Cargando…

Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model

OBJECTIVE: We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor–β3 [TGF-β3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could b...

Descripción completa

Detalles Bibliográficos
Autores principales: Fisher, Matthew B., Belkin, Nicole S., Milby, Andrew H., Henning, Elizabeth A., Söegaard, Nicole, Kim, Minwook, Pfeifer, Christian, Saxena, Vishal, Dodge, George R., Burdick, Jason A., Schaer, Thomas P., Steinberg, David R., Mauck, Robert L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797244/
https://www.ncbi.nlm.nih.gov/pubmed/27047640
http://dx.doi.org/10.1177/1947603515623030
_version_ 1782421918252531712
author Fisher, Matthew B.
Belkin, Nicole S.
Milby, Andrew H.
Henning, Elizabeth A.
Söegaard, Nicole
Kim, Minwook
Pfeifer, Christian
Saxena, Vishal
Dodge, George R.
Burdick, Jason A.
Schaer, Thomas P.
Steinberg, David R.
Mauck, Robert L.
author_facet Fisher, Matthew B.
Belkin, Nicole S.
Milby, Andrew H.
Henning, Elizabeth A.
Söegaard, Nicole
Kim, Minwook
Pfeifer, Christian
Saxena, Vishal
Dodge, George R.
Burdick, Jason A.
Schaer, Thomas P.
Steinberg, David R.
Mauck, Robert L.
author_sort Fisher, Matthew B.
collection PubMed
description OBJECTIVE: We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor–β3 [TGF-β3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could be combined immediately prior to implantation to induce a superior healing response in vivo relative to the hydrogel alone. DESIGN: Trochlear chondral defects were created in Yucatan mini-pigs (6 months old). Treatment groups included an HA hydrogel alone and hydrogels containing allogeneic MSCs, TGF-β3, or both. Six weeks after surgery, micro-computed tomography was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. RESULTS: Treatment with TGF-β3 led to a marked increase in positive staining for collagen type II within defects (P < 0.05), while delivery of MSCs did not (P > 0.05). Neither condition had an impact on other histological semiquantitative scores (P > 0.05), and inclusion of MSCs led to significantly less defect fill (P < 0.05). For all measurements, no synergistic interaction was found between TGF-β3 and MSC treatment when they were delivered together (P > 0.05). CONCLUSIONS: At this early healing time point, treatment with TGF-β3 promoted the formation of collagen type II within the defect, while allogeneic MSCs had little benefit. Combination of TGF-β3 and MSCs at the time of surgery did not produce a synergistic effect. An in vitro precultured construct made of these components may be required to enhance in vivo repair in this model system.
format Online
Article
Text
id pubmed-4797244
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-47972442017-04-01 Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model Fisher, Matthew B. Belkin, Nicole S. Milby, Andrew H. Henning, Elizabeth A. Söegaard, Nicole Kim, Minwook Pfeifer, Christian Saxena, Vishal Dodge, George R. Burdick, Jason A. Schaer, Thomas P. Steinberg, David R. Mauck, Robert L. Cartilage Article OBJECTIVE: We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor–β3 [TGF-β3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could be combined immediately prior to implantation to induce a superior healing response in vivo relative to the hydrogel alone. DESIGN: Trochlear chondral defects were created in Yucatan mini-pigs (6 months old). Treatment groups included an HA hydrogel alone and hydrogels containing allogeneic MSCs, TGF-β3, or both. Six weeks after surgery, micro-computed tomography was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen. RESULTS: Treatment with TGF-β3 led to a marked increase in positive staining for collagen type II within defects (P < 0.05), while delivery of MSCs did not (P > 0.05). Neither condition had an impact on other histological semiquantitative scores (P > 0.05), and inclusion of MSCs led to significantly less defect fill (P < 0.05). For all measurements, no synergistic interaction was found between TGF-β3 and MSC treatment when they were delivered together (P > 0.05). CONCLUSIONS: At this early healing time point, treatment with TGF-β3 promoted the formation of collagen type II within the defect, while allogeneic MSCs had little benefit. Combination of TGF-β3 and MSCs at the time of surgery did not produce a synergistic effect. An in vitro precultured construct made of these components may be required to enhance in vivo repair in this model system. SAGE Publications 2015-12-28 2016-04 /pmc/articles/PMC4797244/ /pubmed/27047640 http://dx.doi.org/10.1177/1947603515623030 Text en © The Author(s) 2015
spellingShingle Article
Fisher, Matthew B.
Belkin, Nicole S.
Milby, Andrew H.
Henning, Elizabeth A.
Söegaard, Nicole
Kim, Minwook
Pfeifer, Christian
Saxena, Vishal
Dodge, George R.
Burdick, Jason A.
Schaer, Thomas P.
Steinberg, David R.
Mauck, Robert L.
Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model
title Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model
title_full Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model
title_fullStr Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model
title_full_unstemmed Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model
title_short Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage Repair in a Mini-Pig Model
title_sort effects of mesenchymal stem cell and growth factor delivery on cartilage repair in a mini-pig model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4797244/
https://www.ncbi.nlm.nih.gov/pubmed/27047640
http://dx.doi.org/10.1177/1947603515623030
work_keys_str_mv AT fishermatthewb effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT belkinnicoles effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT milbyandrewh effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT henningelizabetha effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT soegaardnicole effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT kimminwook effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT pfeiferchristian effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT saxenavishal effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT dodgegeorger effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT burdickjasona effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT schaerthomasp effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT steinbergdavidr effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel
AT mauckrobertl effectsofmesenchymalstemcellandgrowthfactordeliveryoncartilagerepairinaminipigmodel