rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model

Ana Rey-Rico,1 Jagadeesh K Venkatesan,1 Gertrud Schmitt,1 Angel Concheiro,2 Henning Madry,1,3 Carmen Alvarez-Lorenzo,2 Magali Cucchiarini1 1Center of Experimental Orthopedics, Saarland University Medical Center, Homburg, Germany; 2Department of Pharmacology, Pharmacy and Pharmaceutical Technology,...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Rey-Rico A, Venkatesan JK, Schmitt G, Concheiro A, Madry H, Alvarez-Lorenzo C, Cucchiarini M
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2017
Materias:
Acceso en línea:https://doaj.org/article/6a67142a90284a1d95957030f0050421
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:6a67142a90284a1d95957030f0050421
record_format dspace
spelling oai:doaj.org-article:6a67142a90284a1d95957030f00504212021-12-02T02:41:16ZrAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model1178-2013https://doaj.org/article/6a67142a90284a1d95957030f00504212017-09-01T00:00:00Zhttps://www.dovepress.com/raav-mediated-overexpression-of-tgf-beta-via-vector-delivery-in-polyme-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ana Rey-Rico,1 Jagadeesh K Venkatesan,1 Gertrud Schmitt,1 Angel Concheiro,2 Henning Madry,1,3 Carmen Alvarez-Lorenzo,2 Magali Cucchiarini1 1Center of Experimental Orthopedics, Saarland University Medical Center, Homburg, Germany; 2Department of Pharmacology, Pharmacy and Pharmaceutical Technology, R+ DPharma Group (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; 3Department of Orthopedics and Orthopedic Surgery, Saarland University Medical Center, Homburg, Germany Abstract: Recombinant adeno-associated virus (rAAV) vectors are clinically adapted vectors to durably treat human osteoarthritis (OA). Controlled delivery of rAAV vectors via polymeric micelles was reported to enhance the temporal and spatial presentation of the vectors into their targets. Here, we tested the feasibility of delivering rAAV vectors via poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO) (poloxamer and poloxamine) polymeric micelles as a means to overexpress the therapeutic factor transforming growth factor-beta (TGF-β) in human OA chondrocytes and in experimental human osteochondral defects. Application of rAAV-human transforming growth factor-beta using such micelles increased the levels of TGF-β transgene expression compared with free vector treatment. Overexpression of TGF-β with these systems resulted in higher proteoglycan deposition and increased cell numbers in OA chondrocytes. In osteochondral defect cultures, a higher deposition of type-II collagen and reduced hypertrophic events were noted. Delivery of therapeutic rAAV vectors via PEO-PPO-PEO micelles may provide potential tools to remodel human OA cartilage. Keywords: controlled delivery, human articular cartilage, rAAV gene transfer, TGF-β, poloxamer, poloxamineRey-Rico AVenkatesan JKSchmitt GConcheiro AMadry HAlvarez-Lorenzo CCucchiarini MDove Medical Pressarticlehuman articular cartilagerAAV gene transferTGF-poloxamerpoloxamine.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 6985-6996 (2017)
institution DOAJ
collection DOAJ
language EN
topic human articular cartilage
rAAV gene transfer
TGF-
poloxamer
poloxamine.
Medicine (General)
R5-920
spellingShingle human articular cartilage
rAAV gene transfer
TGF-
poloxamer
poloxamine.
Medicine (General)
R5-920
Rey-Rico A
Venkatesan JK
Schmitt G
Concheiro A
Madry H
Alvarez-Lorenzo C
Cucchiarini M
rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model
description Ana Rey-Rico,1 Jagadeesh K Venkatesan,1 Gertrud Schmitt,1 Angel Concheiro,2 Henning Madry,1,3 Carmen Alvarez-Lorenzo,2 Magali Cucchiarini1 1Center of Experimental Orthopedics, Saarland University Medical Center, Homburg, Germany; 2Department of Pharmacology, Pharmacy and Pharmaceutical Technology, R+ DPharma Group (GI-1645), Facultad de Farmacia and Health Research Institute of Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain; 3Department of Orthopedics and Orthopedic Surgery, Saarland University Medical Center, Homburg, Germany Abstract: Recombinant adeno-associated virus (rAAV) vectors are clinically adapted vectors to durably treat human osteoarthritis (OA). Controlled delivery of rAAV vectors via polymeric micelles was reported to enhance the temporal and spatial presentation of the vectors into their targets. Here, we tested the feasibility of delivering rAAV vectors via poly (ethylene oxide) (PEO) and poly (propylene oxide) (PPO) (poloxamer and poloxamine) polymeric micelles as a means to overexpress the therapeutic factor transforming growth factor-beta (TGF-β) in human OA chondrocytes and in experimental human osteochondral defects. Application of rAAV-human transforming growth factor-beta using such micelles increased the levels of TGF-β transgene expression compared with free vector treatment. Overexpression of TGF-β with these systems resulted in higher proteoglycan deposition and increased cell numbers in OA chondrocytes. In osteochondral defect cultures, a higher deposition of type-II collagen and reduced hypertrophic events were noted. Delivery of therapeutic rAAV vectors via PEO-PPO-PEO micelles may provide potential tools to remodel human OA cartilage. Keywords: controlled delivery, human articular cartilage, rAAV gene transfer, TGF-β, poloxamer, poloxamine
format article
author Rey-Rico A
Venkatesan JK
Schmitt G
Concheiro A
Madry H
Alvarez-Lorenzo C
Cucchiarini M
author_facet Rey-Rico A
Venkatesan JK
Schmitt G
Concheiro A
Madry H
Alvarez-Lorenzo C
Cucchiarini M
author_sort Rey-Rico A
title rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model
title_short rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model
title_full rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model
title_fullStr rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model
title_full_unstemmed rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model
title_sort raav-mediated overexpression of tgf-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/6a67142a90284a1d95957030f0050421
work_keys_str_mv AT reyricoa raavmediatedoverexpressionoftgfbetanbspviavectordeliveryinpolymericmicellesstimulatesthebiologicalandreparativeactivitiesofhumanarticularchondrocytesinvitroandinahumanosteochondraldefectmodel
AT venkatesanjk raavmediatedoverexpressionoftgfbetanbspviavectordeliveryinpolymericmicellesstimulatesthebiologicalandreparativeactivitiesofhumanarticularchondrocytesinvitroandinahumanosteochondraldefectmodel
AT schmittg raavmediatedoverexpressionoftgfbetanbspviavectordeliveryinpolymericmicellesstimulatesthebiologicalandreparativeactivitiesofhumanarticularchondrocytesinvitroandinahumanosteochondraldefectmodel
AT concheiroa raavmediatedoverexpressionoftgfbetanbspviavectordeliveryinpolymericmicellesstimulatesthebiologicalandreparativeactivitiesofhumanarticularchondrocytesinvitroandinahumanosteochondraldefectmodel
AT madryh raavmediatedoverexpressionoftgfbetanbspviavectordeliveryinpolymericmicellesstimulatesthebiologicalandreparativeactivitiesofhumanarticularchondrocytesinvitroandinahumanosteochondraldefectmodel
AT alvarezlorenzoc raavmediatedoverexpressionoftgfbetanbspviavectordeliveryinpolymericmicellesstimulatesthebiologicalandreparativeactivitiesofhumanarticularchondrocytesinvitroandinahumanosteochondraldefectmodel
AT cucchiarinim raavmediatedoverexpressionoftgfbetanbspviavectordeliveryinpolymericmicellesstimulatesthebiologicalandreparativeactivitiesofhumanarticularchondrocytesinvitroandinahumanosteochondraldefectmodel
_version_ 1718402292271546368