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Papers by Jeanine Hendriks

ICMS Annual Symposium 2021, 2021

The American Journal of Sports Medicine, 2020

Background: There is an unmet need for a single-stage cartilage repair treatment that is cost-eff... more Background: There is an unmet need for a single-stage cartilage repair treatment that is cost-effective and chondrocyte-based. Purpose: To evaluate the safety and preliminary efficacy of autologous freshly isolated primary chondrocytes and bone marrow mononucleated cells (MNCs) seeded into a PolyActive scaffold in patients with symptomatic cartilage lesions of the knee. Study Design: Case series; Level of evidence, 4. Methods: A total of 40 patients with symptomatic knee cartilage lesions were treated with freshly isolated autologous chondrocytes combined with bone marrow MNCs delivered in a biodegradable load-bearing scaffold. The treatment requires only 1 surgical intervention and is potentially a cost-effective alternative to autologous chondrocyte implantation. The primary chondrocytes and bone marrow MNCs were isolated, washed, counted, mixed, and seeded into a load-bearing scaffold in the operating room. Patients were followed up at 3, 6, 12, 18, and 24 months. Primary endpoin...

Introduction: INSTRUCT (CellCoTec B.V., Netherlands) is a technology that combines freshly isolat... more Introduction: INSTRUCT (CellCoTec B.V., Netherlands) is a technology that combines freshly isolated autologous chondrocytes and mono-nucleated cells from bone marrow with a porous scaffold filling the defect and providing cartilage matching mechanical stability. Based on (pre-)clinical data it is anticipated[for full text, please go to the a.m. URL]

Tissues are complex 3-dimensional structures with a highly organized architecture made up of cell... more Tissues are complex 3-dimensional structures with a highly organized architecture made up of cells and matrix. The cells and matrix in a tissue are continuously interacting with each other and (cells from) their surrounding tissues to maintain their form and function. Interactions of cells with their surrounding cells and matrix are equally important for a successful repair reaction. While in tissue engineering significant progress has been made, still a number of challenges need to be overcome for the development of clinically applicable treatments.

The present invention relates in one aspect to the use of a matrix gel comprising chondrocytes or... more The present invention relates in one aspect to the use of a matrix gel comprising chondrocytes or progenitor cells thereof in a density below that of natural cartilage as a cartilage repair implant wherein said cells exhibit increases production of extracellular matrix material.

The invention relates to the field of medical science, in particular to technology directed at re... more The invention relates to the field of medical science, in particular to technology directed at repairing defects in living, preferably human, tissue. The present invention provides a method for inducing differentiation of multipotent cells to a desired cell type, as well as a method for repairing a tissue defect in a human or animal patient using the concept of said method for inducing differentiation of multipotent cells. The invention further relates to a kit for carrying out the method for repairing a tissue defect.

A source of cells with chondrogenic potential for clinical application is mesenchymal stem cells ... more A source of cells with chondrogenic potential for clinical application is mesenchymal stem cells (MSCs) from bone marrow (1,2). Differentiation of multipotent MSCs is in general initiated at high-cell density in 3-D with a combination of chondrogenic growth factors (3,4). We examined the potential of primary articular chondrocytes (PACs) to enhance matrix production when mixed with MSCs at different ratios in vitro in a pellet model and in vivo as seeded onto 3D-printed PEGT/PBT block co-polymer scaffolds, in a nude mouse model. Results described here demonstrate that co-culturing in vitro or co–implantation in vivo of primary chondrocytes with mesenchymal stem cells enhances cartilage specific matrix production.

The invention relates to a method for isolating cells from a tissue sample. In preferred embodime... more The invention relates to a method for isolating cells from a tissue sample. In preferred embodiments, chondrocytes are isolated from cartilage tissue in a shorter time than hitherto considered possible.

MRS Proceedings, 2006

ABSTRACT3D fibrous scaffolds with shell-core fiber architecture offer the possibility to create m... more ABSTRACT3D fibrous scaffolds with shell-core fiber architecture offer the possibility to create multifunctional structures. In this study, a construct that combines mechanical stability with the core polymer and optimal surface properties for cell-material interactions with the shell polymer is discussed. Scaffolds were fabricated by a rapid prototyped technique known as 3D Fiber Deposition (3DF) and used for cartilage tissue engineering. Cells maintained the typical rounded morphology of cartilage in the shell-core scaffolds, while they spread into a spindle-like shape in scaffolds fabricated with the core polymer only. Extracellular matrix production and an increase in the dynamic stiffness of the engineered construct revealed a progressive maturation of the formed tissue, suggesting that shell-core 3D scaffolds could be optimal for cartilage tissue engineering.

