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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Review Article

Biomaterials and Gene Therapy: A Smart Combination for MSC Musculoskeletal Engineering

Author(s): Benjamin Mesure, Patrick Menu, Jagadeesh K. Venkatesan, Magali Cucchiarini and Émilie Velot*

Volume 14, Issue 4, 2019

Page: [337 - 343] Pages: 7

DOI: 10.2174/1574888X14666181205121658

Price: $65

Abstract

Musculoskeletal pathologies, especially those affecting bones and joints, remain a challenge for regenerative medicine. The main difficulties affecting bone tissue engineering are the size of the defects, the need for blood vessels and the synthesis of appropriate matrix elements in the engineered tissue. Indeed, the cartilage is an avascular tissue and consequently has limited regenerative abilities. Thanks to their self-renewal, plasticity and immunomodulatory properties, mesenchymal stem cells (MSCs) became a central player in tissue engineering, and have already been shown to be able to differentiate towards chondrogenic or osteogenic phenotypes. Whether synthetic (e.g. tricalcium phosphate) or from natural sources (e.g. hyaluronic acid), biomaterials can be shaped to fit into bone and cartilage defects to ensure mechanical resistance and may also be designed to control cell spatial distribution or differentiation. Soluble factors are classically used to promote cell differentiation and to stimulate extracellular matrix synthesis to achieve the desired tissue production. But as they have a limited lifetime, transfection using plasmid DNA or transduction via a viral vector of therapeutic genes to induce the cell secretion of these factors allows to have more lasting effects. Also, the chondrocyte phenotype may be difficult to control over time, with for example the production of hypertrophic or osteogenic markers that is undesirable in hyaline cartilage. Thus, tissue regeneration strategies became more elaborate, with an attempt at associating the benefits of MSCs, biomaterials, and gene therapy to achieve a proper tissue repair. This minireview focuses on in vitro and in vivo studies combining biomaterials and gene therapy associated with MSCs for bone and cartilage engineering.

Keywords: Musculoskeletal lesions, MSCs, gene therapy, biomaterials, bone tissue engineering, cartilage tissue engineering.

