Effects of Extracellular Matrix on Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells into Smooth Muscle Cell Lineage: Utility for Cardiovascular Tissue Engineering

Abstract

Background: Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into various types of cell, and the extracellular matrix (ECM) is acknowledged to be important for the regulation of cell functions. In this study, we demonstrated the effects of ECMs on the differentiation of human bone marrow-derived MSCs into a smooth muscle cell (SMC) lineage. Methods: Human MSCs (hMSCs) were cultured on dishes coated with 3 types of ECM including laminin (LM), collagen type IV (Col-IV) and fibronectin for 7 days, and simultaneously cultured on a noncoated dish as a control. Cell numbers of these cultured hMSCs were counted, and their expression of SMC-specific genes and proteins was evaluated. hMSCs were then seeded on LM-coated biodegradable sheets and implanted into rat subcutaneous space. After 2 weeks of implantation, these tissues were evaluated. Results: The number of hMSCs was significantly increased by culture on Col-IV-coated dishes. The expression of SMC-specific genes and proteins (α-smooth muscle actin, ASMA; h1-calponin, CALP) in hMSC was significantly upregulated from culture on LM-coated dishes. LM-coated sheets showed a significantly increased expression of ASMA and CALP protein in vivo. Moreover, a fully differentiated marker (SM2) was expressed in the in vivo implanted hMSCs in the course of 2 weeks on the LM-coated sheet. Conclusion: These results suggest that the signal transduction of the cell-matrix interaction for the differentiation of hMSCs into SMCs was activated when cultured with LM. LM-coated materials may thus be useful for cardiovascular tissue engineering.

Decellularized ECM effects on human mesenchymal stem cell stemness and differentiation

“…9). It previously was established that ECM can induce hMSC to the smooth muscle cell lineage (Lozito et al, 2009; Suzuki et al, 2010). Our results indicate, however, that the A7r5-ECM and myomSMC-ECMs had different effects on the process of naïve hMSCs smooth muscle cell differentiation.…”

Mesenchymal stem cells attenuate angiotensin II-induced aortic aneurysm growth in apolipoprotein E-deficient mice

“…MSCs used for cell tracking studies (n ϭ 3) were labeled with the fluorescent cell linker PKH26 (Sigma-Aldrich, St. Louis, Mo) before the 7-day incubation period. 17 The culture temperature was then decreased from 37°C to 22°C, and the MSCs detached spontaneously and floated up as sheets into the culture medium. Laparotomy and abdominal aortic exposure only were performed on control mice (group 2, n ϭ 6).…”

Optimization of hyperthermia and dendritic cell immunotherapy for squamous cell carcinoma

“…expression of Hsp70 by heated sccVII cells was evaluated by Western blotting, according to a previous study (9). Mouse anti-Hsp70 antibody (clone, c92F3A-5; stressgen Biotechnologies, Bc, canada; 1:1000) was used as a primary antibody.…”