Role of endogenous bone marrow cells in long-term repair mechanisms after myocardial infarction.
Homing and regenerative potential of endogenous bone marrow cells (BMC) in myocardial infarction (MI) is a controversial issue. Using human placental alkaline phosphatase (hPLAP) as genetic marker for cell tracking, we examined the influx of bone marrow-derived cells during tissue repair after the induction of MI over a study period of 17 weeks in wild-type inbred Fischer 344 rats, lethally irradiated and reconstituted with bone marrow (BM) from transgenic F344 rats expressing hPLAP under the control of the ubiquitous R26 promoter. During the early phases of tissue repair, hPLAP-positive macrophages, endothelial cells, fibroblasts and also myofibroblast-like cells were recruited from BM. However, only some hPLAP-positive endothelial cells, fibroblasts and myofibroblast-like cells persisted until 17 weeks after MI. With the exception of a single cell, there was no evidence of BM-derived cardiomyocytes throughout the study. Rather, some local cardiac progenitor cells appeared to differentiate into cardiomyocytes in the peri-infarct regions. In conclusion, our data show that the inflammation-induced influx of BM-derived cells into the infarction area is restricted to leukocytes, endothelial cells, fibroblasts and myofibroblast-like cells. Our long-term analysis casts doubt on the hypothesis that circulating BM-derived mesenchymal precursor cells participate in cardiomyogenesis after MI.
Odörfer
Kathrin I
KI
Institute of Pathophysiology, Department of Biomedical Sciences, University of Veterinary Medicine, Vienna 1210, Austria.
Walter
Ingrid
I
Kleiter
Miriam
M
Sandgren
Eric P
EP
Erben
Reinhold G
RG
D000199:Actins / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism*; D002452:Cell Count; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D016612:Paraffin Embedding; D051381:Rats; D055647:Rats, Transgenic; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing; D000097382:CD68 Molecule
D000199:Actins; D000469:Alkaline Phosphatase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014746:Vimentin; C067980:CD68 antigen, human; D000097382:CD68 Molecule