Stem cell therapy exhibits a threshold dependency rather than a dose response as typical for a pharmaceutical agent. The consequence is that treatments that deliver too few cells, as is common with cell selection and concentration technologies, may not provide a clinical benefit to the patient.

The traditional approach to overcome the threshold dose problem is to harvest cells from the patient which are then expanded by ex vivo cell culture. Expansion yields a larger number of cells, but completion of the culture process takes at least a few weeks which means that expanded cells are unavailable as a treatment option during the acute phase when cells exhibit their maximum therapeutic benefit. Culture processes are tightly regulated due to the inherent safety risks which results in a long path to market and a very expensive production process.

When stem cells are in a highly-stressed environment, as is seen immediately after an injury, they naturally enter the replicative phases of the cell cycle, and will continue cycling if the conditions are suitable. If the cells detect that the conditions are not appropriate they will return to quiescence or will undergo cell cycle arrest late in the G₁ phase. Rapid cell preparation techniques that are commercially available ignore the requirements for successful activation of mitosis through poor handling, imprudent use of anti-coagulants, and failure to control the ex vivo environment.

ActivCell is a highly engineered series of minimal manipulations that allow cells to begin self-replication prior to transplant by creating an biomimetic environment free of factors that inhibit natural biological processes. Cascia carefully controls all aspects of the ex vivo environment through deliberate and careful management of:

The process insures that the cells are not apoptotic and are still progressing through the cell cycle at the time of transplant. Administered into a carefully engineered microenvironment, the cells can continue replicating until migrating out of the delivery carrier and engrafting in the target tissue.  Each batch is customized to the patient's hematological and biochemical parameters which are rechecked at the time of preparation.

ActivCell achieves this result without the use of animal proteins or exogenous growth factors, the fundamental biologic properties of the cells are not altered, and no manipulations other than centrifugation and separation are performed. The entire process, from bone marrow aspiration to cell transplant, is accomplished during the course of a single surgery lasting just a few hours.

If expansion is needed, the cells can be cotransplanted with a small molecule pharmaceutical agent that prevents premature differentiation while allowing replication of stem cells to continue in the microenvironment.  Addition of this slow release agent is accomplished in a matter of seconds, thus allowing immediate implantation of the cells which are then free to expand at the site of transplant, obviating the need for a culture step.  This allows Cascia to deliver an expanded cell preparation during the acute phase of medical events such as heart attack or stroke.