Different types of cartilage neotissue fabricated from collagen hydrogels and mesenchymal stromal cells via SOX9, TGFB1 or BMP2 gene transfer

Hydroxyapatite (HA) ceramics together with various kinds of osteogenic cells have been used in bone tissue engineering. It is well known that the ceramics structure and composition affect cell proliferation / differentiation. In this study, three different types of HA ceramics were used to investigate initial cell attachment followed by osteoblastic differentiation of human mesenchymal stromal cells (MSCs). The results indicated that micro-pore affected the cell attachment and porosity (pore diameter and inter-pore connection) was the key to allow spacious distribution of the viable cells in the ceramics. This study also confirmed that surface pore areas of HA ceramics support the differentiation of human MSCs and thus the ceramics have the capability to regenerate damaged bone tissue.

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Remodeling of Human Osteochondral Defects via rAAV-Mediated Co-Overexpression of TGF-β and IGF-I from Implanted Human Bone Marrow-Derived Mesenchymal Stromal Cells

Journal of Clinical Medicine ◽

10.3390/jcm8091326 ◽

2019 ◽

Vol 8 (9) ◽

pp. 1326

Author(s):

Stephanie Morscheid ◽

Jagadeesh Kumar Venkatesan ◽

Ana Rey-Rico ◽

Gertrud Schmitt ◽

Magali Cucchiarini

Keyword(s):

Bone Marrow ◽

Growth Factor ◽

Gene Transfer ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Human Bone ◽

Human Bone Marrow ◽

Human Model ◽

Cartilage Lesions ◽

Igf I

The application of chondrogenic gene sequences to human bone marrow-derived mesenchymal stromal cells (hMSCs) is an attractive strategy to activate the reparative activities of these cells as a means to enhance the processes of cartilage repair using indirect cell transplantation procedures that may improve the repopulation of cartilage lesions. In the present study, we examined the feasibility of co-delivering the highly competent transforming growth factor beta (TGF-β) with the insulin-like growth factor I (IGF-I) in hMSCs via recombinant adeno-associated virus (rAAV) vector-mediated gene transfer prior to implantation in a human model of osteochondral defect (OCD) ex vivo that provides a microenvironment similar to that of focal cartilage lesions. The successful co-overexpression of rAAV TGF-β/IGF-I in implanted hMSCs promoted the durable remodeling of tissue injury in human OCDs over a prolonged period of time (21 days) relative to individual gene transfer and the control (reporter lacZ gene) treatment, with enhanced levels of cell proliferation and matrix deposition (proteoglycans, type-II collagen) both in the lesions and at a distance, while hypertrophic, osteogenic, and catabolic processes could be advantageously delayed. These findings demonstrate the value of indirect, progenitor cell-based combined rAAV gene therapy to treat human focal cartilage defects in a natural environment as a basis for future clinical applications.

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Preconditioned Mesenchymal Stromal Cells to Improve Allotransplantation Outcome

Cells ◽

10.3390/cells10092325 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2325

Author(s):

Hui-Yun Cheng ◽

Madonna Rica Anggelia ◽

Cheng-Hung Lin ◽

Chih-Fan Lin

Keyword(s):

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Gene Transfection ◽

Specific Gene ◽

Multilineage Differentiation ◽

Preclinical Models ◽

Different Types ◽

Organ Tissue ◽

In Vivo Administration

Mesenchymal stromal cells (MSCs) are tissue-derived progenitor cells with immunomodulatory as well as multilineage differentiation capacities, and have been widely applied as cellular therapeutics in different disease systems in both preclinical models and clinical studies. Although many studies have applied MSCs in different types of allotransplantation, the efficacy varies. It has been demonstrated that preconditioning MSCs prior to in vivo administration may enhance their efficacy. In the field of organ/tissue allotransplantation, many recent studies have shown that preconditioning of MSCs with (1) pretreatment with bioactive factors or reagents such as cytokines, or (2) specific gene transfection, could prolong allotransplant survival and improve allotransplant function. Herein, we review these preconditioning strategies and discuss potential directions for further improvement.

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In vivo gene transfer to hematopoietic and mesenchymal stromal cells by lentiviral vector

Blood Cells Molecules and Diseases ◽

10.1016/j.bcmd.2007.10.065 ◽

2008 ◽

Vol 40 (2) ◽

pp. 278

Author(s):

Irina Nifontova ◽

Daria Svinareva ◽

Natalia Sats ◽

Vadim Surin ◽

Nina Drize

Keyword(s):

Gene Transfer ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Lentiviral Vector ◽

In Vivo Gene Transfer

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Transduction Enhancers Enable Efficient Human Adenovirus Type 5-Mediated Gene Transfer into Human Multipotent Mesenchymal Stromal Cells

Viruses ◽

10.3390/v13061136 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1136

Author(s):

Robin Nilson ◽

Olivia Lübbers ◽

Linus Weiß ◽

Karmveer Singh ◽

Karin Scharffetter-Kochanek ◽

...

Keyword(s):

Gene Transfer ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Coagulation Factor ◽

Human Adenovirus ◽

Adenovirus Type ◽

Multipotent Mesenchymal Stromal Cells ◽

Egfp Expression ◽

Migration Behavior ◽

Adenovirus Type 5

Human multipotent mesenchymal stromal cells (hMSCs) are currently developed as cell therapeutics for different applications, including regenerative medicine, immune modulation, and cancer treatment. The biological properties of hMSCs can be further modulated by genetic engineering. Viral vectors based on human adenovirus type 5 (HAdV-5) belong to the most frequently used vector types for genetic modification of human cells in vitro and in vivo. However, due to a lack of the primary attachment receptor coxsackievirus and adenovirus receptor (CAR) in hMSCs, HAdV-5 vectors are currently not suitable for transduction of this cell type without capsid modification. Here we present several transduction enhancers that strongly enhance HAdV-5-mediated gene transfer into both bone marrow- and adipose tissue-derived hMSCs. Polybrene, poly-l-lysine, human lactoferrin, human blood coagulation factor X, spermine, and spermidine enabled high eGFP expression levels in hMSCs. Importantly, hMSCs treated with enhancers were not affected in their migration behavior, which is a key requisite for many therapeutic applications. Exemplary, strongly increased expression of tumor necrosis factor (TNF)-stimulated gene 6 (TSG-6) (a secreted model therapeutic protein) was achieved by enhancer-facilitated HAdV-5 transduction. Thus, enhancer-mediated HAdV-5 vector transduction is a valuable method for the engineering of hMSCs, which can be further exploited for the development of innovative hMSC therapeutics.

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