scholarly journals Application of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets for Periodontal Regeneration

2019 ◽  
Vol 20 (11) ◽  
pp. 2796 ◽  
Author(s):  
Satoru Onizuka ◽  
Takanori Iwata
Keyword(s):  
Dental Implants ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Clinical Studies ◽  
Periodontal Ligament ◽  
Alveolar Bone ◽  
Periodontal Regeneration ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Inflammatory Disorder ◽  
Barrier Membranes

Periodontitis is a chronic inflammatory disorder that causes destruction of the periodontal attachment apparatus including alveolar bone, the periodontal ligament, and cementum. Dental implants have been routinely installed after extraction of periodontitis-affected teeth; however, recent studies have indicated that many dental implants are affected by peri-implantitis, which progresses rapidly because of the failure of the immune system. Therefore, there is a renewed focus on periodontal regeneration aroundnatural teeth. To regenerate periodontal tissue, many researchers and clinicians have attempted to perform periodontal regenerative therapy using materials such as bioresorbable scaffolds, growth factors, and cells. The concept of guided tissue regeneration, by which endogenous periodontal ligament- and alveolar bone-derived cells are preferentially proliferated by barrier membranes, has proved effective, and various kinds of membranes are now commercially available. Clinical studies have shown the significance of barrier membranes for periodontal regeneration; however, the technique is indicated only for relatively small infrabony defects. Cytokine therapies have also been introduced to promote periodontal regeneration, but the indications are also for small size defects. To overcome this limitation, ex vivo expanded multipotent mesenchymal stromal cells (MSCs) have been studied. In particular, periodontal ligament-derived multipotent mesenchymal stromal cells are thought to be a responsible cell source, based on both translational and clinical studies. In this review, responsible cell sources for periodontal regeneration and their clinical applications are summarized. In addition, recent transplantation strategies and perspectives about the cytotherapeutic use of stem cells for periodontal regeneration are discussed.

scholarly journals Proteomic Profiling of the Human Fetal Multipotent Mesenchymal Stromal Cells Secretome

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5283
Author(s):  
Arseniy A. Lobov ◽  
Natalia M. Yudintceva ◽  
Alexey G. Mittenberg ◽  
Sergey V. Shabelnikov ◽  
Natalia A. Mikhailova ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Biomedical Applications ◽  
Alveolar Bone ◽  
Shotgun Proteomics ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Proliferative Potential ◽  
Proteomic Profiling ◽  
The Common ◽  
Early Human

Secretome of multipotent mesenchymal stromal cells (MSCs) is actively used in biomedical applications such as alveolar bone regeneration, treatment of cardiovascular disease, and neurodegenerative disorders. Nevertheless, hMSCs have low proliferative potential and production of the industrial quantity of their secretome might be challenging. Human fetal multipotent mesenchymal stromal cells (FetMSCs) isolated from early human embryo bone marrow are easy to expand and might be a potential source for pharmaceutical substances production based on their secretome. However, the secretome of FetMSCs was not previously analyzed. Here, we describe the secretome of FetMSCs using LC-MALDI shotgun proteomics. We identified 236 proteins. Functional annotation of the identified proteins revealed their involvement in angiogenesis, ossification, regulation of apoptosis, and immune response processes, which made it promising for biomedical applications. The proteins identified in the FetMSCs secretome are involved in the same biological processes as proteins from previously described adult hMSCs secretomes. Nevertheless, many of the common hMSCs secretome components (such as VEGF, FGF, Wnt and TGF-β) have not been identified in the FetMSCs secretome.

scholarly journals RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes

2020 ◽  
Author(s):  
Satoru Onizuka ◽  
Yasuharu Yamazaki ◽  
Sung-Joon Park ◽  
Takayuki Sugimoto ◽  
Yumiko Sone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Periodontal Ligament ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Human Mscs ◽  
Minimum Criteria

