Evaluation of adult equine bone marrow‐ and adipose‐derived progenitor cell chondrogenesis in hydrogel cultures

Abstract

Bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived progenitor cells (ADPCs) are potential alternatives to autologous chondrocytes for cartilage resurfacing strategies. In this study, the chondrogenic potentials of these cell types were compared by quantifying neo-tissue synthesis and assaying gene expression and accumulation of extracellular matrix (ECM) components of cartilage. Adult equine progenitor cells encapsulated in agarose or selfassembling peptide hydrogels were cultured in the presence or absence of TGFb1 for 3 weeks. In BM-MSCs-seeded hydrogels, TGFb1 stimulated ECM synthesis and accumulation 3-41-fold relative to TGFb1-free culture. In ADPC cultures, TGFb1 stimulated a significant increase in ECM synthesis and accumulation in peptide (18-29-fold) but not agarose hydrogels. Chromatographic analysis of BM-MSC-seeded agarose and peptide hydrogels cultured in TGFb1 medium showed extensive synthesis of aggrecan-like proteoglycan monomers. ADPCs seeded in peptide hydrogel also synthesized aggrecan-like proteoglycans, although to a lesser extent than seen in BM-MSC hydrogels, whereas aggrecan-like proteoglycan synthesis in ADPC-seeded agarose was minimal. RT-PCR analysis of TGFb1 cultures showed detectable levels of type II collagen gene expression in BM-MSC but not ADPC cultures. Histological analysis of TGFb1-cultured peptide hydrogels showed the deposition of a continuous proteoglycan-and type II collagen rich ECM for BM-MSCs but not ADPCs. Therefore, this study showed both protein and gene expression evidence of superior chondrogenesis of BM-MSCs relative to ADPCs. ß

Transient Exposure to Transforming Growth Factor Beta 3 Improves the Mechanical Properties of Mesenchymal Stem Cell–Laden Cartilage Constructs in a Density-Dependent Manner

“…We have recently developed high-throughput screening methods to identify and optimize new small-molecule mediators of chondrogenesis. We and others have also deployed novel materials 55,56 and constructed mechanical loading systems 57,58 that may better fosterthechondrogenicdifferentiation process.Theseadvances have the potential to generate functional cartilage replacements based on MSCs, especially if combined with the defined media regimes and seeding density requirements indicated from our results. Recent work using chondrocyte-based constructs demonstrate that mechanical loading applied in concert with transient exposure to TGF-b3 can generate neotissues with mechanical properties exceeding that of either treatment alone.…”

Tissue engineering and cartilage

“…34 In a study examining the difference in chondrogenic potential of bone marrow and adipose stem cells on two different hydrogels, agarose and self-assembling peptide, it was found that bone marrow MSCs had an increased production of ECM in the presence of TGFβ and the peptide hydrogel was a better host than was agarose. 35 Poly-lactic glycolic acid (PLGA) is a synthetic material that has excellent biocompatibility and biodegradability. Chitosan is a substance extracted from natural sources and also has excellent biocompatibility and is used in wound healing.…”

Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling

“…[20][21][22][23][24] Benefits have been demonstrated for the use of these peptide hydrogels in cartilage, 25,26 liver, 27 and cardiovascular 28,29 tissues, and they have been shown to provide a microenvironment that enhances the chondrogenesis of BMSCs. 26,30 These peptides can also control the delivery and release of functional proteins, 21 therapeutic macromolecules, 22 and bioactive motifs. 20 Taken together, these studies suggest the potential to co-encapsulate growth factors and BMSCs in self-assembling peptide hydrogels to generate cartilage neotissue.…”