title: Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy.
abstract: We compared therapeutic benefits of intramyocardial injection of unfractionated bone marrow cells (BMCs) versus BMC extract as treatments for myocardial infarction (MI), using closed-chest ultrasound-guided injection at a clinically relevant time post-MI. MI was induced in mice and the animals treated at day 3 with either: (i) BMCs from green fluorescent protein (GFP)-expressing mice (n = 14), (ii) BMC extract (n = 14), or (iii) saline control (n = 14). Six animals per group were used for histology at day 6 and the rest followed to day 28 for functional analysis. Ejection fraction was similarly improved in the BMC and extract groups versus control (40.6 +/- 3.4 and 39.1 +/- 2.9% versus 33.2 +/- 5.0%, P < 0.05) with smaller scar sizes. At day 6 but not day 28, both therapies led to significantly higher capillary area and number of arterioles versus control. At day 6, BMCs increased the number of cycling cardiomyocytes (CMs) versus control whereas extract therapy resulted in significant reduction in the number of apoptotic CMs at the border zone (BZ) versus control. Intracellular components within BMCs can enhance vascularity, reduce infarct size, improve cardiac function, and influence CM apoptosis and cycling early after therapy following MI. Intact cells are not necessary and death of implanted cells may be a major component of the benefit.
authors.affiliation: Department of Medicine, University of California-San Francisco, 94143-0103, USA. yeghiaza@medicine.ucsf.edu
authors.forename: Yerem
authors.initials: Y
authors.lastname: Yeghiazarians
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Megha
authors.initials: M
authors.lastname: Prasad
authors.forename: Henry
authors.initials: H
authors.lastname: Shih
authors.forename: Shereen A
authors.initials: SA
authors.lastname: Saini
authors.forename: Junya
authors.initials: J
authors.lastname: Takagawa
authors.forename: Richard E
authors.initials: RE
authors.lastname: Sievers
authors.forename: Maelene L
authors.initials: ML
authors.lastname: Wong
authors.forename: Neel K
authors.initials: NK
authors.lastname: Kapasi
authors.forename: Rachel
authors.initials: R
authors.lastname: Mirsky
authors.forename: Juha
authors.initials: J
authors.lastname: Koskenvuo
authors.forename: Petros
authors.initials: P
authors.lastname: Minasi
authors.forename: Jianqin
authors.initials: J
authors.lastname: Ye
authors.forename: Mohan N
authors.initials: MN
authors.lastname: Viswanathan
authors.forename: Franca S
authors.initials: FS
authors.lastname: Angeli
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Boyle
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Springer
authors.forename: William
authors.initials: W
authors.lastname: Grossman
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism / Q000502:physiology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D004452:Echocardiography; D006321:Heart / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology