title: Optimized delivery system achieves enhanced endomyocardial stem cell retention.
abstract: BACKGROUND
  Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention.
  
  
  RESULTS
  Stem cell retention was simulated in silico using 1- and 3-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol, a nickel and titanium alloy displaying shape memory and superelasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real-time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared with a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle without effect on biocompatibility or safety.
  
  
  CONCLUSIONS
  Modeling-guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention.
authors: From Division of Cardiovascular Diseases and Center for Regenerative Medicine, Mayo Clinic, Rochester, MN (A.B., R.J.C.-D., P.G.S., M.M.R., A.T.); Cardio3 BioSciences, Mont-Saint-Guibert, Belgium (J.-P.L., C.H., D.D., V.S., A.S.); and Cardiovascular Center, OLV Ziekenhuis, Aalst, Belgium (J.B.).
authors: Atta
authors: A
authors: Behfar
authors: Jean-Pierre
authors: JP
authors: Latere
authors: Jozef
authors: J
authors: Bartunek
authors: Christian
authors: C
authors: Homsy
authors: Dorothee
authors: D
authors: Daro
authors: Ruben J
authors: RJ
authors: Crespo-Diaz
authors: Paul G
authors: PG
authors: Stalboerger
authors: Valerie
authors: V
authors: Steenwinckel
authors: Aymeric
authors: A
authors: Seron
authors: Margaret M
authors: MM
authors: Redfield
authors: Andre
authors: A
authors: Terzic
mesh_terms: D000497:Alloys; D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D003198:Computer Simulation; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D004699:Endocardium / Q000166:cytology*; D004867:Equipment Design; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000628:therapy*; D009339:Needles; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000497:Alloys; C013616:nitinol
keywords: catheters; myocardial infarction; regeneration; stem cells