Matrix-directed differentiation of human adipose derived mesenchymal stem cells to dermal-like fibroblasts that produce extracellular matrix
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Date
2015-04
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JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
Abstract
Commercially available skin substitutes lack essential non-immune cells for adequate tissue regeneration
of non-healing wounds. A tissue-engineered, patient-specific, dermal substitute could be an
attractive option for regenerating chronic wounds, for which adipose-derived mesenchymal stem cells
(ADMSCs) could become an autologous source. However, ADMSCs are multipotent in nature and may
differentiate into adipocytes, osteocytes and chondrocytes in vitro, and may develop into undesirable
tissues upon transplantation. Therefore, ADMSCs committed to the fibroblast lineage could be a better
option for in vitro or in vivo skin tissue engineering. The objective of this study was to standardize
in vitro culture conditions for ADMSCs differentiation into dermal-like fibroblasts which can synthesize
extracellular matrix (ECM) proteins. Biomimetic matrix composite, deposited on tissue culture polystyrene
(TCPS), and differentiationmedium(DM), supplemented with fibroblast-conditioned medium and
growth factors,were used as a fibroblast-specific niche (FSN) for cell culture. For controls, ADMSCswere
cultured on bare TCPS with either DM or basal medium (BM). Culture of ADMSCs on FSN upregulated
the expression of differentiation markers such as fibroblast-specific protein-1 (FSP-1) and a panel of
ECM molecules specific to the dermis, such as fibrillin-1, collagen I, collagen IV and elastin. Immunostaining
showed the deposition of dermal-specific ECM,which was significantly higher in FSN compared
to control. Fibroblasts derived from ADMSCs can synthesize elastin, which is an added advantage for
successful skin tissue engineering as compared to fibroblasts fromskin biopsy. To obtain rapid differentiation
of ADMSCs to dermal-like fibroblasts for regenerative medicine, a matrix-directed differentiation
strategy may be employed. Copyright © 2014 John Wiley & Sons, Ltd
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Keywords
extracellular matrix; autologous stem cells; adipose-derived mesenchymal stem cells; skin tissue engineering; dermal tissue regeneration; chronic wounds; differentiation; dermal fibroblasts
Citation
Unnikrishnan S, Jayakumar K, Krishnan LK. Matrix-directed differentiation of human adipose derived mesenchymal stem cells to dermal-like fibroblasts that produce extracellular matrix. JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE. 2014