Efficacy of autologous stem cells for bone regeneration during endosseous dental implants insertion - A systematic review of human studies

Abstract

Availability of adequate quantity and quality of bone is prerequisite for longevity and survival of endosseous dental implants. Most of the clinicians face with the problem of lack of bone due to long-standing edentulism during this treatment modality. Conventional therapies with the use of various types of bone grafts and membranes have provided clinicians with unpredictable and compromised results. Cell-based therapies utilizing undifferentiated cells, that have the potential to differentiate into various cell types including osteoblastic lineages, have demonstrated through various previously conducted in-vitro and animal studies, a successful formation of bone in a predictable manner. Thus the main objective of this review was to evaluate the effectiveness of these therapies when applied on human subjects.

A search was carried out in MEDLINE (via PubMed) and Cochrane CENTRAL databases for completed randomized and non-randomised clinical trials utilizing stem cell-based therapies with histologic and radiographic analysis written in English up to January 2019. This search of the literature yielded 10 studies meeting the inclusion and exclusion criteria. In all these studies, stem cells were primarily used to achieve bone augmentation during insertion of endosseous dental implants. Results of these therapies conducted on human subjects have shown a positive impact on bone regeneration, in particular, therapies utilizing bone marrow and adipose tissue derived stem cells. But the clinicians need to examine the efficacy, safety, feasibility of these therapies while treating large size defects or planning for shorter healing period and early loading of dental implants.

Introduction

Replacing lost teeth with endosseous dental implants is a widely-accepted treatment modality among patients, clinicians and academicians.1, 2, 3 It has been long known that among those who desire to undergo endosseous implant therapy, a substantial number lack adequate amount of bone.⁴ This condition happen as a result of jaw defects, loss of teeth or teeth being congenitally absent. As a result, alveolar bone of the jaw is not subjected to the functional stimulus inherently generated by the teeth and their supporting structures and, thus leading to, further resorption of bone.⁵ This combined effect results in severe horizontal and vertical bone deficiencies and insufficient volume of bone to reconstruct these areas of the jaw with functional and esthetic tooth replacements.⁶

Bone regeneration in the oral and maxillofacial region after its loss, due to various causes as mentioned above, continues to be a challenge and its reconstruction still depends mainly up on employing additive treatments modalities through application of large autogenous grafts, allografts, xenografts, and synthetic alloplastic materials.⁷

In bone reconstruction procedures, autologous bone is presently considered as the gold standard. In this procedure, autologous bone is harvested from the patient and transplanted to the defect site by surgeons.⁸ However, this procedure has numerous severe drawbacks like procuring of graft requires a second surgical site and generates only meager bone stock, the two-stage procedure prolongs surgery time and patients frequently suffer from pain and damage at the donor's site. Furthermore, autologous bone has an unpredictable resorption rate.9, 10, 11 All these factors increase patient discomfort and treatment costs.

To overcome the limitations of these conventional therapies, a newer, more targeted, cell and tissue-based therapies are required.^12,13 Stem cell therapies provides a promising tissue engineering strategy to enhance tissue regeneration and to boost de novo formation of both soft and hard tissues.13, 14, 15, 16

In the medical and dental specialities, concepts of tissue-engineering therapy, is extensively being used to regenerate the function of lost or damaged tissues. This tissue-engineering therapy relies on a triad, which incorporates cells with regenerative capacity (i.e., stem cells), signalling molecules such as growth factors, and a biocompatible matrix serving as a scaffold.¹⁷ In the field of dentistry, cell-based therapy has been used for rehabilitation of the craniofacial and the temporomandibular complexes,¹⁸ regeneration of the pulpal,¹⁹ and periodontal tissues^20,21 and bone regeneration.²²

Cell-based therapies utilize undifferentiated cells which are either embryonic stem cells that originates in blastocysts or adult stem cells located in adult tissues like bone marrow.²³ Mesenchymal stem cells (MSCs) are multipotent adult stem cells with distinct biologic characteristics which are most commonly related to their mesodermal lineage (adipogenic, chondrogenic, osteogenic, or myogenic).²⁴ So these MSCs being non-hematopoietic progenitor cells can differentiate into various mesenchymal cell lineages, including osteoblastic lineages. Thus, MSCs provide clinicians with a viable option to various bone graft materials for the regeneration of bone, particularly during placement of dental implants.

Many systematic reviews and meta-analysis have analyzed the efficacies of MSCs for the regeneration of bone in intra-oral sites through pre-clinical animal studies25, 26, 27 and many of them have reported these stem cells to be a promising alternative compared to traditional therapies. But there are almost no reviews conducted till now to demonstrate their efficacies on human subjects. So this systematic review was conducted to find out the effectiveness of stem cell therapies in the regeneration of bone in human subjects during the insertion of dental implants.