Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial

Bajestan, Mona N.; Rajan, Archana; Edwards, Sean P.; Aronovich, Sharon; Cevidanes, Lúcia Helena Soares; Polymeri, Angeliki; Travan, Sunčica; Kaigler, Darnell

doi:10.1111/cid.12506

Cited by 64 publications

(98 citation statements)

References 33 publications

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“…The authors hypothesize that these accessory cells may serve to enhance tissue regeneration by promoting vascularization and modulating the inflammatory response in the regenerating tissues (Dennis et al., ). However, no significant differences in NBF were observed when comparing TRC‐scaffold constructs with scaffolds alone (Hernandez Alfero et al., ; Kaigler et al., , ) or AB (Bajestan et al., ).…”

Section: Discussionmentioning

confidence: 98%

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Shanbhag

Suliman

Pandis

et al. 2019

J Clinic Periodontology

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Aim The objective of the present review was to answer the focused question: what is the effect of cell therapy in terms of orofacial bone regeneration compared to grafting with only biomaterial scaffolds and/or autogenous bone? Methods Electronic databases were searched for relevant controlled clinical and pre‐clinical (large‐animal) studies. Separate meta‐analyses of quantitative data regarding histological or radiographic new bone formation were performed. Results Forty‐seven eligible clinical and 57 pre‐clinical studies were included. Clinical studies were categorized based on the use of “minimally manipulated” whole tissues (e.g., bone marrow) or ex vivo expanded cells from “uncommitted” (bone marrow, adipose tissue) or “committed” sources (periosteum, bone). Based on limited and heterogeneous clinical evidence, implantation of cells (mostly whole bone marrow), in combination with biomaterial scaffolds results in bone regeneration which is (a) superior compared to implantation of scaffolds alone in sinus and horizontal ridge augmentation, and (b) comparable to autogenous bone in alveolar cleft repair. Conclusions Although current evidence points to the benefits of cell therapy in certain clinical indications, it is unclear whether the use of ex vivo expanded cells, either uncommitted or committed, is superior to whole tissue fractions in terms of bone regeneration. The relatively larger effect sizes in favour of cell therapy observed in pre‐clinical studies are diminished in clinical trials. Future controlled studies should include cost‐effectiveness analyses to guide clinical decision‐making.

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Section: Discussionmentioning

confidence: 98%

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Shanbhag

Suliman

Pandis

et al. 2019

J Clinic Periodontology

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“…These results suggest successful clinical application in regenerating periodontal tissue, including bone tissue [41]. In alveolar cleft surgery, several clinical trials, mainly case reports, suggest promising results with the application of BMSCs, but complete reconstruction (bone fill) of extensive cleft defects has not been demonstrated [42,43]. In contrast, Hermund et al [44] showed no difference in bone density and height between a control group (graft composed of a mixture of bovine bone substitute and autologous bone particles) and a test group (same scaffold, supplemented with BMSCs that were retrieved from the tuberosity and cultivated in vitro) after maxillary sinus floor elevation.…”

Section: Sources Of Stem Cellsmentioning

confidence: 99%

Bone Tissue Regeneration in the Oral and Maxillofacial Region: A Review on the Application of Stem Cells and New Strategies to Improve Vascularization

Helder

Bravenboer

et al. 2019

Stem Cells International

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Bone tissue engineering techniques are a promising alternative for the use of autologous bone grafts to reconstruct bone defects in the oral and maxillofacial region. However, for successful bone regeneration, adequate vascularization is a prerequisite. This review presents and discusses the application of stem cells and new strategies to improve vascularization, which may lead to feasible clinical applications. Multiple sources of stem cells have been investigated for bone tissue engineering. The stromal vascular fraction (SVF) of human adipose tissue is considered a promising single source for a heterogeneous population of essential cells with, amongst others, osteogenic and angiogenic potential. Enhanced vascularization of tissue-engineered grafts can be achieved by different mechanisms: vascular ingrowth directed from the surrounding host tissue to the implanted graft, vice versa, or concomitantly. Vascular ingrowth into the implanted graft can be enhanced by (i) optimizing the material properties of scaffolds and (ii) their bioactivation by incorporation of growth factors or cell seeding. Vascular ingrowth directed from the implanted graft towards the host tissue can be achieved by incorporating the graft with either (i) preformed microvascular networks or (ii) microvascular fragments (MF). The latter may have stimulating actions on both vascular ingrowth and outgrowth, since they contain angiogenic stem cells like SVF, as well as vascularized matrix fragments. Both adipose tissue-derived SVF and MF are cell sources with clinical feasibility due to their large quantities that can be harvested and applied in a one-step surgical procedure. During the past years, important advancements of stem cell application and vascularization in bone tissue regeneration have been made. The development of engineered in vitro 3D models mimicking the bone defect environment would facilitate new strategies in bone tissue engineering. Successful clinical application requires innovative future investigations enhancing vascularization.

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“…The two studies evaluated in this systematic review produced equivocal results with one reporting improved bone formation after implantation of bone marrow stromal stem cells (Dallari et al., ) and one report failing to find any such effect (Liebergall et al., ). A recent study investigating the use of bone marrow stem cells for the regeneration of alveolar cleft and trauma in adults found that while the use of these cells is safe, their ability to facilitate complete regeneration of large alveolar defects is limited (Bajestan et al., ). Most recently, significant regeneration (in both horizontal and vertical dimensions) for severe mandibular resorption has been reported when bone marrow stromal stem cells were used in conjunction with biphasic calcium phosphate scaffolds and titanium‐reinforced membranes (Gjerde et al., ).…”

Section: Mesenchymal Stem Cells and Bone Regenerationmentioning

confidence: 99%

Mesenchymal stem cells and biologic factors leading to bone formation

Bartold

Gronthos

Haynes

et al. 2019

J Clinic Periodontology

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Background Physiological bone formation and bone regeneration occurring during bone repair can be considered distinct but similar processes. Mesenchymal stem cells (MSC) and associated biologic factors are crucial to both bone formation and bone regeneration. Aim To perform a narrative review of the current literature regarding the role of MSC and biologic factors in bone formation with the aim of discussing the clinical relevance of in vitro and in vivo animal studies. Methods The literature was searched for studies on MSC and biologic factors associated with the formation of bone in the mandible and maxilla. The search specifically targeted studies on key aspects of how stem cells and biologic factors are important in bone formation and how this might be relevant to bone regeneration. The results are summarized in a narrative review format. Results Different types of MSC and many biologic factors are associated with bone formation in the maxilla and mandible. Conclusion Bone formation and regeneration involve very complex and highly regulated cellular and molecular processes. By studying these processes, new clinical opportunities will arise for therapeutic bone regenerative treatments.

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Stem cell therapy for reconstruction of alveolar cleft and trauma defects in adults: A randomized controlled, clinical trial

Cited by 64 publications

References 33 publications

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

Bone Tissue Regeneration in the Oral and Maxillofacial Region: A Review on the Application of Stem Cells and New Strategies to Improve Vascularization

Mesenchymal stem cells and biologic factors leading to bone formation

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