MENU
AUG 30, 2016 8:00 AM PDT

Immunomodulation and immunogenicity of human MSC-like cells : What did we learn from in vitro and in vivo studies ?

Speaker
  • Chairman, Institute for Med. Immunology & Berlin-Brandenburg Center for Regenerative Therapies (BCRT) & Dept. Immunology, Labor Berlin Vivantes, Charité GmbH Charité-Universitätsmedizin, Berl
    BIOGRAPHY

Abstract
Mesenchymal stromal cell (MSC) therapy is a promising option to support endogenous regeneration and immunomodulation. However, the clinical results are contradictory. We think that the recent studies have to major limitations: poor characterization of MSC(like) cell products which were used and the lack of adequate immune monitoring to better understand  therapy response, mode-of-action, dose-dependency etc.

Because of their high regenerative and immunomodulatory potency shown in various preclinical models and their well-defined manufactoring process in 3-D bioreactors, we focused on the characterization of placental-expanded mesenchymal like adherent cells (PLX) that are aimed to be applied as allogeneic off-the-shelf product.

Interestingly, by minor manipulation in the manufactoring process, Pluristem generated two related products PLX-PAD and PLX-RAD. Both PLX-cell types were comparable regarding their in vitro differentiation capacity and marker profile (CD73+90+105+45-31-34-) that is typical for MSC-like cells. However, the cells showed different properties in some but not all preclinical models. We hypothesized that the protective effects are mediated by the PLX-cells´ secretome which might be different between PLX-RAD and PLX-PAD cells.  In fact, conditioned medium of PLX-RAD expressed a distinct secretome and showed distinct effects in vitro and in vivo. Whole genome DNA methylation analysis and CD screen revealed significant differences between the two products.

PLX-PAD cells are supportive in different tissue regeneration models. In fact, clinical phase I/IIa studies in severe chronic limb ischemia (CLI) and muscle injury demonstrated safety but also clear hints for efficacy. Immune monitoring gave insights into immunogenicity, immune modulation, and dose-related effects which help to design ongoing studies.

In summary, extensive biomarker studies provided mechanistic insights into PLX products and highlighted the need for careful characterization of MSC-like cell products to better understand dosing, indication, mode-of-action etc.

Show Resources
You May Also Like
SEP 14, 2021 7:00 AM PDT
C.E. CREDITS
SEP 14, 2021 7:00 AM PDT
Date: September 14, 2021 Time: 7am PDT, 10am EDT, 4pm CEST A conventional thermal cycler has long been a commodity product in the lab and end-point PCR techniques can be completed almost wit...
OCT 20, 2021 10:00 AM PDT
C.E. CREDITS
OCT 20, 2021 10:00 AM PDT
Date: October 20, 2021 Time:10:00am (PDT), 1:00pm (EDT) As the prevalence of Diabetes continues to rise in many areas across the globe, healthcare providers continue to look for methods that...
JUN 09, 2021 7:00 AM PDT
C.E. CREDITS
JUN 09, 2021 7:00 AM PDT
Date: June 9, 2021 Time: 09 June 2021, 7am PDT, 10am EDT, 4pm CEST cells with dramatic implications on the validity of past cell culture related research. The fact that at least 509 cell lin...
SEP 29, 2021 11:00 AM PDT
C.E. CREDITS
SEP 29, 2021 11:00 AM PDT
Date: Septembr 29, 2021 Time: 11:00am (PDT), 2:00pm (EDT) 3D cell models are becoming increasingly popular for studying complex biological effects, tissue functionality, and diseases. While...
JUN 03, 2021 12:00 PM CST
JUN 03, 2021 12:00 PM CST
DATE: June 3, 2021 TIME: 12:00pm SGT This webinar is a virtual event that focuses on utilizing the Gibco CTS Rotea System for Cell and Gene Therapy...
NOV 30, 2021 11:00 AM PST
C.E. CREDITS
NOV 30, 2021 11:00 AM PST
Date: November 30, 2021 Time: 11:00am (PDT), 2:00pm (EDT) In the recent years, measurable residual disease (MRD) assessment on multiple myeloma patients has gained increasing relevance. After...
Loading Comments...
Show Resources