy have been less effective. While most rodent experiments use young healthy donors, patients undergoing autologous cell therapy are older and post-MI. We previously demonstrated that BMCs from aged and post-MI donor mice are therapeutically impaired, and that donor MI induces inflammatory changes in BMC composition including reduced levels of B lymphocytes. Here, we hypothesized that B cell alterations in bone marrow account for the reduced therapeutic potential of post-MI and aged donor BMCs. Injection of BMCs from increasingly aged donor mice resulted in progressively poorer cardiac function and larger infarct size. Flow cytometry revealed fewer B cells in aged donor bone marrow. Therapeutic efficacy of young healthy donor BMCs was reduced by depletion of B cells. Implantation of intact or lysed B cells improved cardiac function, whereas intact or lysed T cells provided only minor benefit. We conclude that B cells play an important paracrine role in effective BMC therapy for MI. Reduction of bone marrow B cells because of age or MI may partially explain why clinical autologous cell therapy has not matched the success of rodent experiments. Implantation of bone marrow cells into mouse hearts after myocardial infarction is therapeutic, but if the cells are from donors that are older or post-MI (mimicking autologous cell therapy), they are less effective. This report presents evidence that a decrease in B lymphocytes is responsible for the reduced therapeutic response.
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The hardware techniques for the restoration of the gait stereotype in the patients following total hip replacement: the personalized approach
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09.04.2018 |
Koneva E.
Lyadov K.
Shapovalenko T.
Zhukova E.
Polushkin V.
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Voprosy kurortologii, fizioterapii, i lechebnoi fizicheskoi kultury |
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0 |
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BACKGROUND: total hip replacement has long ago become the «golden standard» for the treatment of dysplastic coxarthrosis in thousands of the patients receiving it every year. In the meantime, the analysis of the specialized literature gives evidence of the lack of a systematic and personified approach to the rehabilitation treatment. AIM: The objective of the present study was to improve medical rehabilitation of the patients following the total hip replacement and to develop the personalized programs for walking modality reconstruction taking into consideration the age and the body weight of the patients. PATIENTS AND METHODS: A total of 240 patients were available for the observation including 184 women and 56 men. They were divided into three study groups and one control group, with the differentiation into the following three subgroups: one comprised of the patients of moderate acerage age and body weight, the other containing the obese patients (BMI>35), and the third one involving the elderly patients (age >70 years); each subgroup consisted of 20 patients. All the patients received the early basic rehabilitation treatment, those in the study groups had to perform in addition the robotic training based on the use of hardware techniques supplemented by passive mechanotherapy and electromyostimulation designed to restore the walking stereotype with three types of devices: body weight unloading, video-reconstruction associated with biological feedback and robototherapy. RESULTS: The comparative analysis of the effectiveness of various methods of gait reconstruction has demonstrated the high effectiveness of the application of the hardware technique in the patients of moderate acerage age and body weight. At the same time, the elderly patients had a significantly higher rate of successful walking reconstruction efficiency under the influence of the video-associated training with biological feedback (3 times that achieved with training using the device for unloading the body weight and 4 times compared with the result of a course of robotic walk. The evaluation of the application of the techniques for the gait stereotype reconstruction in the obese patients gave evidence of the advantage of the Lokomat robotic trainings that produced 6 times better results than unloading of the body weight and 5 times better ones than the video-associated training with biological feedback. DISCUSSION: The results of the present study are on the whole comparable with the data reported by other authors although its design was different from that of the majority of the published studies in that our patients were allocated to different subgroups for the further personalization of the methods applied to restore the gait stereotype. The factors limiting the use of the results of this study include the medium-high level of the patients' welfare most of whom are residents of the city of Moscow and Moscow region characterized by a relatively high quality and accessibility of health care. It means that the results of such studies as the one described in the present article are directly related to the quality and accessibility of health care and can be extrapolated only to the socially safe and well-to-do patients. CONCLUSIONS: All the hardware techniques are equally effective in the patients of moderate average age and body weight. The elderly patients showed the best results using the video-reconstruction associated with biological feedback, while the Locomat technique was especially useful for the obese patients.
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