Histologic and Immunohistochemical Characteristics of Failed Articular Cartilage Resurfacing Procedures for Osteochondritis of the Knee

LaPrade, Robert F.; Bursch, Laura S.; Olson, Erik J.; Havlas, Vojtěch; Carlson, Cathy S.

doi:10.1177/0363546507308359

Cited by 84 publications

(73 citation statements)

References 28 publications

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“…Patients treated with intra-articular hyaluronic acid injections (IA-HA) show clear symptomatic improvement and the intervention appears cost effective in up to 2 years of follow-up [8], but whether cartilage regeneration actually occurs is open to debate [9]. Neither autologous chondrocyte implantation nor microdrilling alone seems to result in cartilage resurfacing histologically resembling normal articular cartilage [10].…”

Section: Introductionmentioning

confidence: 99%

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

et al. 2017

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“…Alternatively, ACs have been harvested directly from patients and used for tissue generation ex vivo, despite their limited capacity to proliferate. Tissue generated by passaged chondrocytes exhibits fibrocartilage characteristics and can improve the quality of life for the patient in the short term but ultimately undergoes degradation as it lacks sufficient weight-bearing capacity (LaPrade et al, 2008;Tins et al, 2005). Pluripotent stem cells (PSCs) [embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] represent a novel and potentially unlimited source of chondrocytes and tissues for therapeutic applications as these cells are able to generate a broad spectrum of cell types under appropriate conditions in vitro.…”

Section: Introductionmentioning

confidence: 99%

Specification of chondrocytes and cartilage tissues from embryonic stem cells

et al. 2013

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SUMMARYOsteoarthritis primarily affects the articular cartilage of synovial joints. Cell and/or cartilage replacement is a promising therapy, provided there is access to appropriate tissue and sufficient numbers of articular chondrocytes. Embryonic stem cells (ESCs) represent a potentially unlimited source of chondrocytes and tissues as they can generate a broad spectrum of cell types under appropriate conditions in vitro. Here, we demonstrate that mouse ESC-derived chondrogenic mesoderm arises from a Flk-1 -/Pdgfrα + (F -P + ) population that emerges in a defined temporal pattern following the development of an early cardiogenic F -P + population. Specification of the late-arising F -P + population with BMP4 generated a highly enriched population of chondrocytes expressing genes associated with growth plate hypertrophic chondrocytes. By contrast, specification with Gdf5, together with inhibition of hedgehog and BMP signaling pathways, generated a population of non-hypertrophic chondrocytes that displayed properties of articular chondrocytes. The two chondrocyte populations retained their hypertrophic and non-hypertrophic properties when induced to generate spatially organized proteoglycan-rich cartilage-like tissue in vitro. Transplantation of either type of chondrocyte, or tissue generated from them, into immunodeficient recipients resulted in the development of cartilage tissue and bone within an 8-week period. Significant ossification was not observed when the tissue was transplanted into osteoblast-depleted mice or into diffusion chambers that prevent vascularization. Thus, through stage-specific manipulation of appropriate signaling pathways it is possible to efficiently and reproducibly derive hypertrophic and non-hypertrophic chondrocyte populations from mouse ESCs that are able to generate distinct cartilage-like tissue in vitro and maintain a cartilage tissue phenotype within an avascular and/or osteoblast-free niche in vivo.

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“…Short of total joint replacement, current clinical practices for cartilage repair include microfracture (broaching the subchondral bone interface to allow stem cells to access the wound site from the marrow) or delivery of exogenously expanded autologous chondrocytes (autologous chondrocyte implantation; ACI) (Vijayan et al, 2010). In both cases, limited defect size, fragile fibrocartilaginous repair tissue and long recovery periods reduce efficacy and widespread application (LaPrade et al, 2008;Nehrer et al, 1999;Van Assche et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells produce functional cartilage matrix in three-dimensional culture in regions of optimal nutrient supply

Farrell

Comeau²,

Mauck³

2012

eCM

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Mesenchymal stem cells (MSCs) are a promising cell source for the treatment of musculoskeletal disease. However, MSC chondrogenesis in 3D culture generates constructs whose macroscopic (bulk) mechanical properties are inferior to constructs formed with chondrocytes. To investigate where and why these deficits in functionality arise, we assessed the local (microscopic) properties of cell-laden hydrogel constructs. Both chondrocyte-and MSC-laden constructs showed pronounced depth dependency, with ~3.5 and ~11.5 fold decreases in modulus from the surface to central regions, respectively. Importantly, in the surface region, properties were similar, suggesting that MSCs can produce matrix of mechanical equivalence to chondrocytes, but only in conditions of maximal nutrient support. Dynamic culture on an orbital shaker (which enhances diffusion) attenuated depth-dependent disparities in mechanics and improved the bulk properties compared to free swelling conditions (225 to 438 kPa for chondrocytes, 122 to 362 kPa for MSCs). However, properties in MSC-based constructs remained significantly lower due to persistent mechanical deficits in central regions. MSC viability in these central regions decreased markedly, with these changes apparent as early as day 21, while chondrocyte viability remained high. These findings suggest that, under optimal nutrient conditions, MSCs can undergo chondrogenesis and form functional tissue on par with that of the native tissue cell type. However, the lack of viability and matrix production in central regions suggests that chondrogenic MSCs do not yet fully recapitulate the advanced phenotype of the chondrocyte, a cell that is optimized to survive (and thrive) in a mechanically challenging and nutrient-poor environment.

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Histologic and Immunohistochemical Characteristics of Failed Articular Cartilage Resurfacing Procedures for Osteochondritis of the Knee

Abstract: The histologic appearance of the repair tissue of 3 different failed articular cartilage resurfacing procedures was similar and did not resemble normal articular cartilage.

Cited by 84 publications

References 28 publications

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

Specification of chondrocytes and cartilage tissues from embryonic stem cells

Mesenchymal stem cells produce functional cartilage matrix in three-dimensional culture in regions of optimal nutrient supply

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