To understand which growth factors/cytokines can affect migration of mesenchymal stem cells (MSCs) to injured tissues, we compared the effects of many (26) growth factors/cytokines on the migration activity of rabbit and human MSCs using a microchemotaxis chamber. Among them, platelet-derived growth factor (PDGF)-BB, PDGF-AB, epidermal growth factor (EGF), HB-EGF, transforming growth factor (TGF-alpha), insulin growth factor (IGF-I), hepatocyte growth factor (HGF), fibroblast growth factor (FGF-2), and thrombin consistently enhanced the migration of rabbit and human MSCs at appropriate concentrations. PDGF-BB showed the greatest effect on migration. Various combinations of these factors further enhanced the migration of MSCs, whereas combinations of factors that shared common cell-surface receptors did not induce the additive stimulation. On the other hand, some combinations, including that of FGF-2 or thrombin with PDGF-BB, suppressed the migration activity of MSCs. These findings suggest that combinations of growth factors are important to eliciting the maximal chemotactic effect. The factors that induced the migration of MSCs also enhanced their proliferation, suggesting that migration and proliferation can take place simultaneously. The above factors were also effective in stimulating the migration of fibroblasts, but thrombin alone selectively enhanced the migration of MSCs, suggesting that thrombin is useful to stimulate migration of MSCs without migration of fibroblasts.
This study investigates concanavalin A (ConA) as a novel factor that may enhance osteogenesis of mesenchymal stem cells (MSCs) in vitro. Various factors have been studied as promoting factors for MSC osteogenesis in vivo and in vitro. However, their safety, effectiveness, and cost may not be ideal. So, human MSCs were cultured in osteogenic medium in the presence or absence of ConA. We used calcium assays to compare the effects of ConA and BMP-2 on MSC calcification. Also enzyme-linked immunosorbent assay (ELISA) and quantitative PCR were used to evaluate the expression levels of bone specific markers. ConA was observed to enhance the calcification and this effect was comparable to that of BMP-2. Combination of ConA and BMP-2 further enhanced the calcification slightly but significantly. ConA also increased osteocalcin and BMP-2 protein levels in the medium of MSC cultures. Furthermore, ConA increased osteocalcin, RUNX2, BMP-2, and BMP-4 mRNA expression levels. However, gene expression pattern of MSCs stimulated by ConA was different from that observed with BMP-2. These results, taken together, suggest that ConA and BMP-2 enhance MSC osteogenesis via different pathways. The ConA-induced bone formation in MSC cultures may be useful in regenerative medicine or tissue engineering in clinical studies and in basic research on bone formation.
Transplantation of bone marrow mesenchymal stem cells (MSC), chondrocytes, osteoblasts, or muscle cells promotes regeneration. However, these cells adhere poorly to some scaffolds--depending upon the scaffold material--and are often damaged by proteases or mechanical stimuli at site of transplantation. We found, however, that MSC, chondrocytes, and osteoblasts--along with some other cells--that were exposed to phaseolus vulgaris erythroagglutinin (PHA-E) or concanavalin A (ConA) increased their adhesion capacity on plastic tissue culture dishes and on plates of hydroxyapatite, titanium and poly-DL-lactic-co-glycolic acid (PLGA), and that these cells, moreover, built up resistance to proteases and/or mechanical stimuli. Thus, lectins may have great potential in tissue engineering and cell therapy.
A 79‐year‐old male with bronchiectasis was referred to our clinic because of mild chest tightness on exertion. He had no history of hemoptysis. An electrocardiogram showed ST segment depression in leads V5‐6. Multi‐detector contrast‐enhanced computed tomography revealed no significant stenosis in either coronary artery; however, a huge racemose hemangioma of the bronchial artery (RHBA) was detected. In addition, arterial supply to the RHBA via the right coronary artery (RCA) and the left internal thoracic artery (LITA) was suspected. Adenosine‐loading myocardial scintigraphy images revealed segmental hypo‐perfusion in the left ventricular inferior wall. Selective bronchial artery angiography revealed the huge RHBA. In addition, both the RCA and LITA provided arterial supply to the RHBA. To the best of our knowledge, this case is the first to show multiple arterial supply resulting in a huge RHBA.
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