A Systematic Review of Clinical Studies Investigating Mesenchymal Stem Cells for Fracture Non-Union and Bone Defects

Abstract Background Given the limitations of current therapies for the reconstruction of bone defects, regenerative medicine has arisen as a new therapeutic strategy along with mesenchymal stem cells (MSCs), which, because of their osteogenic potential and immunomodulatory properties, have emerged as a promising alternative for the treatment of bone injuries. In vivo studies have demonstrated that MSCs have a positive effect on regeneration due to their secretion of cytokines and growth factors that, when collected in conditioned medium (MSC-CM) and applied to an injured tissue, can modulate and promote the formation of new tissue. Objective To evaluate the effectiveness of application of conditioned medium derived from mesenchymal stem cells in bone regeneration in animal and human models. Methods We conducted a systematic review with a comprehensive search through February of 2018 using several electronic databases (MEDLINE, EMBASE, SCOPUS, CENTRAL (Ovid), and LILACS), and we also used the “snowballing technique”. Articles that met the inclusion criteria were selected through abstract review and subsequent assessment of the full text. We assessed the risk of bias with the SYRCLE and Cochrane tools, and three meta-analyses were performed. Results We included 21 articles, 19 of which used animal models and 2 of which used human models. In animal models, the application of MSC-CM significantly increased the regeneration of bone defects in comparison with control groups. Human studies reported early mineralization in regenerated bones, and no bone resorption, inflammation, nor local or systemic alterations were observed in any case. The meta-analysis showed an overall favorable effect of the application of MSC-CM. Conclusions The application of MSC-CM to bone defects has a positive and favorable effect on the repair and regeneration of bone tissue, particularly in animal models. It is necessary to perform additional studies to support the application of MSC-CM in clinical practice.

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Clinical Applications of Mesenchymal Stem Cells in the Treatment of Fracture Non-Union and Bone Defects

Current Stem Cell Research & Therapy ◽

10.2174/157488812799218956 ◽

2012 ◽

Vol 7 (2) ◽

pp. 127-133 ◽

Cited By ~ 28

Author(s):

Andreas S. Shekkeris ◽

Parag K. Jaiswal ◽

Wasim S. Khan

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Defects ◽

Clinical Applications ◽

Non Union

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Periodontal regenerative medicine using mesenchymal stem cells and biomaterials: A systematic review of pre-clinical studies

Dental Materials Journal ◽

10.4012/dmj.2018-315 ◽

2019 ◽

Vol 38 (6) ◽

pp. 867-883 ◽

Cited By ~ 3

Author(s):

Sophie PORTRON ◽

Assem SOUEIDAN ◽

Anne-Claire MARSDEN ◽

Mia RAKIC ◽

Christian VERNER ◽

...

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Regenerative Medicine ◽

Clinical Studies

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Faculty Opinions recommendation of Human induced pluripotent stem cells differentiate into functional mesenchymal stem cells and repair bone defects.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726500934.793529431 ◽

2017 ◽

Author(s):

Ming Pei

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Induced Pluripotent Stem Cells ◽

Pluripotent Stem Cells ◽

Bone Defects ◽

Induced Pluripotent

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In vivo Evaluation of a Collagen Scaffold Preconditioned with Adipose-derived Mesenchymal Stem Cells Used for Bone Regeneration A histological study

Materiale Plastice ◽

10.37358/mp.18.4.5102 ◽

2018 ◽

Vol 55 (4) ◽

pp. 691-695

Author(s):

Tudor Sorin Pop ◽

Anca Maria Pop ◽

Alina Dia Trambitas Miron ◽

Klara Brinzaniuc ◽

Simona Gurzu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Histological Study ◽

Collagen Scaffold ◽

Bone Defects ◽

Collagen Scaffolds ◽

In Vivo Evaluation ◽

Calvarial Bone ◽

Bone Apposition

The use of collagen scaffolds and stem cells for obtaining a tissue-engineering complex has been an important concept in promoting repair and regeneration of the bone tissue. Such units represent important steps in the development of an ideal scaffold-cell complex that would sustain new bone apposition. The aim of our study was to perform a histologic evaluation of the healing of critical-sized bone defects, using a biologic collagen scaffold with adipose-derived mesenchymal stem cells, in comparison to negative controls created in the adjacent bone. We used 16 Wistar rats and according to the study design 2 calvarial bone defects were created in each animal, one was filled with collagen seeded with adipose-derived stem cells and the other one was considered negative control. During the following month, at weekly intervals, the animals were euthanized and the specimens from bone defects were histologically evaluated. The results showed that these scaffolds were highly biocompatible as only moderate inflammation no rejection reactions were observed. Furthermore, the first signs of osseous healing appeared after two weeks accompanied by angiogenesis. Collagen scaffolds seeded with adipose-derived mesenchymal stem cells can be considered a promising treatment option in bone regeneration of large defects.