[1]
Roux BM, Cheng M-H, Brey EM. Engineering clinically relevant volumes of vascularized bone. J Cell Mol Med 2015; 19: 903-14.
[2]
Li JP, Wang DW, Song QH. Transplantation of erythropoietin gene-transfected umbilical cord mesenchymal stem cells as a treatment for limb ischemia in rats. Genet Mol Res GMR 2015; 14: 19005-15.
[3]
Zhang JC, Zheng GF, Wu L, Ou Yang LY, Li WX. Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats. Braz J Med Biol Res Rev Bras Pesqui Medicas E Biol 2014; 47: 886-94.
[4]
Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol 2015; 11: 21-34.
[5]
Introna M, Lucchini G, Dander E, et al. Treatment of graft versus host disease with mesenchymal stromal cells: A phase I study on 40 adult and pediatric patients. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant 2014; 20: 375-81.
[6]
Jo CH, Lee YG, Shin WH, et al. Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells Dayt Ohio 2014; 32: 1254-66.
[7]
El Omar R, Beroud J, Stoltz J-F, Menu P, Velot E, Decot V. Umbilical cord mesenchymal stem cells: the new gold standard for mesenchymal stem cell-based therapies? Tissue Eng Part B Rev 2014; 20: 523-44.
[8]
Wang Q, Yang Q, Wang Z, et al. Comparative analysis of human mesenchymal stem cells from fetal-bone marrow, adipose tissue, and Warton’s jelly as sources of cell immunomodulatory therapy. Hum Vaccin Immunother 2016; 12: 85.
[9]
D’souza N, Rossignoli F, Golinelli G, et al. Mesenchymal stem/stromal cells as a delivery platform in cell and gene therapies. BMC Med [Internet]. 2015 [Cited 2018 Mar 28]; 13. Available from. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534031/
[10]
Torihashi S, Ho M, Kawakubo Y, et al. Acute and temporal expression of Tumor Necrosis Factor (TNF)-α-stimulated gene 6 product, TSG6, in mesenchymal stem cells creates microenvironments required for their successful transplantation into muscle tissue. J Biol Chem 2015; 290: 22771-81.
[11]
Chen W, Baylink DJ, Brier-Jones J, et al. PDGFB-based stem cell gene therapy increases bone strength in the mouse. Proc Natl Acad Sci USA 2015; 112: E3893-900.
[12]
Madry H, Orth P, Cucchiarini M. Gene therapy for cartilage repair. Cartilage 2011; 2: 201-25.
[13]
Beutel BG, Danna NR, Gangolli R, et al. Evaluation of bone response to synthetic bone grafting material treated with argon-based atmospheric pressure plasma. Mater Sci Eng C Mater Biol Appl 2014; 45: 484-90.
[14]
Muzzarelli RAA, El Mehtedi M, Bottegoni C, Aquili A, Gigante A. Genipin-crosslinked chitosan gels and scaffolds for tissue engineering and regeneration of cartilage and bone. Mar Drugs 2015; 13: 7314-38.
[15]
Xiao T, Guo W, Chen M, et al. Fabrication and In vitro Study of tissue-engineered cartilage scaffold derived from Wharton’s jelly extracellular matrix. BioMed Res Int 2017; 2017: 5839071.
[16]
Daly AC, Pitacco P, Nulty J, Cunniffe GM, Kelly DJ. 3D printed microchannel networks to direct vascularisation during endochondral bone repair. Biomaterials 2018; 162: 34-46.
[17]
Gonzalez-Fernandez T, Tierney EG, Cunniffe GM, O’Brien FJ, Kelly DJ. Gene delivery of TGF-β3 and BMP2 in an MSC-laden alginate hydrogel for articular cartilage and endochondral bone tissue engineering. Tissue Eng Part A 2016; 22: 776-87.
[18]
Jiang J, Fan C-Y, Zeng B-F. Experimental construction of BMP2 and VEGF gene modified tissue engineering bone in vitro. Int J Mol Sci 2011; 12: 1744-55.
[19]
Shao D, Wang C, Sun Y, Cui L. Effects of oral implants with miR-122-modified cell sheets on rat bone marrow mesenchymal stem cells. Mol Med Rep 2018; 17: 1537-44.
[20]
Li K-C, Chang Y-H, Yeh C-L, Hu Y-C. Healing of osteoporotic bone defects by baculovirus-engineered bone marrow-derived MSCs expressing MicroRNA sponges. Biomaterials 2016; 74: 155-66.
[21]
Guo P, Shi Z-L, Liu A, et al. Cartilage oligomeric matrix protein gene multilayers inhibit osteogenic differentiation and promote chondrogenic differentiation of mesenchymal stem cells. Int J Mol Sci 2014; 15: 20117-33.
[22]
