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Modifying Stem Cells for Clinical Regenerative Applications
Technical Paper: Modifying Stem Cells for Clinical Regenerative Applications: A Practical Approach to a Fundamental Problem in Translational Research. Burrill Stem Cell Report, October 2007.

Rescue of Monocrotaline-Induced Pulmonary Arterial Hypertension
Publication: Rescue of Monocrotaline-Induced Pulmonary Arterial Hypertension Using Bone Marrow–Derived Endothelial-Like Progenitor Cells Efficacy of Combined Cell and eNOS Gene Therapy in Established Disease. Zhao et al. Circ Res. 2005;96:442-450.

Applications > Cell therapy > Regenerative Medicine

A variety of cell types, including stem cells, are being evaluated for the potential therapeutic regeneration of heart, bone, cartilage, nerve and other tissues. While unmodified cells may prove satisfactory in some applications, the ability to introduce a bioactive molecule, usually a gene construct or an mRNA, into the cell greatly increases the potential of the cell-based therapy. Cell modification can have a variety of affects including cell targeting, cell differentiation, angiogenesis, or regulation of specific cellular pathways such as suppression of an apoptotic pathway. Development of the means to modify cells prior to introduction into the patient relies on the ability to safely and consistently load cells with the bioactive molecule.

MaxCyte flow electroporation technology can load a wide range of biologically active molecules into a variety of primary cells and cell lines. It consistency loads cells without added chemical or biological reagents, using a closed and sterile processing assembly. This single system can expedite translation of regenerative applications from bench to commercialization by providing the necessary scalability while avoiding regulatory hurdles.


MaxCyte Flow Electroporation:
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Case Study: Pulmonary Arterial Hypertension (PAH)

Endothelial progenitor cells (EPC) have been intensively studied and are felt to have great potential for cardiovascular regenerative applications. PAH is a serious disorder of the pulmonary microvasculature with no satisfactory therapeutic approach. Stewart et al. at the University of Toronto, is developing a cell therapy in with autologous EPC are transfected, using MaxCyte Flow Electroporation, with a plasmid carrying full length cDNA encoding endothelial nitric oxide synthase (eNOS). A significant percentage of cells infused into a peripheral vein remain in the pulmonary vessels and secrete nitrous oxide (NO), a vasodilator and an angiogenic stimulant. Data from a rat model of the disease, induced by the administration of monocrotoline (MT), are shown in Figures 1 & 2.

Reversal of PAH in Rats using Engineered Cells
Figure 1. Reversal of PAH in Rats using Engineered Cells. Right ventricular systolic pressures (RVSP) measures pulmonary hypertension induced by MT. Twenty-one days post MT, rats are infused with either naïve cells or cells transfected with eNOS using the MaxCyte GT system. Difference in RVSP obvious at 35 days post MT. Survival is Increased by Engineered Cell Therapy
Figure 2. Survival is Increased by Engineered Cell Therapy. There is incremental improvement in survival with naïve cell infusion, and further increase in survival with infusion of cells engineered to express eNOS.