PMID- 29914756 OWN - NLM STAT- MEDLINE DCOM- 20190626 LR - 20210109 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 26 IP - 7 DP - 2018 Jul 5 TI - Age-Related Impaired Efficacy of Bone Marrow Cell Therapy for Myocardial Infarction Reflects a Decrease in B Lymphocytes. PG - 1685-1693 LID - S1525-0016(18)30218-1 [pii] LID - 10.1016/j.ymthe.2018.05.015 [doi] AB - 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. CI - Copyright (c) 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved. FAU - An, Songtao AU - An S AD - Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Cardiology, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, Henan 450003, China. FAU - Wang, Xiaoyin AU - Wang X AD - Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Ruck, Melissa A AU - Ruck MA AD - Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Rodriguez, Hilda J AU - Rodriguez HJ AD - Division of Cardiology, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Kostyushev, Dmitry S AU - Kostyushev DS AD - Division of Cardiology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Varga, Monika AU - Varga M AD - Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Luu, Emmy AU - Luu E AD - Division of Cardiology, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Derakhshandeh, Ronak AU - Derakhshandeh R AD - Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Suchkov, Sergey V AU - Suchkov SV AD - Center for Personalized Medicine, Sechenov University, Moscow, Russia; Department for Translational Medicine, Moscow Engineering Physical Institute, Moscow, Russia. FAU - Kogan, Scott C AU - Kogan SC AD - Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Hermiston, Michelle L AU - Hermiston ML AD - Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. FAU - Springer, Matthew L AU - Springer ML AD - Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Cardiology, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: matt.springer@ucsf.edu. LA - eng GR - R01 HL086917/HL/NHLBI NIH HHS/United States GR - R21 HL097129/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20180615 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 SB - IM MH - Aging/*physiology MH - Animals MH - B-Lymphocytes/*cytology MH - Bone Marrow/*physiology MH - Bone Marrow Cells/*cytology MH - Bone Marrow Transplantation/methods MH - Cell- and Tissue-Based Therapy/methods MH - Flow Cytometry/methods MH - Heart/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Myocardial Infarction/*physiopathology PMC - PMC6036225 OTO - NOTNLM OT - B lymphocyte OT - advanced age OT - aged OT - bone marrow OT - cell therapy OT - ejection fraction OT - infarct size OT - myocardial infarction OT - paracrine EDAT- 2018/06/20 06:00 MHDA- 2019/06/27 06:00 PMCR- 2019/07/05 CRDT- 2018/06/20 06:00 PHST- 2018/01/10 00:00 [received] PHST- 2018/05/17 00:00 [revised] PHST- 2018/05/18 00:00 [accepted] PHST- 2018/06/20 06:00 [pubmed] PHST- 2019/06/27 06:00 [medline] PHST- 2018/06/20 06:00 [entrez] PHST- 2019/07/05 00:00 [pmc-release] AID - S1525-0016(18)30218-1 [pii] AID - 10.1016/j.ymthe.2018.05.015 [doi] PST - ppublish SO - Mol Ther. 2018 Jul 5;26(7):1685-1693. doi: 10.1016/j.ymthe.2018.05.015. Epub 2018 Jun 15.