NDLI: Suspension-Expansion of Bone Marrow Results in Small Mesenchymal Stem Cells Exhibiting Increased Transpulmonary Passage Following Intravenous Administration.

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Suspension-Expansion of Bone Marrow Results in Small Mesenchymal Stem Cells Exhibiting Increased Transpulmonary Passage Following Intravenous Administration.

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Suspension-Expansion of Bone Marrow Results in Small Mesenchymal Stem Cells Exhibiting Increased Transpulmonary Passage Following Intravenous Administration.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zanetti, Andrea Grata, Michelle Etling, Emily B. Panday, Regeant Villanueva, Flordeliza S. Toma, Catalin
Description	Author Affiliation: Zanetti A ( 1 Heart and Vascular Institute, University of Pittsburgh and University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.); Grata M ( 1 Heart and Vascular Institute, University of Pittsburgh and University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.); Etling EB ( 1 Heart and Vascular Institute, University of Pittsburgh and University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.); Panday R ( 1 Heart and Vascular Institute, University of Pittsburgh and University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.); Villanueva FS ( 1 Heart and Vascular Institute, University of Pittsburgh and University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.); Toma C ( 2 The McGowan Center for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.)
Abstract	Mesenchymal stem cells (MSCs) have been extensively explored in a variety of regenerative medicine applications. The relatively large size of MSCs expanded in tissue culture flasks leads to retention in the microcirculation of the lungs following intravenous delivery, reducing their capacity to reach target sites. We explored whether the expansion of whole marrow in suspension cultures would yield smaller MSCs with increased capacity to traverse the pulmonary microcirculation compared with traditional monolayer cultures. We tested this hypothesis using rat marrow in a suspension bioreactor culture with fibronectin-coated microcarriers, leading to sustained expansion of both the microbead-adherent cells, as well as of a nonadherent cell fraction. Magnetic depletion of CD45(+) cells from the bioreactor cultures after 5 weeks led to a highly enriched CD73(+)/CD90(+)/CD105(+) MSC population. The bioreactor-grown MSCs were significantly smaller than parallel monolayer MSCs (15.1 ± 0.9 µm vs. 18.5 ± 2.3 µm diameter, p<0.05). When fluorescently labeled bioreactor-grown MSCs were intravenously injected into rats, the peak cell concentration in the arterial circulation was an order of magnitude higher than similarly delivered monolayer-grown MSCs (94.8 ± 29.6 vs. 8.2 ± 5.6/10(6) nucleated blood cells, respectively, p<0.05). At 24 h after intravenous injection of the LacZ-labeled bioreactor-grown MSCs, there was a significant threefold decrease in the LacZ-labeled MSCs trapped in the lungs, with a significant increase in the cells reaching the spleen and liver in comparison to their monolayer MSC counterparts. Bioreactor-grown whole marrow cell cultures yielded smaller MSCs with increased capacity to traverse the pulmonary microcirculation compared with traditionally expanded monolayer MSCs. This may significantly improve the capacity and efficiency of these cells to home to injury sites downstream of the lungs.
File Format	HTM / HTML
ISSN	21524947
e-ISSN	21524955
DOI	10.1089/ten.TEC.2014.0344
Journal	Tissue Engineering Part C: Methods
Issue Number	7
Volume Number	21
Language	English
Publisher	Mary Ann Liebert
Publisher Date	2015-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Biotechnology Bone Marrow Cell Movement Mesenchymal Stem Cell Transplantation Mesenchymal Stromal Cells Cytology Animals Bioreactors Cells, Cultured Immunomagnetic Separation Lung Rats, Sprague-dawley Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article

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