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Regeneration of Bone Defects Using Bioactive Glass Combined with Adipose-derived Mesenchymal Stem Cells. An experimental in vivo study

Revista de Chimie ◽

10.37358/rc.19.6.7259 ◽

2019 ◽

Vol 70 (6) ◽

pp. 1983-1987

Author(s):

Cristian Trambitas ◽

Anca Maria Pop ◽

Alina Dia Trambitas Miron ◽

Dorin Constantin Dorobantu ◽

Flaviu Tabaran ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bioactive Glass ◽

Bone Repair ◽

Bone Defects ◽

Calvarial Bone ◽

Specific Protocol ◽

Repair Mechanisms ◽

Male Wistar Rats

Large bone defects are a medical concern as these are often unable to heal spontaneously, based on the host bone repair mechanisms. In their treatment, bone tissue engineering techniques represent a promising approach by providing a guide for osseous regeneration. As bioactive glasses proved to have osteoconductive and osteoinductive properties, the aim of our study was to evaluate by histologic examination, the differences in the healing of critical-sized calvarial bone defects filled with bioactive glass combined with adipose-derived mesenchymal stem cells, compared to negative controls. We used 16 male Wistar rats subjected to a specific protocol based on which 2 calvarial bone defects were created in each animal, one was filled with Bon Alive S53P4 bioactive glass and adipose-derived stem cells and the other one was considered control. At intervals of one week during the following month, the animals were euthanized and the specimens from bone defects were histologically examined and compared. The results showed that this biomaterial was biocompatible and the first signs of osseous healing appeared in the third week. Bone Alive S53P4 bioactive glass could be an excellent bone substitute, reducing the need of bone grafts.

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Mesenchymal Stem Cells in the Treatment of Cartilage Defects of the Knee: A Systematic Review of the Clinical Outcomes

The American Journal of Sports Medicine ◽

10.1177/0363546520986812 ◽

2021 ◽

pp. 036354652098681

Author(s):

Monketh Jaibaji ◽

Rawan Jaibaji ◽

Andrea Volpin

Keyword(s):

Systematic Review ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Stem Cell ◽

Mesenchymal Stem Cell ◽

Osteochondral Lesions ◽

Common Source ◽

Significant Heterogeneity ◽

Osteochondral Defects

Background: Osteochondral lesions are a common clinical problem and their management has been historically challenging. Mesenchymal stem cells have the potential to differentiate into chondrocytes and thus restore hyaline cartilage to the defect, theoretically improving clincal outcomes in these patients. They can also be harvested with minimal donor site morbidity. Purpose: To assess the clinical and functional outcomes of mesenchymal stem cell implantation to treat isolated osteochondral defects of the knee. A secondary purpose is to assess the quality of the current available evidence as well as the radiological and histological outcomes. We also reviewed the cellular preparation and operative techniques for implantation. Study Design: Systematic review. Methods: A comprehensive literature search of 4 databases was carried out: CINAHL, Embase, MEDLINE, and PubMed. We searched for clinical studies reporting the outcomes on a minimum of 5 patients with at least 12 months of follow-up. Clinical, radiological, and histological outcomes were recorded. We also recorded demographics, stem cell source, culture technique, and operative technique. Methodological quality of each study was assessed using the modified Coleman methodology score, and risk of bias for the randomized controlled studies was assessed using the Cochrane Collaboration tool. Results: Seventeen studies were found, encompassing 367 patients. The mean patient age was 35.1 years. Bone marrow was the most common source of stem cells utilized. Mesenchymal stem cell therapy consistently demonstrated good short- to medium-term outcomes in the studies reviewed with no serious adverse events being recorded. There was significant heterogeneity in cell harvesting and preparation as well as in the reporting of outcomes. Conclusion: Mesenchymal stem cells demonstrated a clinically relevant improvement in outcomes in patients with osteochondral defects of the knee. More research is needed to establish an optimal treatment protocol, long-term outcomes, and superiority over other therapies. Registration: CRD42020179391 (PROSPERO).

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