Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus

Cucchiarini, Magali; McNulty, Amy L.; Mauck, Robert L.; Setton, Lori A.; Guilak, Farshid; Madry, Henning

doi:10.1016/j.joca.2016.03.018

Cited by 42 publications

(26 citation statements)

References 101 publications

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“…Stable vectors are required because of the long residence times in vivo. These treatments typically involve doses of 100-1000 mL with a virus density of at least Gene therapy is currently used in ongoing clinical trials for the treatment of cancer [8], hereditary diseases [9], infectious diseases such as HIV infection [10,11] and tissue engineering [12]. The replication of the virus particle must be inactivated to ensure that the vector itself does not cause a disease.…”

Section: Vectors For Gene Therapymentioning

confidence: 99%

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Grein¹,

Weidner²,

Czermak³

2017

New Insights Into Cell Culture Technology

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The industrial-scale manufacturing of viruses or virus-like particles in cell culture is necessary for gene therapy and the treatment of cancer with oncolytic viruses. Complex multistep processes are required in both cases, but the low virus titers in batch cultures and the temperature sensitivity of the virus particles limit the production scale. To meet commercial and regulatory requirements, each process must be scalable and reproducible and must yield high virus titers. These requirements are met by establishing a cell culture process that matches the properties of the virus/host-cell system and by using serum-free cell culture medium. This chapter focuses on two case studies to consider the different aspects of process design, such as the reactor configuration and operational mode: the continuous production of retroviral pseudotype vectors in a retroviral packaging cell line and the production of oncolytic measles virus vectors for cancer therapy.

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Section: Vectors For Gene Therapymentioning

confidence: 99%

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Grein¹,

Weidner²,

Czermak³

2017

New Insights Into Cell Culture Technology

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“…However, these studies did not intend to focus on the anisotropy or heterogeneity associated with its ECM nanostructure. Without such knowledge, it is challenging to connect the meniscus disease etiology and pathogenesis with its structural complexity [26], or to design biomaterials that can replicate the functions of native tissue [27]. …”

Section: Introductionmentioning

confidence: 99%

Micromechanical anisotropy and heterogeneity of the meniscus extracellular matrix

Han

et al. 2017

Acta Biomaterialia

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To understand how the complex biomechanical functions of the meniscus are endowed by the nanostructure of its extracellular matrix (ECM), we studied the anisotropy and heterogeneity in the micromechanical properties of the meniscus ECM. We used atomic force microscopy (AFM) to quantify the time-dependent mechanical properties of juvenile bovine meniscus at deformation length scales corresponding to the diameters of collagen fibrils. At this scale, anisotropy in the elastic modulus of the circumferential fibers, the major ECM structural unit, can be attributed to differences in fibril deformation modes: uncrimping when normal to the fiber axis, and laterally constrained compression when parallel to the fiber axis. Heterogeneity among different structural units is mainly associated with their variations in microscale fiber orientation, while heterogeneity across anatomical zones is due to alterations in collagen fibril diameter and alignment at the nanoscale. Unlike the elastic modulus, the time-dependent properties are more homogeneous and isotropic throughout the ECM. These results enable a detailed understanding of the meniscus structure-mechanics at the nanoscale, and can serve as a benchmark for understanding meniscus biomechanical function, documenting disease progression and designing tissue repair strategies.

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“…Cell-based therapies represent an alternative approach to repair meniscus tears (18, 19) or for engineering meniscus implants (1, 20). However, our present knowledge of heterogeneous meniscus cell populations that inhabit and maintain this complex tissue is incomplete.…”

Section: Introductionmentioning

confidence: 99%

Relevance of meniscal cell regional phenotype to tissue engineering

Grogan

Pauli

Lotz

et al. 2017

Connective Tissue Research

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Purpose Meniscus contains heterogeneous populations of cells that have not been fully characterized. Cell phenotype is often lost during culture; however, culture expansion is typically required for tissue engineering. We examined and compared cell surface molecule expression levels on human meniscus cells from the vascular and avascular regions and articular chondrocytes while documenting changes during culture-induced dedifferentiation. Materials and Methods Expression of 16 different surface molecules were examined by flow cytometry after monolayer culture for 24 h, 1 week, and 2 weeks. Menisci were also immunostained to document the spatial distributions of selected surface molecules. Results Meniscus cells and chondrocytes exhibited several similarities in surface molecule profiles with dynamic changes during culture. A greater percentage of meniscal cells were positive for CD14, CD26, CD49c, and CD49f compared to articular chondrocytes. Initially, more meniscal cells from the vascular region were positive for CD90 compared to cells from the avascular region or chondrocytes. Cells from the vascular region also expressed higher levels of CD166 and CD271 compared to cells from the avascular region. CD90, CD166, and CD271-positive cells were predominately perivascular in location. However, CD166-positive cells were also located in the superficial layer and in the adjacent synovial and adipose tissue. Conclusions These surface marker profiles provide a target phenotype for differentiation of progenitors in tissue engineering. The spatial location of progenitor cells in meniscus is consistent with higher regenerative capacity of the vascular region, while the surface progenitor subpopulations have potential to be utilized in tears created in the avascular region.

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Advances in combining gene therapy with cell and tissue engineering-based approaches to enhance healing of the meniscus

Cited by 42 publications

References 101 publications

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Concepts for the Production of Viruses and Viral Vectors in Cell Cultures

Micromechanical anisotropy and heterogeneity of the meniscus extracellular matrix

Relevance of meniscal cell regional phenotype to tissue engineering

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