Fused X-ray and MR Imaging Guidance of Intrapericardial Delivery of Microencapsulated Human Mesenchymal Stem Cells in Immunocompetent Swine

Abstract

Purpose To assess intrapericardial delivery of microencapsulated, xenogeneic human mesenchymal stem cells (hMSCs) by using x-ray fused with magnetic resonance (MR) imaging (x-ray/MR imaging) guidance as a potential treatment for ischemic cardiovascular disease in an immunocompetent swine model. Materials and Methods All animal experiments were approved by the institutional animal care and use committee. Stem cell microencapsulation was performed by using a modified alginate-poly-l-lysine-alginate encapsulation method to include 10% (wt/vol) barium sulfate to create barium-alginate microcapsules (BaCaps) that contained hMSCs. With x-ray/MR imaging guidance, eight female pigs (approximately 25 kg) were randomized to receive either BaCaps with hMSCs, empty BaCaps, naked hMSCs, or saline by using a percutaneous subxiphoid approach and were compared with animals that received empty BaCaps (n = 1) or BaCaps with hMSCs (n = 2) by using standard fluoroscopic delivery only. MR images and C-arm computed tomographic (CT) images were acquired before injection and 1 week after delivery. Animals were sacrificed immediately or at 1 week for histopathologic validation. Cardiac function between baseline and 1 week after delivery was evaluated by using a paired Student t test. Results hMSCs remained highly viable (94.8% ± 6) 2 days after encapsulation in vitro. With x-ray/MR imaging, successful intrapericardial access and delivery were achieved in all animals. BaCaps were visible fluoroscopically and at C-arm CT immediately and 1 week after delivery. Whereas BaCaps were free floating immediately after delivery, they consolidated into a pseudoepicardial tissue patch at 1 week, with hMSCs remaining highly viable within BaCaps; naked hMSCs were poorly retained. Follow-up imaging 1 week after x-ray/MR imaging–guided intrapericardial delivery showed no evidence of pericardial adhesion and/or effusion or adverse effect on cardiac function. In contradistinction, BaCaps delivery with xray fluoroscopy without x-ray/MR imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1 week. Conclusion Intrapericardial delivery of BaCaps with hMSCs leads to high cell retention and survival. With x-ray/MR imaging guidance, intrapericardial delivery can be performed safely in the absence of preexisting pericardial effusion to provide a novel route for cardiac cellular regenerative therapy.

Injection of ROS‐Responsive Hydrogel Loaded with Basic Fibroblast Growth Factor into the Pericardial Cavity for Heart Repair

“…Direct injection into the pericardial cavity (i.e., intrapericardial injection or iPC injection) has been employed to deliver stem cells, exosomes, or growth factors in a non‐hydrogel Gelfoam or saline for experimental cardiac repair. [ 20,21 ]…”

Emerging Imaging Modalities in Regenerative Medicine

“…Additionally, nanoparticles can be formulated to contain materials capable of generating high levels of contrast that would otherwise not be attainable with small molecules such as iodine [ 37 , 38 ]. CT technology for tracking of transplanted cells in vivo continues to experience challenges due to poor sensitivity of CT and complications associated with contrast loading of transplanted cells; however, pre-clinical efforts are continuing to evolve and show potential for clinical application [ 39 – 41 ].…”

Noninvasive Monitoring of Allogeneic Stem Cell Delivery with Dual-Modality Imaging-Visible Microcapsules in a Rabbit Model of Peripheral Arterial Disease

“…By converting direct cell labeling into microcapsule labeling, high payload of contrast agents, which would normally be cytotoxic, can now be used to enable cell tracking with high sensitivity [47]. We have previously demonstrated the feasibility of applying barium sulfate-impregnated microcapsules for X-ray monitoring of MSC delivery in PAD rabbits [15] and immunocompetent swine [23]. However, the potential toxicity related to heavy metal raises concerns for clinical translation.…”

“…MSC microencapsulation was performed using an electrostatic droplet generator as previously described [23–25]. Prior to encapsulation, PFOB was emulsified with an equal volume of lecithin (Sigma, St. Louis, MO) to make a homogenous stable solution.…”