Effective engraftment but poor mid-term persistence of mononuclear and mesenchymal bone marrow cells in acute and chronic rat myocardial infarction.
Bone marrow cells are used with promising results for cell therapy after myocardial infarction (MI). We determined the survival and organ distribution of transplanted mononuclear (MNC) or mesenchymal (MSC) bone marrow cells, and the influence of cell type, cell number and application time. MNC and MSC (male Fischer 344 rats) were injected into the border zone of MI (syngeneic females) immediately or 7 days after LAD ligation (10(5) or 10(6) cells, 50 microl). After 0 h, 48 h, 5 days, 3 weeks and 6 weeks, DNA of heart, lung, liver, spleen, kidney, blood, bone marrow, brain and skeletal muscle was isolated and the number of donor cells determined by quantitative real-time PCR with Y-chromosome specific primers (each n>or=4). The percentage of donor-cells in the heart decreased rapidly from 34-80% of injected cells (0 h) to 0.3-3.5% (6 weeks) independent from cell type, number and application time. The absolute number increased after increasing injected cell number (10(6) vs. 10(5)). In the lung, MNC and MSC were found at 0 h (126+/-48 and 140+/-3 per million organ cells), but in liver and kidney, only few. At 48 h and 6 weeks, an increasing number of MNC, but not MSC, were detected in the spleen (6 weeks, 602+/-173 per million organ cells vs. 95+/-50 in the heart, P=0.02). In all other organs, only few or no grafted cells of either cell type were detected at these times. Organ distribution was independent from injection time. The low survival of grafted cells may limit their therapeutic impact, while their distribution to other organs must be considered in all cell therapy applications.
Müller-Ehmsen
Jochen
J
Laboratory of Muscle Research and Molecular Cardiology, Department of Internal Medicine III, University of Cologne, Kerpener Str. 62, 50937 Köln, Germany. muller.ehmsen@uni-koeln.de
Krausgrill
Benjamin
B
Burst
Volker
V
Schenk
Kerstin
K
Neisen
Uta C
UC
Fries
Jochen W U
JW
Fleischmann
Bernd K
BK
Hescheler
Jürgen
J
Schwinger
Robert H G
RH
D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D002454:Cell Differentiation; D002908:Chronic Disease; D005456:Fluorescent Dyes / Q000494:pharmacology; D006085:Graft Survival; D007211:Indoles / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D009203:Myocardial Infarction / Q000628:therapy*; D051381:Rats; D011916:Rats, Inbred F344
D005456:Fluorescent Dyes; D007211:Indoles; C007293:DAPI