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Strategies to Advance Stem Cell Therapy from Bench to Bedside

Jan 14, 2015 1:00:25 PM / by Maria

Stem cell therapy has required decades of inquiry to determine how to sustain and propagate stem cells in the lab. What key factors should be considered?

Stem cell therapy technology holds great promise for curing many diseases.  Previously we discussed some of the challenges facing this emerging technology.  Now we discuss strategies to increase the efficiency of stem cell therapy to move these therapies into the clinic faster.[1]

Co-administration and Pre-conditioning

As mentioned in part 1 of this series, stem cells are highly dependent upon interactions with other cells and their environment.  As such, co-administration and pre-conditioning can contribute to the success of the therapy from many angles.  In terms of preparation and delivery of the stem cell therapy, pre-conditioning or treatment of the cells before harvesting cells and delivery of the cells can be beneficial.  Often times this may run in parallel with pharmacological treatment.  A variety of treatment paradigms have shown improved efficacy with combinations of multiple cell types, genetically engineered cells, or even progenitor cells with specific growth factors and cytokines. The game plan is finding the right combination to prepare the cells and then deliver them effectively to the right tissue.

Dose and Duration Stem Cell Therapy Treatment Options

For any given chemical entity a dose response curve demonstrating a measurable outcome can guide the dosing and timing for patient treatment.  Stem cell therapy has not proved as predictable. Each patient receiving stem cell therapy could be considered a study of one. There are rough guidelines on how many cells are effective for a single treatment. For example, in a study on multiple sclerosis, patients received 30 – 50 million MSCs per kilogram of bone marrow derived mesenchymal stem cells. But in a spinal cord injury clinical trial, patients received 5 – 6 million MSCs per kilogram of the same type of cells.  Why the difference? Major considerations include inflammation response and graft versus host disease in allogeneic transplants. While higher numbers might seem more effective, akin to drug studies, we are finding there is a sweet spot for the right dose. In contrast to targeted delivery, a systemic approach may be warranted in many cases.

Autologous vs Allogeneic Stem Cell Therapy Decisions

Stem Cell Therapy Moving Stem Cell Therapy from Bench to Bedside Requires Precise Strategies 1

A major consideration is whether the cells used will be derived from the patient or from a donor. Allogeneic cells have primarily been used in the past, as it has been difficult to obtain sufficient numbers of ideal cells from the patient for use.  Allogeneic cells offer serveral advantages at this time, including the ability to develop “ready-to-use” therapies that have been developed using GMP standards with consistent reliable outcomes.  However, overcoming graft versus host problems is not a minor consideration.  As technologies improve, the ability to obtain cells directly from the patient for manipulation and therapy are likely to increase.

Next, we discuss what lessons can be learned from drug discovery pipelines in developing stem cell therapy treatments.

Reference

  1. Srijaya, T.C. et al. (2014) Advancing stem cell therapy from bench to bedside: lessons from drug therapies. Journal of Translational Medicine, 12:243

Topics: Cell Therapy, Regenerative Medicine, Stem Cell Therapy, stem cell transplantation, Stem Cells, Basic Research

Maria

Written by Maria

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