title: Donor myocardial infarction impairs the therapeutic potential of bone marrow cells by an interleukin-1-mediated inflammatory response.
abstract: Delivery of bone marrow cells (BMCs) to the heart has substantially improved cardiac function in most rodent models of myocardial infarction (MI), but clinical trials of BMC therapy have led to only modest improvements. Rodent models typically involve intramyocardial injection of BMCs from distinct donor individuals who are healthy. In contrast, autologous BMCs from individuals after MI are used for clinical trials. Using BMCs from donor mice after MI, we discovered that recent MI impaired BMC therapeutic efficacy. MI led to myocardial inflammation and an increased inflammatory state in the bone marrow, changing the BMC composition and reducing their efficacy. Injection of a general anti-inflammatory drug or a specific interleukin-1 inhibitor to donor mice after MI prevented this impairment. Our findings offer an explanation of why human trials have not matched the success of rodent experiments and suggest potential strategies to improve the success of clinical autologous BMC therapy.
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Wang
authors.forename: Junya
authors.initials: J
authors.lastname: Takagawa
authors.forename: Viola C
authors.initials: VC
authors.lastname: Lam
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Haddad
authors.forename: Diana L
authors.initials: DL
authors.lastname: Tobler
authors.forename: Pamela Y
authors.initials: PY
authors.lastname: Mok
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Brian T
authors.initials: BT
authors.lastname: Clifford
authors.forename: Kranthi
authors.initials: K
authors.lastname: Pinnamaneni
authors.forename: Shereen A
authors.initials: SA
authors.lastname: Saini
authors.forename: Robert
authors.initials: R
authors.lastname: Su
authors.forename: Maya J
authors.initials: MJ
authors.lastname: Bartel
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.forename: Larry
authors.initials: L
authors.lastname: Carbone
authors.forename: Scott
authors.initials: S
authors.lastname: Kogan
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.forename: Michelle
authors.initials: M
authors.lastname: Hermiston
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Springer
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D004452:Echocardiography; D005434:Flow Cytometry; D007375:Interleukin-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D014019:Tissue Donors
chemical_list: D007375:Interleukin-1