PMID- 14963008 OWN - NLM STAT- MEDLINE DCOM- 20040621 LR - 20181130 IS - 1524-4571 (Electronic) IS - 0009-7330 (Linking) VI - 94 IP - 5 DP - 2004 Mar 19 TI - Platelet-derived growth factor-AB promotes the generation of adult bone marrow-derived cardiac myocytes. PG - E39-45 AB - The directed generation of cardiac myocytes from endogenous stem cells offers the potential for novel therapies for cardiovascular disease. To facilitate the development of such approaches, we sought to identify and exploit the pathways directing the generation of cardiac myocytes from adult rodent bone marrow cells (BMCs). In vitro cultures supporting the spontaneous generation of functional cardiac myocytes from murine BMCs demonstrated induced expression of platelet-derived growth factor (PDGF)-A and -B isoforms with alpha- and beta-myosin heavy chains as well as connexin43. Supplementation of PDGF-AB speeded the kinetics of myocyte development in culture by 2-fold. In a rat heart, myocardial infarction pretreatment model PDGF-AB also promoted the derivation of cardiac myocytes from BMCs, resulting in a significantly greater number of islands of cardiac myocyte bundles within the myocardial infarction scar compared with other treatment groups. However, gap junctions were detected only between the cardiac myocytes receiving BMCs alone, but not BMCs injected with PDGF-AB. Echocardiography and exercise testing revealed that the functional improvement of hearts treated with the combination of BMCs and PDGF-AB was no greater than with injections of BMCs or PDGF-AB alone. These studies demonstrated that PDGF-AB enhances the generation of BMC-derived cardiac myocytes in rodent hearts, but suggest that alterations in cellular patterning may limit the functional benefit from the combined injection of PDGF-AB and BMCs. Strategies based on the synergistic interactions of PDGF-AB and endogenous stem cells will need to maintain cellular patterning in order to promote the restoration of cardiac function after acute coronary occlusion. FAU - Xaymardan, Munira AU - Xaymardan M AD - Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. FAU - Tang, Lilong AU - Tang L FAU - Zagreda, Leze AU - Zagreda L FAU - Pallante, Benedetta AU - Pallante B FAU - Zheng, Jingang AU - Zheng J FAU - Chazen, Joseph L AU - Chazen JL FAU - Chin, Andrew AU - Chin A FAU - Duignan, Inga AU - Duignan I FAU - Nahirney, Patrick AU - Nahirney P FAU - Rafii, Shahin AU - Rafii S FAU - Mikawa, Takashi AU - Mikawa T FAU - Edelberg, Jay M AU - Edelberg JM LA - eng GR - AG19738/AG/NIA NIH HHS/United States GR - AG20918/AG/NIA NIH HHS/United States GR - HL54128/HL/NHLBI NIH HHS/United States GR - HL62175/HL/NHLBI NIH HHS/United States GR - HL67150/HL/NHLBI NIH HHS/United States GR - HL67839/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. DEP - 20040212 PL - United States TA - Circ Res JT - Circulation research JID - 0047103 RN - 0 (Platelet-Derived Growth Factor) RN - 0 (RNA, Messenger) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (platelet-derived growth factor AB) RN - 103107-01-3 (Fibroblast Growth Factor 2) SB - IM MH - Animals MH - Bone Marrow Cells/cytology/*drug effects MH - Bone Marrow Transplantation MH - Cell Differentiation/drug effects MH - Computer Systems MH - Exercise Test MH - Fibroblast Growth Factor 2/pharmacology MH - Mesenchymal Stem Cell Transplantation MH - Mesenchymal Stem Cells/cytology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Microscopy, Video MH - Myocardial Infarction/diagnostic imaging/drug therapy/pathology/therapy MH - Myocytes, Cardiac/*cytology MH - Platelet-Derived Growth Factor/genetics/pharmacology/*physiology/therapeutic use MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Inbred F344 MH - Ultrasonography MH - Vascular Endothelial Growth Factor A/pharmacology EDAT- 2004/02/14 05:00 MHDA- 2004/06/23 05:00 CRDT- 2004/02/14 05:00 PHST- 2004/02/14 05:00 [pubmed] PHST- 2004/06/23 05:00 [medline] PHST- 2004/02/14 05:00 [entrez] AID - 01.RES.0000122042.51161.B6 [pii] AID - 10.1161/01.RES.0000122042.51161.B6 [doi] PST - ppublish SO - Circ Res. 2004 Mar 19;94(5):E39-45. doi: 10.1161/01.RES.0000122042.51161.B6. Epub 2004 Feb 12.