Abstract

Cell therapy strategies using mesenchymal stem cells (MSCs) carried in fibrin glue have shown promising results in regenerative medicine. MSCs are crucial for tissue healing because they have angiogenic, anti-apoptotic and immunomodulatory properties, in addition to the ability to differentiate into several specialized cell lines. Fibrin sealant or fibrin glue is a natural polymer involved in the coagulation process. Fibrin glue provides a temporary structure that favors angiogenesis, extracellular matrix deposition and cell-matrix interactions. Additionally, fibrin glue maintains the local and paracrine functions of MSCs, providing tissue regeneration through less invasive clinical procedures. Thus, the objective of this systematic review was to assess the potential of fibrin glue combined with MSCs in bone or cartilage regeneration. The bibliographic search was performed in the PubMed/MEDLINE, LILACS and Embase databases, using the descriptors (“fibrin sealant” OR “fibrin glue”) AND “stem cells” AND “bone regeneration”, considering articles published until 2021. In this case, 12 preclinical and five clinical studies were selected to compose this review, according to the eligibility criteria. In preclinical studies, fibrin glue loaded with MSCs, alone or associated with bone substitute, significantly favored bone defects regeneration compared to scaffold without cells. Similarly, fibrin glue loaded with MSCs presented considerable potential to regenerate joint cartilage injuries and multiple bone fractures, with significant improvement in clinical parameters and absence of postoperative complications. Therefore, there is clear evidence in the literature that fibrin glue loaded with MSCs, alone or combined with bone substitute, is a promising strategy for treating lesions in bone or cartilaginous tissue.

Highlights

  • Advances in regenerative medicine have brought new therapeutic approaches to treat chronic injuries or to regenerate tissues with limited capacity for spontaneous regeneration, such as bone tissue [1]

  • The results showed that fibrin glue loaded with mesenchymal stem cells (MSCs) showed considerable potential to regenerate the cartilaginous tissue of the joint, with significant improvement in painful symptoms and in the clinical parameters [44–47]

  • While the bone substitute improves the mechanical properties of the scaffold, fibrin glue facilitates the fixation of the graft and promotes better adhesion of the MSCs at the injury site [31–33,35,37,38,43]. Considering these issues, some preclinical studies included in this review evaluated the effect of fibrin glue loaded with MSCs and mixed with bone substitute, such as demineralized bone [32,35,37] and type II collagen hydrogel [38]

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Summary

Introduction

Advances in regenerative medicine have brought new therapeutic approaches to treat chronic injuries or to regenerate tissues with limited capacity for spontaneous regeneration, such as bone tissue [1]. Stem cells (SCs) have been used successfully for presenting characteristics that are essential to promote tissue regeneration, such as self-renewal capacity and potential for differentiation in specialized cell lines. Embryonic stem cells (ESCs) are pluripotent and have the ability to differentiate into most specialized cells in the organism. Ethical issues limit the use of ESCs in clinical practice. To address this question, recent strategies have investigated the regenerative potential of induced pluripotent stem cells (iPSCs), obtained by reprogramming somatic cells through the regulation of transcription factors. MSCs are capable of self-renewal, proliferation and differentiation in some specialized cell lines, such as osteoblasts, chondroblasts and adipocytes (Figure 2) [5,7,8]. MSCs presents adherent growth on culture plastic and can be characterized by the expression of specific surface antigens, such as CD90, CD73, CD29 and CD105 [1,5,7,8]

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