title: Fused X-ray and MR imaging guidance of intrapericardial delivery of microencapsulated human mesenchymal stem cells in immunocompetent swine.
abstract: OBJECTIVE
  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.
  
  
  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 x-ray fluoroscopy without x-ray/MR imaging (n = 3) resulted in pericardial adhesions and poor hMSC viability after 1 week.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Division of MR Research, Russell H. Morgan Department of Radiology and Radiological Science (Y.F., C.R.W., J.W.M.B., M.S., D.L.K.), Department of Molecular and Comparative Pathobiology (N.A., K.G., D.L.K.), Institute for Cell Engineering (J.W.M.B.), and Division of Cardiology, Department of Internal Medicine (P.V.J.), The Johns Hopkins University School of Medicine, 600 N Wolfe St, 314 Park Bldg, Baltimore, MD 21087; and Department of Corporate Technology, Siemens Corporation, Baltimore, Md (T.E., A.F., W.D.G.).
authors.forename: Yingli
authors.initials: Y
authors.lastname: Fu
authors.forename: Nicole
authors.initials: N
authors.lastname: Azene
authors.forename: Tina
authors.initials: T
authors.lastname: Ehtiati
authors.forename: Aaron
authors.initials: A
authors.lastname: Flammang
authors.forename: Wesley D
authors.initials: WD
authors.lastname: Gilson
authors.forename: Kathleen
authors.initials: K
authors.lastname: Gabrielson
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Weiss
authors.forename: Jeff W M
authors.initials: JW
authors.lastname: Bulte
authors.forename: Meiyappan
authors.initials: M
authors.lastname: Solaiyappan
authors.forename: Peter V
authors.initials: PV
authors.lastname: Johnston
authors.forename: Dara L
authors.initials: DL
authors.lastname: Kraitchman
mesh_terms: D000818:Animals; D003327:Coronary Disease / Q000628:therapy*; D005240:Feasibility Studies; D005260:Female; D005471:Fluoroscopy; D006801:Humans; D021621:Imaging, Three-Dimensional; D053783:Magnetic Resonance Imaging, Interventional / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D023421:Models, Animal; D064847:Multimodal Imaging / Q000379:methods*; D010496:Pericardium; D015641:Radiography, Interventional; D015203:Reproducibility of Results; D013552:Swine
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