Tissue Engineering Part C: Methods, 2015

Enzymatic isolation of chondrocytes from a cartilage biopsy is the first step to establish in vit... more Enzymatic isolation of chondrocytes from a cartilage biopsy is the first step to establish in vitro models of chondrogenesis or to generate cell-based grafts for cartilage repair. Such process is based on manually operated procedures and typically results in yields lower than 20% of the total available cells. In this study, we hypothesized that, as compared to conventionally used protocols, the enzymatic digestion of human articular cartilage in the presence of ascorbic acid 2-phosphate (AscA2P) or of sodium chloride (NaCl), in combination with the use of a perfusion bioreactor system, leads to a higher and more reproducible yield of cell populations with high proliferation and chondrogenic capacity. The addition of AscA2P within the enzymatic digestion medium did not significantly increase the cell yield, but resulted in a significant decrease of the intradonor variability in cell yield (-17.8%±10.7%, p=0.0247) and in a significant increase of the proliferation rate of the isolated chondrocytes (+19.0%±1.4%, p<0.05) with respect to the control group. The addition of NaCl during cartilage digestion did not modulate cell yield. When the cartilage digestion was further performed under direct perfusion flow, beneficial synergistic effects were achieved, with an overall increase of 34.7%±6.8% (p<0.001) in the cell yield and an average decrease of 57.8%±11.2% (p<0.01) in the coefficient of variation with respect to the control group. Importantly, by implementing this strategy it was possible to retrieve clonal subpopulations more efficiently capable of undergoing chondrogenesis, both in vitro and in vivo. Our findings bear relevance for the preparation of human chondrocytes for laboratory investigations, and in the perspective of efficient and streamlined manufacturing of cell/tissue grafts for articular cartilage repair.

Stem cells translational medicine, 2014

Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both youn... more Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge of the consequences of these diseases and the exponential growth in research of regenerative medicine have given rise to different treatment types. Of these, cell-based treatments are increasingly applied because they have the potential to regenerate cartilage, treat symptoms, and ultimately prevent or delay OA. Although these approaches give promising results, they require a costly in vitro cell culture procedure. The answer may lie in single-stage procedures that, by using cell combinations, render in vitro expansion redundant. In the last two decades, cocultures of cartilage cells and a variety of (mesenchymal) stem cells have shown promising results as different studies report cartil...

ICMS Annual Symposium 2021, 2021

The American Journal of Sports Medicine, 2020

Background: There is an unmet need for a single-stage cartilage repair treatment that is cost-eff... more Background: There is an unmet need for a single-stage cartilage repair treatment that is cost-effective and chondrocyte-based. Purpose: To evaluate the safety and preliminary efficacy of autologous freshly isolated primary chondrocytes and bone marrow mononucleated cells (MNCs) seeded into a PolyActive scaffold in patients with symptomatic cartilage lesions of the knee. Study Design: Case series; Level of evidence, 4. Methods: A total of 40 patients with symptomatic knee cartilage lesions were treated with freshly isolated autologous chondrocytes combined with bone marrow MNCs delivered in a biodegradable load-bearing scaffold. The treatment requires only 1 surgical intervention and is potentially a cost-effective alternative to autologous chondrocyte implantation. The primary chondrocytes and bone marrow MNCs were isolated, washed, counted, mixed, and seeded into a load-bearing scaffold in the operating room. Patients were followed up at 3, 6, 12, 18, and 24 months. Primary endpoin...

Introduction: INSTRUCT (CellCoTec B.V., Netherlands) is a technology that combines freshly isolat... more Introduction: INSTRUCT (CellCoTec B.V., Netherlands) is a technology that combines freshly isolated autologous chondrocytes and mono-nucleated cells from bone marrow with a porous scaffold filling the defect and providing cartilage matching mechanical stability. Based on (pre-)clinical data it is anticipated[for full text, please go to the a.m. URL]

Tissues are complex 3-dimensional structures with a highly organized architecture made up of cell... more Tissues are complex 3-dimensional structures with a highly organized architecture made up of cells and matrix. The cells and matrix in a tissue are continuously interacting with each other and (cells from) their surrounding tissues to maintain their form and function. Interactions of cells with their surrounding cells and matrix are equally important for a successful repair reaction. While in tissue engineering significant progress has been made, still a number of challenges need to be overcome for the development of clinically applicable treatments.

The present invention relates in one aspect to the use of a matrix gel comprising chondrocytes or... more The present invention relates in one aspect to the use of a matrix gel comprising chondrocytes or progenitor cells thereof in a density below that of natural cartilage as a cartilage repair implant wherein said cells exhibit increases production of extracellular matrix material.

