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Sci Rep. 2018 May 1;8(1):6816. doi: 10.1038/s41598-018-24971-2.

Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction.

Author information

1
Center for Surgery, Innovation, and Bioengineering, Department of Surgery, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts, 02114, USA.
2
Center for Surgery, Innovation, and Bioengineering, Department of Surgery, Massachusetts General Hospital, Harvard Medical School and the Shriners Hospitals for Children, Boston, Massachusetts, 02114, USA. biju_parekkadan@hms.harvard.edu.
3
Harvard Stem Cell Institute, Cambridge, Massachusetts, 02138, USA. biju_parekkadan@hms.harvard.edu.
4
Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, 08854, USA. biju_parekkadan@hms.harvard.edu.

Abstract

Despite widespread preclinical success, mesenchymal stromal cell (MSC) therapy has not reached consistent pivotal clinical endpoints in primary indications of autoinflammatory diseases. Numerous studies aim to uncover specific mechanisms of action towards better control of therapy using in vitro immunomodulation assays. However, many of these immunomodulation assays are imperfectly designed to accurately recapitulate microenvironment conditions where MSCs act. To increase our understanding of MSC efficacy, we herein conduct a systems level microenvironment approach to define compartmental features that can influence the delivery of MSCs' immunomodulatory effect in vitro in a more quantitative manner than ever before. Using this approach, we notably uncover an improved MSC quantification method with predictive cross-study applicability and unveil the key importance of system volume, time exposure to MSCs, and cross-communication between MSC and T cell populations to realize full therapeutic effect. The application of these compartmental analysis can improve our understanding of MSC mechanism(s) of action and further lead to administration methods that deliver MSCs within a compartment for predictable potency.

PMID:
29717209
PMCID:
PMC5931547
DOI:
10.1038/s41598-018-24971-2
[Indexed for MEDLINE]
Free PMC Article

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