Cell-Based Therapies

3/19/2012 7:42:33 AM #

There is an urgent need to develop in vitro assays that can predict the effect of a given MSC-based product whether autologous or allogeneic on the patient's immune responses. First, MSC-based products need to be more standardized and uniform and an accurate account of live vs. dead cells delivered must be measured. We also need to determine the host immune response to the MSC-based therapy. There have been many assumptions but no detailed studies. Should we immunotype MSCs and/or measure MHC compatibilities--i.e.--do MSC donors from certain immune phenotypes achieve better therapeutic effects in all types of hosts or just some? Can we use similar criteria to organ transplant matching for MSC-therapies to ensure greater therapeutic effect?  Perhaps one in vitro assay can be co-culture of the MSC-products with PBMCs from a gamut of MHC II donors and the subsequent effect on cell surface expression of the MSC's MHC receptors and cytokine/chemokine expression measured? We should not just assume that these cells are "immunopriviledged" but we should identify the exact responses that the MSC-therapy has on host immune responses. There is a lot to be learned from their therapeutic effects.

Aline M. Betancourt, PhD | Reply

3/20/2012 6:28:54 AM #

I believe that the most effective cell-based therapies will come about from interdisciplinary, multivariate approaches where all niche components, e.g. matrix, growth factors, cells, etc., are provided in developmental (for embryonic stem cells) or biologically (for adult stem cells) appropriate ways to correctly guide regeneration. The most successful attempts to date have involved biomimicry on many levels, and proposals/RFA focusing on transformative but interdisciplinary efforts (say pairing engineers, biologists, clinicians, etc) are the mostly likely applications to have that aspect.

Adam Engler | Reply

3/20/2012 10:13:46 AM #

I am a physician-scientist actively engaged in fundamental science of hematopoietic stem/progenitor cells and clinical research of these cells in a variety of diseases including cancer, ischemic heart disease, vascular disease, diabetes mellitus, graft-versus-host disease and Crohn's disease.

Here are some of the major knowledge gaps and unmet needs that I perceive:
* Use of autologous cell therapies makes it difficult to ascertain mechanisms of injected cells and cell fate. Thus better labeling and tracking technologies are needed.
* Cell processing among trials is varied and may explain discrepancies. There needs to be better description of cell separation techniques, transparency in the details and direct comparisons so that the research community can determine to what extent the cell separation/selection techniques influence clinical outcomes. Otherwise, hasty decisions about a particular cell therapy affecting a certain disease could be made.
* Better description of cell phenotype and function should be reported among clinical cell therapy trials so that the community can understand the "test agent." Most clinical cell therapy trials put heavier emphasis on reporting patient characteristics. Whereas, these Table 1 data are very important, there should be equal or greater description of the injected/applied cells.

Christopher R. Cogle, M.D. | Reply