PMID- 19384293 OWN - NLM STAT- MEDLINE DCOM- 20091013 LR - 20211020 IS - 1525-0024 (Electronic) IS - 1525-0016 (Print) IS - 1525-0016 (Linking) VI - 17 IP - 7 DP - 2009 Jul TI - Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy. PG - 1250-6 LID - 10.1038/mt.2009.85 [doi] AB - 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. FAU - Yeghiazarians, Yerem AU - Yeghiazarians Y AD - Department of Medicine, University of California-San Francisco, 94143-0103, USA. yeghiaza@medicine.ucsf.edu FAU - Zhang, Yan AU - Zhang Y FAU - Prasad, Megha AU - Prasad M FAU - Shih, Henry AU - Shih H FAU - Saini, Shereen A AU - Saini SA FAU - Takagawa, Junya AU - Takagawa J FAU - Sievers, Richard E AU - Sievers RE FAU - Wong, Maelene L AU - Wong ML FAU - Kapasi, Neel K AU - Kapasi NK FAU - Mirsky, Rachel AU - Mirsky R FAU - Koskenvuo, Juha AU - Koskenvuo J FAU - Minasi, Petros AU - Minasi P FAU - Ye, Jianqin AU - Ye J FAU - Viswanathan, Mohan N AU - Viswanathan MN FAU - Angeli, Franca S AU - Angeli FS FAU - Boyle, Andrew J AU - Boyle AJ FAU - Springer, Matthew L AU - Springer ML FAU - Grossman, William AU - Grossman W LA - eng GR - R01 HL086917/HL/NHLBI NIH HHS/United States GR - R03 EB005802/EB/NIBIB NIH HHS/United States GR - R03EB005802/EB/NIBIB NIH HHS/United States GR - R01HL086917/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 - 20090421 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 SB - IM MH - Animals MH - Apoptosis MH - Bone Marrow Cells/metabolism/*physiology MH - Cell- and Tissue-Based Therapy/*methods MH - Echocardiography MH - Heart/*physiology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Myocardial Infarction/*therapy MH - Myocytes, Cardiac/cytology/physiology PMC - PMC2835212 EDAT- 2009/04/23 09:00 MHDA- 2009/10/14 06:00 PMCR- 2010/07/01 CRDT- 2009/04/23 09:00 PHST- 2009/04/23 09:00 [entrez] PHST- 2009/04/23 09:00 [pubmed] PHST- 2009/10/14 06:00 [medline] PHST- 2010/07/01 00:00 [pmc-release] AID - S1525-0016(16)31836-6 [pii] AID - 10.1038/mt.2009.85 [doi] PST - ppublish SO - Mol Ther. 2009 Jul;17(7):1250-6. doi: 10.1038/mt.2009.85. Epub 2009 Apr 21.