title: Influence of cell treatment with PDGF-BB and reperfusion on cardiac persistence of mononuclear and mesenchymal bone marrow cells after transplantation into acute myocardial infarction in rats.
abstract: Bone marrow cells are used for cell therapy after myocardial infarction (MI) with promising results. However, cardiac persistence of transplanted cells is rather low. Here, we investigated strategies to increase the survival and cardiac persistence of mononuclear (MNC) and mesenchymal (MSC) bone marrow cells transplanted into infarcted rat hearts. MNC and MSC (male Fischer 344 rats) were treated with different doses of PDGF-BB prior to intramyocardial injection into border zone of MI (syngeneic females, permanent LAD ligation) and hearts were harvested after 5 days and 3 weeks. In additional experiments, untreated MNC and MSC were injected immediately after permanent or temporary LAD ligation and hearts were harvested after 48 h, 5 days, 3 weeks, and 6 weeks. DNA of the hearts was isolated and the number of donor cells was determined by quantitative real-time PCR with Y chromosome-specific primers. There was a remarkable though not statistically significant (p = 0.08) cell loss of approximately 46% between 5 days and 3 weeks in the control group, which was completely inhibited by treatment with high dose of PDGF-BB. Forty-eight hours after reperfusion only 10% of injected MSC or 1% for MNC were found in the heart, decreasing to 1% for MSC and 0.5% for MNC after 6 weeks. These numbers were lower than after permanent LAD ligation for both MNC and MSC at all time points studied. Treatment with PDGF-BB seems to prevent loss of transplanted bone marrow cells at later times presumably by inhibition of apoptosis, while reperfusion of the occluded artery enhances cell loss at early times putatively due to enhanced early wash-out. Further investigations are needed to substantially improve the persistence and survival of grafted bone marrow cells in infarcted rat hearts, in order to fully explore the therapeutic potential of this novel treatment modality for myocardial repair.
authors.affiliation: Department III of Internal Medicine, University Hospital of Cologne, Köln, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Krausgrill
authors.forename: Marius
authors.initials: M
authors.lastname: Vantler
authors.forename: Volker
authors.initials: V
authors.lastname: Burst
authors.forename: Martin
authors.initials: M
authors.lastname: Raths
authors.forename: Marcel
authors.initials: M
authors.lastname: Halbach
authors.forename: Konrad
authors.initials: K
authors.lastname: Frank
authors.forename: Silke
authors.initials: S
authors.lastname: Schynkowski
authors.forename: Kerstin
authors.initials: K
authors.lastname: Schenk
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: Jochen
authors.initials: J
authors.lastname: Müller-Ehmsen
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000077214:Becaplermin; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D016026:Bone Marrow Transplantation / Q000379:methods; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology / Q000637:transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D009203:Myocardial Infarction / Q000503:physiopathology / Q000628:therapy*; D015425:Myocardial Reperfusion; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology* / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D011916:Rats, Inbred F344; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D043925:Angiogenesis Inducing Agents; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; C075278:platelet-derived growth factor A; D000077214:Becaplermin