Hyaluronan initiates chondrogenesis mainly via CD44 in human adipose-derived stem cells

Abstract

Cell-matrix adhesion is one of the important interactions that regulates stem cell survival, self-renewal, and differentiation. Our previous report (Wu SC, Chang JK, Wang CK, Wang GJ, Ho ML. Biomaterials 31: 631-640, 2010) indicated that a microenvironment enriched with hyaluronan (HA) initiated and enhanced chondrogenesis in human adipose-derived stem cells (hADSCs). We further hypothesize that HA-induced chondrogenesis in hADSCs is mainly due to the interaction of HA and CD44 (HA-CD44), a cell surface receptor of HA. The HA-CD44 interaction was tested by examining the mRNA expression of hyaluronidase-1 (Hyal-1) and chondrogenic marker genes (SOX-9, collagen type II, and aggrecan) in hADSCs cultured on HA-coated wells. Cartilaginous matrix formation, sulfated glycosaminoglycan, and collagen productions by hADSCs affected by HA-CD44 interaction were tested in a three-dimensional fibrin hydrogel. About 99.9% of hADSCs possess CD44. The mRNA expressions of Hyal-1 and chondrogenic marker genes were upregulated by HA in hADSCs on HA-coated wells. Blocking HA-CD44 interaction by anti-CD44 antibody completely inhibited Hyal-1 expression and reduced chondrogenic marker gene expression, which indicates that HA-induced chondrogenesis in hADSCs mainly acts through HA-CD44 interaction. A 2-h preincubation and coculture of cells with HA in hydrogel (HA/fibrin hydrogel) not only assisted in hADSC survival, but also enhanced expression of Hyal-1 and chondrogenic marker genes. Higher levels of sulfated glycosaminoglycan and total collagen were also found in HA/fibrin hydrogel group. Immunocytochemistry showed more collagen type II, but less collagen type X, in HA/fibrin than in fibrin hydrogels. Our results indicate that signaling triggered by HA-CD44 interaction significantly contributes to HA-induced chondrogenesis and may be applied to adipose-derived stem cell-based cartilage regeneration.

Enhanced Chondrogenic Differentiation of Dental Pulp Stem Cells Using Nanopatterned PEG-GelMA-HA Hydrogels

“…5,51,52 A previous study has shown that signaling triggered by binding of CD44 to HA is important for chondrogenesis as blocking with anti-CD44 antibodies inhibited chondrogenesis in adipose-derived stem cells. 53 Thus, the increased membrane-localized CD44 staining in cells on PEG-GelMA-HA scaffolds may indicate that CD44 is binding to HA and this binding triggers signaling for chondrogenic induction.…”

The cell‐engineered construct of cartilage on the basis of biopolymer hydrogel matrix and human adipose tissue‐derived mesenchymal stromal cells (in vitro study)

“…Among natural polymer hydrogels for tissue‐engineered cartilage development are collagen I and II, hyaluronan, fibrin glue, alginate, chitosan, gelatin etc . A quantitative in vitro accumulation of the cartilage matrix has been demonstrated histologically, immunohistochemically, and biochemically for chondrocytes and MSCs from different sources, cultured in collagen, hyaluronan, chitosan, alginate, fibrin, and self‐assembling peptides . Most of these matrices also support neocartilage matrix deposition in vivo when implanted into nude mice …”

“…It has been proven that human adipose‐derived mesenchymal stromal cells (hADSCs) are adhesive, have a fibroblast‐like morphology, express multiple CD marker antigens satisfying MSCs phenotype and possess multilineage potential to differentiate in mesenchymal lineages . Several previous studies have shown that hADSCs undergo chondrogenesis and deposit a cartilage‐specific matrix in pellet cultures and in a variety of natural and synthetic scaffold materials in the presence of the appropriate growth factors …”

PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies

“…Since CD44 is overexpressed in tumor cells and plays a key role in metastasis, targeting CD44 with HA-covered particles has demonstrated a great potential to improve drug delivery [13]. CD44 is also expressed in articular cells and involved in matrix attachment and signal transduction [14,15]. HA is a major component of extracellular matrix and synovial fluid and is internalized by chondrocytes through CD44 binding [16].…”