Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy.
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.
Yeghiazarians
Yerem
Y
Department of Medicine, University of California-San Francisco, 94143-0103, USA. yeghiaza@medicine.ucsf.edu
Zhang
Yan
Y
Prasad
Megha
M
Shih
Henry
H
Saini
Shereen A
SA
Takagawa
Junya
J
Sievers
Richard E
RE
Wong
Maelene L
ML
Kapasi
Neel K
NK
Mirsky
Rachel
R
Koskenvuo
Juha
J
Minasi
Petros
P
Ye
Jianqin
J
Viswanathan
Mohan N
MN
Angeli
Franca S
FS
Boyle
Andrew J
AJ
Springer
Matthew L
ML
Grossman
William
W
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