Human Oral Stem Cells, Biomaterials and Extracellular Vesicles: A Promising Tool in Bone Tissue Repair

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Abstract

Tissue engineering and/or regenerative medicine are fields of life science exploiting both engineering and biological fundamentals to originate new tissues and organs and to induce the regeneration of damaged or diseased tissues and organs. In particular, de novo bone tissue regeneration requires a mechanically competent osteo-conductive/inductive 3D biomaterial scaffold that guarantees the cell adhesion, proliferation, angiogenesis and differentiation into osteogenic lineage. Cellular components represent a key factor in tissue engineering and bone growth strategies take advantage from employment of mesenchymal stem cells (MSCs), an ideal cell source for tissue repair. Recently, the application of extracellular vesicles (EVs), isolated from stem cells, as cell-free therapy has emerged as a promising therapeutic strategy. This review aims at summarizing the recent and representative research on the bone tissue engineering field using a 3D scaffold enriched with human oral stem cells and their derivatives, EVs, as a promising therapeutic potential in the reconstructing of bone tissue defects.

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Tissue-engineered bone regeneration.

H Petite, V Viateau, W Bensaïd … (2000)

Bone lesions above a critical size become scarred rather than regenerated, leading to nonunion. We have attempted to obtain a greater degree of regeneration by using a resorbable scaffold with regeneration-competent cells to recreate an embryonic environment in injured adult tissues, and thus improve clinical outcome. We have used a combination of a coral scaffold with in vitro-expanded marrow stromal cells (MSC) to increase osteogenesis more than that obtained with the scaffold alone or the scaffold plus fresh bone marrow. The efficiency of the various combinations was assessed in a large segmental defect model in sheep. The tissue-engineered artificial bone underwent morphogenesis leading to complete recorticalization and the formation of a medullary canal with mature lamellar cortical bone in the most favorable cases. Clinical union never occurred when the defects were left empty or filled with the scaffold alone. In contrast, clinical union was obtained in three out of seven operated limbs when the defects were filled with the tissue-engineered bone.

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Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway

Jieyuan Zhang, Xiaolin Liu, Haiyan Li … (2016)

Background Recently, accumulating evidence has shown that exosomes, the naturally secreted nanocarriers of cells, can exert therapeutic effects in various disease models in the absence of parent cells. However, application of exosomes in bone defect repair and regeneration has been rarely reported, and little is known regarding their underlying mechanisms. Methods Exosomes derived from human-induced pluripotent stem cell-derived mesenchymal stem cells (hiPS-MSC-Exos) were combined with tricalcium phosphate (β-TCP) to repair critical-sized calvarial bone defects, and the efficacy was assessed by histological examination. We evaluated the in vitro effects of hiPSC-MSC-Exos on the proliferation, migration, and osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs) by cell-counting, scratch assays, and qRT-PCR, respectively. Gene expression profiling and bioinformatics analyses were also used to identify the underlying mechanisms in the repair. Results We found that the exosome/β-TCP combination scaffolds could enhance osteogenesis as compared to pure β-TCP scaffolds. In vitro assays showed that the exosomes could release from β-TCP and could be internalized by hBMSCs. In addition, the internalization of exosomes into hBMSCs could profoundly enhance the proliferation, migration, and osteogenic differentiation of hBMSCs. Furthermore, gene expression profiling and bioinformatics analyses demonstrated that exosome/β-TCP combination scaffolds significantly altered the expression of a network of genes involved in the PI3K/Akt signaling pathway. Functional studies further confirmed that the PI3K/Akt signaling pathway was the critical mediator during the exosome-induced osteogenic responses of hBMSCs. Conclusions We propose that the exosomes can enhance the osteoinductivity of β-TCP through activating the PI3K/Akt signaling pathway of hBMSCs, which means that the exosome/β-TCP combination scaffolds possess better osteogenesis activity than pure β-TCP scaffolds. These results indicate that naturally secreted nanocarriers-exosomes can be used as a bioactive material to improve the bioactivity of the biomaterials, and that hiPS-MSC-Exos combined with β-TCP scaffolds can be potentially used for repairing bone defects. Electronic supplementary material The online version of this article (doi:10.1186/s13287-016-0391-3) contains supplementary material, which is available to authorized users.

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The Horizon of Materiobiology: A Perspective on Material-Guided Cell Behaviors and Tissue Engineering.

Changsheng Liu, Yin Xiao, Yulin LI (2017)

Although the biological functions of cell and tissue can be regulated by biochemical factors (e.g., growth factors, hormones), the biophysical effects of materials on the regulation of biological activity are receiving more attention. In this Review, we systematically summarize the recent progress on how biomaterials with controllable properties (e.g., compositional/degradable dynamics, mechanical properties, 2D topography, and 3D geometry) can regulate cell behaviors (e.g., cell adhesion, spreading, proliferation, cell alignment, and the differentiation or self-maintenance of stem cells) and tissue/organ functions. How the biophysical features of materials influence tissue/organ regeneration have been elucidated. Current challenges and a perspective on the development of novel materials that can modulate specific biological functions are discussed. The interdependent relationship between biomaterials and biology leads us to propose the concept of "materiobiology", which is a scientific discipline that studies the biological effects of the properties of biomaterials on biological functions at cell, tissue, organ, and the whole organism levels. This Review highlights that it is more important to develop ECM-mimicking biomaterials having a self-regenerative capacity to stimulate tissue regeneration, instead of attempting to recreate the complexity of living tissues or tissue constructs ex vivo. The principles of materiobiology may benefit the development of novel biomaterials providing combinative bioactive cues to activate the migration of stem cells from endogenous reservoirs (i.e., cell niches), stimulate robust and scalable self-healing mechanisms, and unlock the body's innate powers of regeneration.

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Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 09 October 2019

Publication date Collection: October 2019

Volume: 20

Issue: 20

Electronic Location Identifier: 4987

Affiliations

[1 ]Department of Medical, Oral and Biotechnological Sciences, University “G. d’Annunzio” Chieti-Pescara, 66100 Chieti, Italy; guya.marconi@ 123456unich.it (G.D.M.); sante.pierdomenico@ 123456unich.it (S.D.P.); adriano.piattelli@ 123456unich.it (A.P.); francesca.diomede@ 123456unich.it (F.D.); jacopo.pizzicannella@ 123456unich.it (J.P.)

[2 ]ASL02 Lanciano-Vasto-Chieti, Ss. Annunziata Hospital, 66100 Chieti, Italy

Author notes

[* ]Correspondence: trubiani@ 123456unich.it ; Tel.: +39-0871-3554097

[†]

These authors contributed equally to this work.

Author information

Oriana Trubiani https://orcid.org/0000-0002-7459-4898

Francesca Diomede https://orcid.org/0000-0002-0384-6509

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Publisher ID: ijms-20-04987

DOI: 10.3390/ijms20204987

PMC ID: 6834314

PubMed ID: 31600975

SO-VID: 10b31430-3d7c-4c19-af40-2dfc94786a93

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

History

Date received : 26 July 2019

Date accepted : 04 October 2019

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Bacterial extracellular vesicles

Most cited references 60

Tissue-engineered bone regeneration.

Exosomes/tricalcium phosphate combination scaffolds can enhance bone regeneration by activating the PI3K/Akt signaling pathway

The Horizon of Materiobiology: A Perspective on Material-Guided Cell Behaviors and Tissue Engineering.

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