Abstract Background Multipotent mesenchymal stromal cells (MSCs) can be isolated from numerous tissues and are attractive candidates for therapeutic clinical applications due to their immunomodulatory and pro-regenerative capacity. Although the minimum criteria for defining MSCs have been defined, their characteristics are known to vary depending on their tissue of origin.Results We isolated and characterized human MSCs from three different bones (ilium (I-MSCs), maxilla (Mx-MSCs) and mandibular (Md-MSCs)) and proceeded with next generation RNA-sequencing. Furthermore, to investigate the gene expression profiles among other cell types, we obtained RNA-seq data of human embryonic stem cells (ESCs) and several types of MSCs (periodontal ligament-derived MSCs, bone marrow-derived MSCs, and ESCs-derived MSCs) from the Sequence Reads Archive and analyze the transcriptome profile. We found that MSCs derived from tissues of the maxillofacial region, such as the jaw bone and periodontal ligament, were HOX-negative, while those derived from other tissues were HOX-positive. We also identified that MSX1, LHX8, and BARX1 , an essential regulator of craniofacial development, were strongly expressed in maxillofacial tissue-derived MSCs. Although MSCs may be divided into two distinct groups, the cells originated from over the neck or not, on the basis of differences in gene expression profile, the expression patterns of all CD antigen genes were similar among different type of MSCs, except for ESCs.Conclusions Our findings suggest that MSCs from different anatomical locations, despite meeting general characterization criteria, have remarkable differences in gene expression and positional memory. Although stromal cells from different anatomical sources are generally categorized as MSCs, their differentiation potential and biological functions vary. We suggested that MSCs may retain an original tissue memory about the developmental process, including gene expression profiles. This could have an important impact when choosing an appropriate cell source for regenerative therapy using MSCs.

Collection and culture of alveolar bone marrow multipotent mesenchymal stromal cells from older individuals

2009 ◽  
Vol 107 (6) ◽  
pp. 1198-1204 ◽  
Author(s):  
Juan Han ◽  
Hironori Okada ◽  
Hideki Takai ◽  
Youhei Nakayama ◽  
Takahide Maeda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Alveolar Bone ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Older Individuals

scholarly journals EFFICIENCY OF THE COMBINATION BASED ON BONE AUGMENTATION MATERIALS AND MULTIPOTENT MESENCHYMAL STROMAL CELLS OF ADIPOSE TISSUE IN PATIENTS OF STUDY GROUPS BEFORE DENTAL IMPLANTATION

2021 ◽  
Vol 20 (1) ◽  
pp. 11-17
Author(s):  
Andri Bambuliak ◽  
Nataliia Kuzniak ◽  
Roman Dmytrenko ◽  
Lesia Lopushniak ◽  
Oleg Boichuk
Keyword(s):  
Adipose Tissue ◽  
Bone Tissue ◽  
Dental Implants ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Study Groups ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Bone Augmentation ◽  
Group I ◽  
Group Ii

In recent decades, the most common method of treating partial or complete adentia is the use of dental implants. Often, due to insufficient jaw bone volume due to atrophy in the are of the removed teeth, it is impossible to perform intraosseous implantation. In order to eliminate the defi cit of bone tissue before the installation of dental implants, surgical interventions are required. Examination and treatment with dental implants were performed on 140 patients who had previously undergone surgery and used bone augmentation materials and their combinations with multipotent mesenchymal stromal cells of adipose tissue to increase the volume of jaw bone tissue. 3 months after the installation of dental implants in patients of group I, in which the restoration of the volume of bone tissue of the jaws was performed using bone augmentation material «Colapan–L», and in persons of group II, where augmentation was used a combination of drug «Colapan–L», multipotent mesenchymal stromal cells of adipose tissue and platelet-rich plasma, the values of the OHI–S index corresponded to the data before treatment, p>0.05, and were equal to each other, p2>0.05. In the control group III, the values of this index increased 1.4 times relative to baseline, p <0.05, and were signifi cantly higher than in patients of groups I and II, p1<0.01. After 3 months of observation, a decrease in the PMA index data relative to baseline values was determined: 1.2 times in group I, p, p1 <0.01, and 1.1 times in group II, p <0.05, p1, p2<0,01. At the same time, in patients of group III the values of this parameter increased and were 1.3 times higher than the reference values, p <0.01. After 6 months of studies in patients of groups I and III, the values of the SchillerPisarev test were higher than the initial data, p<0.05, and were equal to each other, p1>0.05. In patients of group II, the values of this parameter were equal to the initial data, p>0.05, and were probably lower data in persons of groups I and III, p1, p2<0.01. It was found that in patients in whom a combination based on multipotent mesenchymal stromal cells of adipose tissue, the drug «Colapan–L» and platelet- enriched blood plasma was used to fi ll bone defects, peri-implant tissues were completely restored after dental implants. The effectiveness of our proposed osteoplastic combination in patients of the study groups was confi rmed by the positive dynamics of the values of the hygienic index OHI-S, periodontal index PMA and Schiller- Pisarev test during the observation. 

scholarly journals RNA-sequencing reveals positional memory of multipotent mesenchymal stromal cells from oral and maxillofacial tissue transcriptomes

2020 ◽  
Author(s):  
Satoru Onizuka ◽  
Yasuharu Yamazaki ◽  
Sung-Joon Park ◽  
Takayuki Sugimoto ◽  
Yumiko Sone ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Sequencing ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Periodontal Ligament ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Human Mscs ◽  
Minimum Criteria

