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IN VITRO COMPARISON OF THE IMMUNOREGULATORY EFFECTS OF BONE MARROW AND ADIPOSE DERIVED STEM CELLS.
Presenter: Lehao Wu, MD
Co-Authors: Yuan N; Rubin JP; Christensen J; Grahammar J; Ibrahim Z; Lee A; Schneeberger S; Sacks JM; Cooney DS; Brandacher G
Johns Hopkins Medical Institution

Background: Both bone marrow (BMSCs) and adipose-derived (ASCs) mesenchymal stem cells have recently been described as a promising strategy to promote transplant tolerance. However, the unique immunoregulatory properties of BMSCs and ASCs and their individual ability to suppress an alloimmune response have not been directly compared.

Methods: BMSCs and ASCs were isolated from Lewis, Brown Norway (BN), and ACI rats. In a mixed lymphocyte reaction (MLR), CFSE-labeled Lewis rat splenocytes were cultured either 1) alone, 2) with irradiated Lewis splenocytes, 3) with irradiated BN rat splenocytes, or 4) with phytohaemagglutinin (PHA). Group 3 and 4 were further co-cultured with either varying doses of sorted BMSCs or ASCs from different passages, or media harvested from stem cell cultures to assess for immunomodulatory effects. Additionally, in Group 3, MSCs were added on day 3 to the MLR (delayed regulation), or were removed after 3-day of co-culture from the MLR (interrupted regulation).

Results: BMSCs and ASCs of all strains showed similar biological properties, and displayed low immunogenicity. All allogeneic MLRs showed vigorous cell proliferation as compared to cultured cells from Groups 1 and 2. When added to allogeneic MLRs, both BMSCs and ASCs of different origins (recipient, donor and third party) significantly suppressed allogeneic and PHA stimulation in a dose-dependent manner (p<0.05). ASCs showed superiority in suppressing both allo and non-specific regulation as compared to BMSCs(p<0.05). Stem cell culture media alone, however, did not suppress proliferation in any group. Moreover, in both delayed and interrupted regulation settings, the suppressive effects diminished (suppression rate: 16.22% and 50.41%, respectively vs. 83.39%). Interestingly, the MSCs from late passage exhibited lower regulatory potentials (10.91% vs. 64.49%).

Conclusion: MSCs from different tissue origins exert immunomodulation in allo- and in PHA-induced stimulation, indicating immunoregulatory effects of this type of stem cells are non-specific. In addition, the regulatory potential correlates with cell senescence.


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