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Using CD34+ Cells to Stimulate Vascularization and Inhibit Encapsulation of Implantable Bioartificial Devices

For successful engraftment of allogenic cells using a bioartificial device, the device must immunoisolate cells, be immuno‐invisible, exhibit good bulk transport characteristics, and be rapidly vascularized. Current devices are not vascularized quickly enough to maintain adequate cell viability and bulk transport, and device encapsulation is problematic. To address these issues, we tested devices consisting of a proangiogenic scaffold surrounding a cell‐encapsulating alginate core in mice. Our goal was to prevent device encapsulation while stimulating vascularization. We found that despite their proangiogenic nature, the scaffolds acted as a physical barrier, inhibiting the approach of vessels to the alginate core. We also examined the ability of CD34+ peripheral blood cells to induce vessel formation in the devices, and found that they stimulated capillary growth proximate to the device and reduced encapsulation. (CD34+ cells promote vascular growth in diabetic mice.) Because CD34+ cells from some patients are dysfunctional, clinically, it may be beneficial to use allogenic CD34+ cells. Thus, we immunesuppressed mice prior to device implantation and CD34+ cell injection. Surprisingly, immunesuppression, inhibited vessel growth and increased encapsulation. Thus, CD34+ cells may help create an optimal milieu for device implantation.