Abstract Background Multipotent mesenchymal stromal cells (MSCs) can be isolated from numerous tissues and are attractive candidates for therapeutic clinical applications due to their immunomodulatory and pro-regenerative capacity. Although the minimum criteria for defining MSCs have been defined, their characteristics are known to vary depending on their tissue of origin.Results We isolated and characterized human MSCs from three different bones (ilium (I-MSCs), maxilla (Mx-MSCs) and mandibular (Md-MSCs)) and proceeded with next generation RNA-sequencing. Furthermore, to investigate the gene expression profiles among other cell types, we obtained RNA-seq data of human embryonic stem cells (ESCs) and several types of MSCs (periodontal ligament-derived MSCs, bone marrow-derived MSCs, and ESCs-derived MSCs) from the Sequence Reads Archive and analyze the transcriptome profile. We found that MSCs derived from tissues of the maxillofacial region, such as the jaw bone and periodontal ligament, were HOX-negative, while those derived from other tissues were HOX-positive. We also identified that MSX1, LHX8, and BARX1 , an essential regulator of craniofacial development, were strongly expressed in maxillofacial tissue-derived MSCs. Although MSCs may be divided into two distinct groups, the cells originated from over the neck or not, on the basis of differences in gene expression profile, the expression patterns of all CD antigen genes were similar among different type of MSCs, except for ESCs.Conclusions Our findings suggest that MSCs from different anatomical locations, despite meeting general characterization criteria, have remarkable differences in gene expression and positional memory. Although stromal cells from different anatomical sources are generally categorized as MSCs, their differentiation potential and biological functions vary. We suggested that MSCs may retain an original tissue memory about the developmental process, including gene expression profiles. This could have an important impact when choosing an appropriate cell source for regenerative therapy using MSCs.

scholarly journals Multipotent mesenchymal stromal cells are sensitive to thermic stress – potential implications for therapeutic hyperthermia

2020 ◽  
Vol 37 (1) ◽  
pp. 430-441
Author(s):  
Alexander Rühle ◽  
Andreas Thomsen ◽  
Rainer Saffrich ◽  
Maren Voglstätter ◽  
Birgit Bieber ◽  
...  
Keyword(s):  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Therapeutic Hyperthermia

scholarly journals Interleukin-1β Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces

2021 ◽  
Vol 22 (3) ◽  
pp. 1027
Author(s):  
Christian Behm ◽  
Michael Nemec ◽  
Alice Blufstein ◽  
Maria Schubert ◽  
Xiaohui Rausch-Fan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Periodontal Ligament ◽  
Induced Expression ◽  
Gene And Protein Expression ◽  
Tensile Strains ◽  
Orthodontic Forces ◽  
Low Magnitude

The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of MMPs and TIMPs is influenced by the aseptic inflammation occurring during orthodontic treatment. Interleukin (IL)-1β is one of the most abundant inflammatory mediators in this process and crucially affects the expression of MMPs and TIMPs in the presence of cyclic low-magnitude orthodontic tensile forces. In this study we aimed to investigate, for the first time, how IL-1β induced expression of MMPs, TIMPs and how IL-1β in hPDL-MSCs was changed after applying in vitro low-magnitude orthodontic tensile strains in a static application mode. Hence, primary hPDL-MSCs were stimulated with IL-1β in combination with static tensile strains (STS) with 6% elongation. After 6- and 24 h, MMP-1, MMP-2, TIMP-1 and IL-1β expression levels were measured. STS alone had no influence on the basal expression of investigated target genes, whereas IL-1β caused increased expression of these genes. In combination, they increased the gene and protein expression of MMP-1 and the gene expression of MMP-2 after 24 h. After 6 h, STS reduced IL-1β-induced MMP-1 synthesis and MMP-2 gene expression. IL-1β-induced TIMP-1 gene expression was decreased by STS after 6- and 24-h. At both time points, the IL-1β-induced gene expression of IL-1β was increased. Additionally, this study showed that fetal bovine serum (FBS) caused an overall suppression of IL-1β-induced expression of MMP-1, MMP-2 and TIMP-1. Further, it caused lower or opposite effects of STS on IL-1β-induced expression. These observations suggest that low-magnitude orthodontic tensile strains may favor a more inflammatory and destructive response of hPDL-MSCs when using a static application form and that this response is highly influenced by the presence of FBS in vitro.

scholarly journals 3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Diego Noé Rodríguez-Sánchez ◽  
Giovana Boff Araujo Pinto ◽  
Luciana Politti Cartarozzi ◽  
Alexandre Leite Rodrigues de Oliveira ◽  
Ana Livia Carvalho Bovolato ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sciatic Nerve ◽  
Nerve Injury ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Multipotent Mesenchymal Stromal Cells ◽  
Sciatic Nerve Injury ◽  
Motor Deficits ◽  
3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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