Encapsulation of factor IX–engineered mesenchymal stem cells in fibrinogen–alginate microcapsules enhances their viability and transgene secretion

Abstract

Cell microencapsulation holds significant promise as a strategy for cellular therapies; however, inadequate survival and functionality of the enclosed cells limit its application in hemophilia treatment. Here, we evaluated the use of alginate-based microcapsules to enhance the viability and transgene secretion of human cord blood–derived mesenchymal stem cells in three-dimensional cultures. Given the positive effects of extracellular matrix molecules on mesenchymal stem cell growth, we tested whether fibrinogen-supplemented alginate microcapsules can improve the efficiency of encapsulated factor IX–engineered mesenchymal stem cells as a treatment of hemophilia B. We found that fibrinogen-supplemented alginate microcapsules (a) significantly enhanced the viability and proliferation of factor IX–engineered mesenchymal stem cells and (b) increased factor IX secretion by mesenchymal stem cells compared to mesenchymal stem cells in nonsupplemented microcapsules. Moreover, we observed the osteogenic, but not chondrogenic or adipogenic, differentiation capability of factor IX–engineered cord blood mesenchymal stem cells and their efficient factor IX secretion while encapsulated in fibrinogen-supplemented alginate microcapsules. Thus, the use of engineered mesenchymal stem cells encapsulated in fibrinogen-modified microcapsules may have potential application in the treatment of hemophilia or other protein deficiency diseases.

Microcapsules engineered to support mesenchymal stem cell (MSC) survival and proliferation enable long-term retention of MSCs in infarcted myocardium

“…Similar proliferation rates have been observed with a collagen matrix [51]. In addition, proliferation of MSCs in microcapsules has generally not been observed in earlier approaches [31,45]. Transplanted MSCs perform all functions that are reported to contribute to tissue repair, as they are able to differentiate into other lineages and secrete paracrine factors.…”

“…All components are critical for the optimal performance of the microcapsule supporting proliferation and long-term survival of MSCs. Although materials such as agarose (or substituted by alginate) in combination with collagen [44], fibrin and fibronectin [30,31,45] have been investigated before, the resulting microcapsule biomaterials in earlier studies had limited performance. Most encapsulated cells (MSCs or fibroblasts) had a decreased viability over time.…”

Utilizing Core–Shell Fibrous Collagen-Alginate Hydrogel Cell Delivery System for Bone Tissue Engineering

“…Hydrogel biopolymers such as collagen, alginate, and chitosan have shown cellular compatibility and the capacity to load and carry cells to the target tissues. [5][6][7][8] Collagen can load cells and has good 1 biocompatibility, while maintaining cellular functions that mimic the native three-dimensional (3D) tissue environment. 9 Collagen also becomes a gel when pH, ionic concentration, and temperature are modulated to near biological conditions.…”

Stem Cell-Based Therapies for Cancer

“…In past studies, sECM acted as the necessary biomechanical substrate for endogenous neuroregeneration in models of intracerebral hypoxia-ischemia and traumatic spinal cord injury, by increasing their stem cell viability and promoting differentiation into neurons (Pan, Ren, Cui, & Xu, 2009;Park, Teng, & Snyder, 2002;Teng et al, 2002). Recently, it was discovered that MSCs encapsulated in fibrinogen-alginate microcapsules possessed a significantly increased survival as compared to unencapsulated cells (Sayyar et al, 2012). In another recent study, Reagan et al demonstrated the utility of a scaffold-based delivery system for sustained therapeutic MSCs release and their ability to express genetically introduced therapeutic TRAIL.…”