Abstract T P219: Customizing the Secretomes of Mesenchymal Stem Cells: Implications for Clinical Trials
Background: Extensive animal data indicate that mesenchymal stem cells (MSCs) improve outcome in stroke models. Systemic delivery either by IV or Intra-arterial(IA) injection of MSCs is a potential therapeutic intervention for stroke based on the broad repertoire of secreted trophic and immunomodulatory cytokines that MSCs produce. We determined if exposure of MSCs to different types of solutions and catheters relevant to IA injections will lead to differential secretion of cytokines and thereby alter the functionality of MSCs.
Methods: Passage 2 MSCs were derived from human bone marrow donated by a healthy volunteer and tested in the following: 5% albumin(Alb),6% Hexstarch(Hx) or 40% dextran(Dx). Each solution was tested in 3 forms: solution alone, with low dose (5 IU/ml) Heparin, with 10% Omnipaque, or the combination of heparin and omnipaque. 5 million MSCs were suspended in 1ml of respective solution for 5, 30 or 60 mins. At the end of each time point, cells were collected directly or passed through a catheter (PROWLER SELECT LP). Viability and cytokine release profiles were tested under various scenarios.
Results: Cell viability remained above 90% in all solutions tested, Alb being the highest at 98%, and was not reduced after catheter passage, exposure to heparin or Omnipaque. Catheter passage did not alter MSC cytokine secretion in almost all the cases (Fig). Alb led to increased release of angiogenic factors such as VEGF and IL-8 compared with other solutions while Hx and Dx led to suppression of inflammatory cytokines such as IL-6 and TNF-α.
Conclusions: Exposure of MSCs to certain types of solutions change the profile of cytokine secretion. The activation patterns of MSCs may therefore be affected by the solutions/vehicles used for these cells. It may thus be possible to customize the profile of MSC secretomes to selectively modify their cytokine expression and individualize stem cell treatment to preferentially enhance or downregulate specific biological effects.
Author Disclosures: O. Mir: Research Grant; Significant; NIH T-32, SPORTIAS P32. K. Parsha: None. B. Yang: None. P. Hanely: None. A. Gee: None. J. Aronowski: None. S. Savitz: Research Grant; Significant; NIH RO1.
- © 2014 by American Heart Association, Inc.