Safety of Intravenous Autologous Bone Marrow-Derived Mesenchymal Cell Transplantation in 5 Patients With Reduced Left Ventricular Ejection Fraction.

Background: Although intracardiac injection or intracoronary delivery of mesenchymal stem cells (MSCs) has been reported, there have been few studies on the intravenous injection of MSCs, particularly in Japan. Methods and Results: Five patients with left ventricular ejection fraction (LVEF) ≤45% received 1.0×108 MSCs intravenously. The procedure did not induce significant changes in vital signs. One patient had an elevated body temperature after 1 day, but recovered spontaneously. Laboratory tests remained normal for 1 month after cell delivery. Computed tomography was performed after 1-2 years, and there was no evidence of malignancy. Conclusions: In this pilot study of patients with reduced LVEF, intravenous MSC delivery had no adverse effects.

Aligned electrospun siloxane-doped vaterite/poly(L-lactide) composite fibremats: evaluation of their tensile strength and cell compatibility.

Siloxane-doped vaterite (SiV)/poly(L-lactide) hybrid-composite (SiPVH) has been developed in our group as the bone repair material and successfully fabricated into a non-woven electrospun fibremat. The aim of this work is to prepare aligned electrospun SiPVH fibremats with varied SiV content and compare their tensile properties and cell compatibilities using mouse osteoblast-like cells. It was observed that the maximum stress exhibited some non-linear trend as a function of SiV content: the highest stress value was reached with 30 wt.% SiV and decreased significantly with more than 40 wt.% SiV. Cellular morphology and proliferation were taken under examination on both aligned and random electrospun SiPVH fibremats. The cells started to orient themselves only 3 h after seeding on the aligned fibremat and they continued to elongate along the fibres. The number of the cells cultured up to seven days on both random and aligned fibremats was well comparable; therefore the alignment did not show negative effect on the cellular proliferation.

Preparation of electrospun fiber mats using siloxane-containing vaterite and biodegradable polymer hybrids for bone regeneration.

An electrospun fiber mat using a new composite consisting of siloxane-containing vaterite (SiV) and poly(lactic-co-glycolic acid) (PLGA) (denoted by SiPLGVH) was prepared with the aim of applying it as a membrane for use in a guided bone regeneration (GBR) system. Another electrospun fiber mat using a previously described composite consisting of SiV and poly(L-lactic acid) (denoted by SiPVH) was also prepared as a comparative sample. SiPLG VH fiber mats showed superior results in terms of mechanical tensile properties and cellular behavior. Their elongation before failure was about eight times higher than that of SiPVH. The numbers of osteoblast-like cells that proliferated on the SiPLGVH fiber mats, regardless of the hydroxyapatite coating, were comparable to that of SiPVH. The cells spread more, two dimensionally, on the SiPLGVH fiber mats, since the pores between fibers were narrowed down because of swelling of the PLGA matrix during cell culture. This two-dimensional cellular proliferation quality on the SiPLGVH fiber mats is expected to be suitable for materials used in GBR, leading to control of infiltration of the soft tissue and great tissue integration with the surrounding tissue.

Preparation of electrospun poly(lactic acid)-based hybrids containing siloxane-doped vaterite particles for bone regeneration.

Siloxane/poly(L-lactic acid)/vaterite hybrid (SiPVH) fibremats constantly release calcium ions and ionic silicon species that have the potential to promote bone regeneration. In order to improve the mechanical properties of the SiPVH fibremats, the effect of various silixane-containing vaterite (denoted by SiV) content (10-60 wt%) on tensile properties was assessed. SiPVH fibremats with 30 wt% SiV content showed the highest tensile strength of 2.87 ± 0.39 MPa. Based on the energy-dissipation mechanism, failure initiated at the stress concentration points such as pores on the fibre surfaces or filler particles. In the case of the SiPVH fibremats with 20 and 30 wt% SiV, stress concentration occurred around the filler particles, where the applied energy was directly converted to small volume dilatation around the filler particles during failure of the fibres. This mechanism can be applied only when the material contains the polymer and the filler particles in specific ratios; 20 and 30 wt% filler content in the fibremat in this work. To coat the fibre surfaces with bone-like apatite SiPVH fibremats were soaked in modified simulated body fluid (1.5 SBF). Bone-like apatite formed on the surfaces of SiPVH fibremats with more than 30 wt% of SiV content in 1 day of soaking. These results reveal that the SiPVH fibremats containing 30 wt% SiV have suitable mechanical properties for bone filler materials.

Cellular migration to electrospun poly(lactic acid) fibermats.

Nonwoven fabrics prepared via an electrospinning method, so-called electrospun fibermats, are expected to be promising scaffold materials for bone tissue engineering. In the present work, poly(L-lactic acid) (PLLA) fibermats, consisting of fibers with diameters ranging from 1 to 10 µm, were prepared by electrospinning. Mouse osteoblast-like cells (MC3T3-E1) were seeded on the fibermats with various fiber diameters (10, 5 and 2 µm; they are denoted by samples A, B and C, respectively) and cultured in two different directions in order to compare the migration behaviours into the scaffold of the normal condition and the anti-gravity condition. The cells in/on the fibermats were observed by laser confocal microscopy to estimate the cellular migration ability into them. When the MC3T3-E1 cells were cultured in the normal direction, the thickness of their layer increased to approx. 90 µm in the sample A, consisting of 10-µm fibers after 13 days of culture, while that in the sample C, consisting of 2-µm fibers, did not increase. When the MC3T3-E1 cells were cultured in the anti-gravity condition, the thickness of the cell layer in the sample A increased to approx. 60 µm. These results mean that the MC3T3-E1 cells migrated into the inside of sample A in either the normal direction or the anti-gravity one. The cellular proliferation showed no significant difference among the fibermats with three different fiber diameters; MC3T3-E1 cells on the fibermat with 2 µm fiber diameter grew two-dimensionally, while they grew three-dimensionally in the fibermat with 10 µm fiber diameter.