Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment

Wu, Shun-Cheng; Chang, Je-Ken; Wang, Chih-Kuang; Wang, Gwo-Jaw; Ho, Mei-Ling

doi:10.1016/j.biomaterials.2009.09.089

Cited by 109 publications

(107 citation statements)

References 56 publications

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“…Studies have shown that stem-cell interactions with HA promote expression of chondrogenic markers including COL2, AGG, and Sox 9 (32,33). In this study, blocking the hMSC-HA interactions using antibodies specifically targeting CD44 or CD168 significantly down-regulated the expression of major chondrogenic markers, confirming the importance of receptor-mediated HA interactions in chondrogenesis.…”

Section: Discussionsupporting

confidence: 76%

Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis

Bian

Guvendiren

Mauck

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

364

300

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Methacrylated hyaluronic acid (HA) hydrogels provide a backbone polymer with which mesenchymal stem cells (MSCs) can interact through several cell surface receptors that are expressed by MSCs, including CD44 and CD168. Previous studies showed that this 3D hydrogel environment supports the chondrogenesis of MSCs, and here we demonstrate through functional blockade that these specific cell-material interactions play a role in this process. Beyond matrix interactions, cadherin molecules, a family of transmembrane glycoproteins, play a critical role in tissue development during embryogenesis, and N-cadherin is a key factor in mediating cellcell interactions during mesenchymal condensation and chondrogenesis. In this study, we functionalized HA hydrogels with Ncadherin mimetic peptides and evaluated their role in regulating chondrogenesis and cartilage matrix deposition by encapsulated MSCs. Our results show that conjugation of cadherin peptides onto HA hydrogels promotes both early chondrogenesis of MSCs and cartilage-specific matrix production with culture, compared with unmodified controls or those with inclusion of a scrambled peptide domain. This enhanced chondrogenesis was abolished via treatment with N-cadherin-specific antibodies, confirming the contribution of these N-cadherin peptides to chondrogenesis. Subcutaneous implantation of MSC-seeded constructs also showed superior neocartilage formation in implants functionalized with N-cadherin mimetic peptides compared with controls. This study demonstrates the inherent biologic activity of HA-based hydrogels, as well as the promise of biofunctionalizing HA hydrogels to emulate the complexity of the natural cell microenvironment during embryogenesis, particularly in stem cell-based cartilage regeneration.M esenchymal stem cells (MSCs) have emerged as a clinically relevant cell source for regenerative medicine due to their potential to differentiate into several mesenchymal lineages including cartilage, bone, and fat (1, 2). The multipotent differentiation of MSCs is tightly regulated by both soluble and physical cues present in the pericellular microenvironment, including cell-cell and cell-matrix interactions, cues that can be engineered into a variety of natural and synthetic biomaterial scaffolds (3). These materials may be either permissive to chondrogenesis (inert materials including agarose and PEG) or inductive to chondrogenesis by mimicking components of the natural pericellular microenvironment (4, 5). For example, photopolymerizable hydrogels composed of methacrylated (Me) hyaluronic acid (HA) may provide biological cues such as CD44 and CD168 interactions based on the role of HA in cellular signaling (6-8) (Fig. 1). Coincident with the onset of condensation and the first appearance of cartilage in the embryo is the appearance of specific binding sites for HA on bud limb mesenchymal cells (9). Large HA molecules are involved in the aggregation of these cells during condensation via multivalent cross-bridging (10), and HA has already been shown to enhan...

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Section: Discussionsupporting

confidence: 76%

Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis

Bian

Guvendiren

Mauck

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

364

300

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mentioning

confidence: 99%

“…An appropriate microenvironment is helpful for maintaining MSC survival, commitment, and differentiation (6,35). Our previous report also showed that a hyaluronan-enriched microenvironment can both initiate and promote the chondrogenic differentiation of human adipose-derived stem cells (ADSCs) (35). In this study, we further hypothesized that under chondrogenic induction, PEMF and single-pulse electromagnetic field (SPEMF) stimulation may promote chondrogenic differentiation and cartilaginous matrix formation of MSCs, and that combined treatment with chondrogenic inductive factor and EMFs may be used for articular cartilage tissue engineering.…”

mentioning

confidence: 99%

Electromagnetic fields enhance chondrogenesis of human adipose-derived stem cells in a chondrogenic microenvironment in vitro

Lin

et al. 2013

Journal of Applied Physiology

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“…Yoo et al [80] immobilized hyaluronic acid onto macroporous PLGA scaffolds to enhance the attachment of chondrocytes as well as the synthesis of GAG and collagen compared to unmodified PLGA scaffolds. Human adipose derived stem cells cultured on hyaluronic acid-modified PLGA scaffolds expressed higher levels of chondrogenic marker genes and increased in the production of sulphated GAG and collagen II, as compared to those cultured in unmodified PLGA scaffolds at 4 weeks [81].…”

Section: Biomaterialsmentioning

confidence: 95%

Nanomaterials for cartilage tissue engineering

Chiu¹,

Waldman²

2016

Nanomaterials and Regenerative Medicine

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Enhancement of chondrogenesis of human adipose derived stem cells in a hyaluronan-enriched microenvironment

Cited by 109 publications

References 56 publications

Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis

Hydrogels that mimic developmentally relevant matrix and N-cadherin interactions enhance MSC chondrogenesis

Electromagnetic fields enhance chondrogenesis of human adipose-derived stem cells in a chondrogenic microenvironment in vitro

Nanomaterials for cartilage tissue engineering

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