The invention relates to the field of medical science, in particular to technology directed at re... more The invention relates to the field of medical science, in particular to technology directed at repairing defects in living, preferably human, tissue. The present invention provides a method for inducing differentiation of multipotent cells to a desired cell type, as well as a method for repairing a tissue defect in a human or animal patient using the concept of said method for inducing differentiation of multipotent cells. The invention further relates to a kit for carrying out the method for repairing a tissue defect.

A source of cells with chondrogenic potential for clinical application is mesenchymal stem cells ... more A source of cells with chondrogenic potential for clinical application is mesenchymal stem cells (MSCs) from bone marrow (1,2). Differentiation of multipotent MSCs is in general initiated at high-cell density in 3-D with a combination of chondrogenic growth factors (3,4). We examined the potential of primary articular chondrocytes (PACs) to enhance matrix production when mixed with MSCs at different ratios in vitro in a pellet model and in vivo as seeded onto 3D-printed PEGT/PBT block co-polymer scaffolds, in a nude mouse model. Results described here demonstrate that co-culturing in vitro or co–implantation in vivo of primary chondrocytes with mesenchymal stem cells enhances cartilage specific matrix production.

The invention relates to a method for isolating cells from a tissue sample. In preferred embodime... more The invention relates to a method for isolating cells from a tissue sample. In preferred embodiments, chondrocytes are isolated from cartilage tissue in a shorter time than hitherto considered possible.

MRS Proceedings, 2006

ABSTRACT3D fibrous scaffolds with shell-core fiber architecture offer the possibility to create m... more ABSTRACT3D fibrous scaffolds with shell-core fiber architecture offer the possibility to create multifunctional structures. In this study, a construct that combines mechanical stability with the core polymer and optimal surface properties for cell-material interactions with the shell polymer is discussed. Scaffolds were fabricated by a rapid prototyped technique known as 3D Fiber Deposition (3DF) and used for cartilage tissue engineering. Cells maintained the typical rounded morphology of cartilage in the shell-core scaffolds, while they spread into a spindle-like shape in scaffolds fabricated with the core polymer only. Extracellular matrix production and an increase in the dynamic stiffness of the engineered construct revealed a progressive maturation of the formed tissue, suggesting that shell-core 3D scaffolds could be optimal for cartilage tissue engineering.

Tissue Engineering Part C: Methods, 2015

Enzymatic isolation of chondrocytes from a cartilage biopsy is the first step to establish in vit... more Enzymatic isolation of chondrocytes from a cartilage biopsy is the first step to establish in vitro models of chondrogenesis or to generate cell-based grafts for cartilage repair. Such process is based on manually operated procedures and typically results in yields lower than 20% of the total available cells. In this study, we hypothesized that, as compared to conventionally used protocols, the enzymatic digestion of human articular cartilage in the presence of ascorbic acid 2-phosphate (AscA2P) or of sodium chloride (NaCl), in combination with the use of a perfusion bioreactor system, leads to a higher and more reproducible yield of cell populations with high proliferation and chondrogenic capacity. The addition of AscA2P within the enzymatic digestion medium did not significantly increase the cell yield, but resulted in a significant decrease of the intradonor variability in cell yield (-17.8%±10.7%, p=0.0247) and in a significant increase of the proliferation rate of the isolated chondrocytes (+19.0%±1.4%, p<0.05) with respect to the control group. The addition of NaCl during cartilage digestion did not modulate cell yield. When the cartilage digestion was further performed under direct perfusion flow, beneficial synergistic effects were achieved, with an overall increase of 34.7%±6.8% (p<0.001) in the cell yield and an average decrease of 57.8%±11.2% (p<0.01) in the coefficient of variation with respect to the control group. Importantly, by implementing this strategy it was possible to retrieve clonal subpopulations more efficiently capable of undergoing chondrogenesis, both in vitro and in vivo. Our findings bear relevance for the preparation of human chondrocytes for laboratory investigations, and in the perspective of efficient and streamlined manufacturing of cell/tissue grafts for articular cartilage repair.

Stem cells translational medicine, 2014

Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both youn... more Cartilage damage and osteoarthritis (OA) impose an important burden on society, leaving both young, active patients and older patients disabled and affecting quality of life. In particular, cartilage injury not only imparts acute loss of function but also predisposes to OA. The increase in knowledge of the consequences of these diseases and the exponential growth in research of regenerative medicine have given rise to different treatment types. Of these, cell-based treatments are increasingly applied because they have the potential to regenerate cartilage, treat symptoms, and ultimately prevent or delay OA. Although these approaches give promising results, they require a costly in vitro cell culture procedure. The answer may lie in single-stage procedures that, by using cell combinations, render in vitro expansion redundant. In the last two decades, cocultures of cartilage cells and a variety of (mesenchymal) stem cells have shown promising results as different studies report cartil...