Developing a new stem cell therapy for immune disorders

Investigators: Prof. Reuven Or and Dr Osnat Hazan, Hadassah Hebrew Uni Hospital, Jerusalem

The Medical Problem: A variety of pathological conditions arise as a result of immune system dysregulation. For example, in autoimmune diseases, Graft versus Host Disease (GVHD) (a medical complication commonly associated with bone marrow transplantation) and rejection of transplanted organs, increased activity of the immune system causes damage of bodily/transplanted tissues. Unfortunately, in many cases the currently available therapies are unable to restore normal immune system function.  Therefore, there is a need for developing new therapies that can enhance the control of the immune system.

Background Research: Mesenchymal stem cells (MSCs) are multipotentstromal (connective tissue) cells that can differentiate into a variety of cell types. Over the past decade, the immunomodulatory functionsof MSCs have sparked great interest in their application towards treatment of various immune disorders. The advantage of cell therapy is its ability to concomitantly activate multiple restorative pathways through cell-based release of multiple factors.

The researchers are conducting two studiesthat aim to contribute knowledge to improving cell therapy for immune disorders.

Study 1
Professor Or has established an immune-regulatory triple combination treatment (TCT) for MSCs to improve the outcome of MSCs immune cell therapy. The improved regulatory function of TCT MSCs has been provenin vitro (murine and human cells) and in vivo in a GVHD mice model. These results were published in Stem Cells Journal (2015;33:2256–2267).

Theaim of Study 1is to examine the efficacy of in vivo TCT MSCs therapy in two models for immune disorder —an allogeneic skin graft model and a model for multiple sclerosis. The research plan involves testing the effect of TCT MSCs on rejection/ disease progression, respectively.

Study 2
Professor Or’s team and others have shown that bone marrow mesenchymal stem cells (bmMSC) can excrete exosomes (these are small cell structures that share the same orientation of their membrane as the cell). Prof. Or hypothesizes that bmMSC may at least partly induce their immune-regulatory effects through exosome secretion.

The aim of Study 2 is to evaluate the contribution of Leukemia Inhibitory Factor (LIF) treatment(a treatment typically added to stem cell culture medium to reduce spontaneous differentiation)

on bmMSC exosome inhibition of lymphocyte activation (this is increased activity of the immune system).

Contribution of the project to finding a treatment: The cumulative data from the two studies will contribute knowledge to improving cell therapy for immune disorders and facilitate adaptation of human TCT MSCs for clinical trials.