Age-Related Impaired Efficacy of Bone Marrow Cell Therapy for Myocardial Infarction Reflects a Decrease in B Lymphocytes
An S., Wang X., Ruck M. A., Rodriguez H. J., Kostyushev D. S., Varga M., Luu E., Derakhshandeh R., Suchkov S. V., Kogan S. C., Hermiston M. L., Springer M. L.
Molecular Therapy
Vol.26, Issue7, P. 1685-1693
Опубликовано: 2018
Тип ресурса: Статья
DOI:10.1016/j.ymthe.2018.05.015
Аннотация:
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, wh
Ключевые слова:
advanced age; aged; B lymphocyte; bone marrow; cell therapy; ejection fraction; infarct size; myocardial infarction; paracrine
age; animal cell; animal experiment; animal model; animal tissue; Article; B lymphocyte; bone marrow transplantation; controlled study; depletion; flow cytometry; heart function; heart infarction; heart infarction size; infant; male; mouse; nonhuman; paracrine signaling; T lymphocyte; aging; animal; B lymphocyte; biological therapy; bone marrow; bone marrow cell; bone marrow transplantation; C57BL mouse; cytology; heart; heart infarction; pathophysiology; physiology; procedures; Aging; Animals; B-Lymphocytes; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Cell- and Tissue-Based Therapy; Flow Cytometry; Heart; Male; Mice; Mice, Inbred C57BL; Myocardial Infarction
Язык текста: Английский
ISSN: 1525-0024
An S.
Wang X.
Ruck M. A.
Rodriguez H. J.
Kostyushev D. S.
Varga M.
Luu E.
Derakhshandeh R.
Suchkov S. V. Sergej Viktorovich 1957-
Kogan S. C.
Hermiston M. L.
Springer M. L.
Ан С.
Wанг Х.
Руcк М. А.
Родригуез Х. Й.
Костюшев Д. С.
Варга М.
Луу Е.
Дерахшандех Р.
Сучков С. В. Сергей Викторович 1957-
Коган С. C.
Хермистон М. Л.
Спрингер М. Л.
Age-Related Impaired Efficacy of Bone Marrow Cell Therapy for Myocardial Infarction Reflects a Decrease in B Lymphocytes
Текст визуальный непосредственный
Molecular Therapy
Academic Press
Vol.26, Issue7 P. 1685-1693
2018
Статья
advanced age aged B lymphocyte bone marrow cell therapy ejection fraction infarct size myocardial infarction paracrine
age animal cell animal experiment animal model animal tissue Article B lymphocyte bone marrow transplantation controlled study depletion flow cytometry heart function heart infarction heart infarction size infant male mouse nonhuman paracrine signaling T lymphocyte aging animal B lymphocyte biological therapy bone marrow bone marrow cell bone marrow transplantation C57BL mouse cytology heart heart infarction pathophysiology physiology procedures Aging Animals B-Lymphocytes Bone Marrow Bone Marrow Cells Bone Marrow Transplantation Cell- and Tissue-Based Therapy Flow Cytometry Heart Male Mice Mice, Inbred C57BL Myocardial Infarction
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, wh