title: In Situ Transplantation of Alginate Bioencapsulated Adipose Tissues Derived Stem Cells (ADSCs) via Hepatic Injection in a Mouse Model.
abstract: OBJECTIVE
  Adipose tissue derived stem cells (ADSCs) transplantation has recently gained widespread enthusiasm, particularly in the perspective to use them as potential alternative cell sources for hepatocytes in cell based therapy, mainly because of their capability of hepatogenic differentiation in vitro and in vivo. But some challenges remain to be addressed, including whether ADSCs can be provided effectively to the target organ and whether subsequent proliferation of transplanted cells can be achieved. To date, intrasplenic injection is the conventional method to deliver ADSCs into the liver; however, a number of donor cells retained in the spleen has been reported. In this study, our objective is to evaluate a novel route to transplant ADSCs specifically to the liver. We aimed to test the feasibility of in situ transplantation of ADSCs by injecting bioencapsulated ADSCs into the liver in mouse model.
  
  
  METHODS
  The ADSCs isolated from human alpha 1 antitrypsin (M-hAAT) transgenic mice were used to allow delivered ADSCs be readily identified in the liver of recipient mice, and alginate was selected as a cell carrier. We first evaluated whether alginate microspheres are implantable into the liver tissue by injection and whether ADSCs could migrate from alginate microspheres (study one). Once proven, we then examined the in vivo fate of ADSCs loaded microspheres in the liver. Specifically, we evaluated whether transplanted, undifferentiated ASDCs could be induced by the local microenvironment toward hepatogenic differentiation and the distribution of surviving ADSCs in major tissue organs (study two).
  
  
  RESULTS
  Our results indicated ADSCs loaded alginate microspheres were implantable into the liver. Both degraded and residual alginate microspheres were observed in the liver up to three weeks. The viable ADSCs were detectable surrounding degraded and residual alginate microspheres in the liver and other major organs such as bone marrow and the lungs. Importantly, transplanted ADSCs underwent hepatogenic differentiation to become cells expressing albumin in the liver. These findings improve our understanding of the interplay between ADSCs (donor cells), alginate (biomaterial), and local microenvironment in a hepatectomized mouse model, and might improve the strategy of in situ transplantation of ADSCs in treating liver diseases.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Mong-Jen
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Simpson
authors.affiliation: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Beveridge
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Elshikha
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Mohammad Ahsanul
authors.initials: MA
authors.lastname: Akbar
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Hsin-Yin
authors.initials: HY
authors.lastname: Tsai
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hinske
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Junling
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Grunwitz
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Tina
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Brantly
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Sihong
authors.initials: S
authors.lastname: Song
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002214:Capsules; D002454:Cell Differentiation; D005240:Feasibility Studies; D020723:Glucuronic Acid / Q000737:chemistry; D022781:Hepatocytes / Q000166:cytology; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007267:Injections; D008099:Liver / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008863:Microspheres; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000737:chemistry* / Q000166:cytology*; D000515:alpha 1-Antitrypsin / Q000235:genetics
chemical_list: D000464:Alginates; D002214:Capsules; D006603:Hexuronic Acids; D000515:alpha 1-Antitrypsin; D020723:Glucuronic Acid