Iwai R, Fujiwara M, Wakitani S, Takagi M. Ex vivo cartilage defect model for the evaluation of cartilage regeneration using mesenchymal stem cells. J Biosci Bioeng 2011; 111: 357-64.
[23]
Ikeda Y, Sakaue M, Chijimatsu R, et al. IGF-1 Gene transfer to human synovial MSCs promotes their chondrogenic differentiation potential without induction of the hypertrophic phenotype. Stem Cells Int 2017; 2017: 5804147.
[24]
Li J, Li Y, Ma S, Gao Y, Zuo Y, Hu J. Enhancement of bone formation by BMP-7 transduced MSCs on biomimetic nano-hydroxyapatite/polyamide composite scaffolds in repair of mandibular defects. J Biomed Mater Res A 2010; 95: 973-81.
[25]
Castro-Govea Y, Cervantes-Kardasch VH, Borrego-Soto G, et al. Human bone morphogenetic protein 2-transduced mesenchymal stem cells improve bone regeneration in a model of mandible distraction surgery. J Craniofac Surg 2012; 23: 392-6.
[26]
Chang SC-N, Lin T-M, Chung H-Y, et al. Large-scale bicortical skull bone regeneration using ex vivo replication-defective adenoviral-mediated bone morphogenetic protein-2 gene-transferred bone marrow stromal cells and composite biomaterials. Neurosurgery 2009; 65: 75-81. discussion 81-83.
[27]
Loozen LD, van der Helm YJM, Öner FC, Dhert WJA, Kruyt MC, Alblas J. Bone morphogenetic protein-2 nonviral gene therapy in a goat iliac crest model for bone formation. Tissue Eng Part A 2015; 21: 1672-9.
[28]
Dong S-W, Ying D-J, Duan X-J, et al. Bone regeneration using an acellular extracellular matrix and bone marrow mesenchymal stem cells expressing Cbfa1. Biosci Biotechnol Biochem 2009; 73: 2226-33.
[29]
Wang B, Huang S, Pan L, Jia S. Enhancement of bone formation by genetically engineered human umbilical cord-derived mesenchymal stem cells expressing osterix. Oral Surg Oral Med Oral Pathol Oral Radiol 2013; 116: e221-9.
[30]
Raftery RM, Mencía Castaño I, Chen G, et al. Translating the role of osteogenic-angiogenic coupling in bone formation: Highly efficient chitosan-pDNA activated scaffolds can accelerate bone regeneration in critical-sized bone defects. Biomaterials 2017; 149: 116-27.
[31]
Cao L, Liu X, Liu S, et al. Experimental repair of segmental bone defects in rabbits by angiopoietin-1 gene transfected MSCs seeded on porous β-TCP scaffolds. J Biomed Mater Res B Appl Biomater 2012; 100: 1229-36.
[32]
Cunniffe GM, Gonzalez-Fernandez T, Daly A, et al. Three-dimensional bioprinting of polycaprolactone reinforced gene activated bioinks for bone tissue engineering. Tissue Eng Part A 2017; 23: 891-900.
[33]
Cao L, Yang F, Liu G, et al. The promotion of cartilage defect repair using adenovirus mediated Sox9 gene transfer of rabbit bone marrow mesenchymal stem cells. Biomaterials 2011; 32: 3910-20.
[34]
Yang HN, Park JS, Woo DG, et al. Chondrogenesis of mesenchymal stem cells and dedifferentiated chondrocytes by transfection with SOX Trio genes. Biomaterials 2011; 32: 7695-704.
[35]
Xia W, Jin Y-Q, Kretlow JD, et al. Adenoviral transduction of hTGF-beta1 enhances the chondrogenesis of bone marrow derived stromal cells. Biotechnol Lett 2009; 31: 639-46.
[36]
He C-X, Zhang T-Y, Miao P-H, et al. TGF-β1 gene-engineered mesenchymal stem cells induce rat cartilage regeneration using nonviral gene vector. Biotechnol Appl Biochem 2012; 59: 163-9.
[37]
Li B, Yang J, Ma L, Li F, Tu Z, Gao C. Fabrication of poly(lactide-co-glycolide) scaffold filled with fibrin gel, mesenchymal stem cells, and poly(ethylene oxide)-b-poly(L-lysine)/TGF-β1 plasmid DNA complexes for cartilage restoration in vivo. J Biomed Mater Res A 2013; 101: 3097-108.
[38]
Ivkovic A, Pascher A, Hudetz D, et al. Articular cartilage repair by genetically modified bone marrow aspirate in sheep. Gene Ther 2010; 17: 779-89.
[39]
Gulotta LV, Kovacevic D, Packer JD, Deng XH, Rodeo SA. Bone marrow-derived mesenchymal stem cells transduced with scleraxis improve rotator cuff healing in a rat model. Am J Sports Med 2011; 39: 1282-9.

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