TY - JOUR
T1 - Hyperosmolarity and hypoxia induce chondrogenesis of adipose-derived stem cells in a collagen type 2 hydrogel
AU - Jurgens, Wouter J.F.M.
AU - Lu, Zufu
AU - Zandieh-Doulabi, Behrouz
AU - Kuik, Dirk J.
AU - Ritt, Marco J.P.F.
AU - Helder, Marco N.
PY - 2012/7
Y1 - 2012/7
N2 - Apart from soluble growth factors, various other biophysicochemical cues are known to promote chondrogenesis. Under physiological conditions, cartilage in the joint comprises a hyperosmotic and hypoxic environment. Therefore, in this study, we examined the inductive effects of hyperosmotic and/or hypoxic conditions on adipose stem cells (ASCs) and compared them with conventional TGFβ1-induction. After encapsulation in collagen type II hydrogels and specific induction, ASCs were assessed for viability, proliferation, morphology and chondrogenic differentiation potential. Viability was similar under all conditions, with low proliferative activity. After 4days, hypoxia and/or hyperosmolarity did not affect round cell morphology, while cells were mainly stretched in the TGFβ1-induced group. At 21days, the TGFß1-treated group had aggregated into a cell nodule. Hyperosmolarity mimicked this aggregation to a lesser extent, whereas cells under hypoxia stretched out after 21days, with a combined effect in the hypoxic/hyperosmotic group. Both individual and combined hyperosmotic and/or hypoxic conditions significantly upregulated SOX5, SOX9, COMP and Link-p gene expression compared with the non-induced group, and to similar levels as the TGFβ1-induced group. GAG synthesis in both hydrogel and medium was increased under hypoxic conditions, whereas hyperosmolarity decreased GAG formation in the hydrogels, but increased GAG formation in the medium. We conclude that in a joint mimicking the three-dimensional (3D) micro-environment, a combination of hyperosmolarity and hypoxia is able to induce chondrogenesis to the same extent as TGFβ1. This might lead to an interesting alternative when considering short-term triggering in a one-step surgical procedure for the treatment of cartilaginous defects.
AB - Apart from soluble growth factors, various other biophysicochemical cues are known to promote chondrogenesis. Under physiological conditions, cartilage in the joint comprises a hyperosmotic and hypoxic environment. Therefore, in this study, we examined the inductive effects of hyperosmotic and/or hypoxic conditions on adipose stem cells (ASCs) and compared them with conventional TGFβ1-induction. After encapsulation in collagen type II hydrogels and specific induction, ASCs were assessed for viability, proliferation, morphology and chondrogenic differentiation potential. Viability was similar under all conditions, with low proliferative activity. After 4days, hypoxia and/or hyperosmolarity did not affect round cell morphology, while cells were mainly stretched in the TGFβ1-induced group. At 21days, the TGFß1-treated group had aggregated into a cell nodule. Hyperosmolarity mimicked this aggregation to a lesser extent, whereas cells under hypoxia stretched out after 21days, with a combined effect in the hypoxic/hyperosmotic group. Both individual and combined hyperosmotic and/or hypoxic conditions significantly upregulated SOX5, SOX9, COMP and Link-p gene expression compared with the non-induced group, and to similar levels as the TGFβ1-induced group. GAG synthesis in both hydrogel and medium was increased under hypoxic conditions, whereas hyperosmolarity decreased GAG formation in the hydrogels, but increased GAG formation in the medium. We conclude that in a joint mimicking the three-dimensional (3D) micro-environment, a combination of hyperosmolarity and hypoxia is able to induce chondrogenesis to the same extent as TGFβ1. This might lead to an interesting alternative when considering short-term triggering in a one-step surgical procedure for the treatment of cartilaginous defects.
KW - Adipose tissue-derived stem cells
KW - Chondrogenic differentiation
KW - Collagen type II
KW - Hydrogel
KW - Hyperosmolarity
KW - Hypoxia
UR - http://www.scopus.com/inward/record.url?scp=84863460563&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863460563&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/term.464
DO - https://doi.org/10.1002/term.464
M3 - Article
C2 - 21916017
SN - 1932-6254
VL - 6
SP - 570
EP - 578
JO - Journal of Tissue Engineering and Regenerative Medicine
JF - Journal of Tissue Engineering and Regenerative Medicine
IS - 7
ER -