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Therapeutic Delivery Specifications Identified Through Compartmental Analysis of a Mesenchymal Stromal Cell-Immune Reaction.
Li, Matthew; Khong, Danika; Chin, Ling-Yee; Singleton, Amy; Parekkadan, Biju.
Afiliação
  • Li M; 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.
  • Khong D; 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.
  • Chin LY; 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.
  • Singleton A; 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.
  • Parekkadan B; 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.
Sci Rep ; 8(1): 6816, 2018 05 01.
Article em En | MEDLINE | ID: mdl-29717209
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Linfócitos T / Terapia de Imunossupressão / Transplante de Células-Tronco Mesenquimais / Nicho de Células-Tronco / Células-Tronco Mesenquimais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Monócitos / Linfócitos T / Terapia de Imunossupressão / Transplante de Células-Tronco Mesenquimais / Nicho de Células-Tronco / Células-Tronco Mesenquimais Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Sci Rep Ano de publicação: 2018 Tipo de documento: Article