Abstract
Smooth muscle cells (SMCs) are key regulators of vascular disease and circulating smooth muscle progenitor cells may play important roles in vascular repair or remodelling. We developed enhanced protocols to derive smooth muscle progenitors from murine bone marrow and tested whether factors that are increased in atherosclerotic plaques, namely platelet-derived growth factor—BB (PDGF-BB) and monomeric collagen, can influence the smooth muscle specific differentiation, proliferation, and survival of mouse bone marrow-derived progenitor cells. During a 21 day period of culture, bone marrow cells underwent a marked increase in expression of the SMC markers α-SMA (1.93 ± 0.15 vs. 0.0008 ± 0.0003 (ng/ng GAPDH) at 0 d), SM22-α (1.50 ± 0.27 vs. 0.005 ± 0.001 (ng/ng GAPDH) at 0 d) and SM-MHC (0.017 ± 0.004 vs. 0.001 ± 0.001 (ng/ng GAPDH) at 0 d). Bromodeoxyuridine (BrdU) incorporation experiments showed that in early culture, the smooth muscle progenitor subpopulation could be identified by high proliferative rates prior to the expression of smooth muscle specific markers. Culture of fresh bone marrow or smooth muscle progenitor cells with PDGF-BB suppressed the expression of α-SMA and SM22-α, in a rapidly reversible manner requiring PDGF receptor kinase activity. Progenitors cultured on polymerized collagen gels demonstrated expression of SMC markers, rates of proliferation and apoptosis similar to that of cells on tissue culture plastic; in contrast, cells grown on monomeric collagen gels displayed lower SMC marker expression, lower growth rates (319 ± 36 vs. 635 ± 97 cells/mm2), and increased apoptosis (5.3 ± 1.6% vs. 1.0 ± 0.5% (Annexin 5 staining)). Our data shows that the differentiation and survival of smooth muscle progenitors are critically affected by PDGF-BB and as well as the substrate collagen structure.
Highlights
It is becoming recognized that vascular smooth muscle progenitor cells (SMPCs) play important roles in vascular repair, remodelling and disease ([1, 2])
We developed enhanced protocols to derive smooth muscle progenitors from murine bone marrow and tested whether factors that are increased in atherosclerotic plaques, namely platelet-derived growth factor—BB (PDGF-BB) and monomeric collagen, can influence the smooth muscle specific differentiation, proliferation, and survival of mouse bone marrowderived progenitor cells
We showed that the viability and capacity to maintain a differentiated phenotype of bone marrow derived SMPCs are strongly influenced by monomeric collagen and PDGF-BB, factors that are increased in atherosclerotic plaques
Summary
It is becoming recognized that vascular smooth muscle progenitor cells (SMPCs) play important roles in vascular repair, remodelling and disease ([1, 2]). Lesion progression in mice can be limited by systemic CXCL12 injections resulting in the recruitment of circulating SMPCs [8] and human studies demonstrate that circulating SMPC levels are reduced in acute coronary syndromes as compared to stable angina [2] These studies suggest that bone marrow derived SMPCs may be important therapeutic targets that may be modified to favourably induce appropriate vascular remodelling. The monomeric collagen matrix stimulates SMC proliferation in contrast to the reduction of cell growth on fibrillar collagen [17, 18] These effects can be further enhanced when co-stimulated with plateletderived growth factor (PDGF-BB) which possesses potent mitogenic and inflammatory effects and participates in ECM remodeling and has been shown to promote proliferation and differentiation in adjacent SMCs [19,20,21]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
